Tuesday, 28 June 2022

Modalities for Treatment of Pain

       Modalities for Treatment of Pain


                                        DR KS Dhillon

The International Association for the Study of Pain (IASP) has defined pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage” [1]. There are two broad categories of pain;

  • Somatic Pain: This result from the activation of nociceptors that are sensitive to noxious stimuli in cutaneous or deep tissues. The pain experienced is described as constant, aching, and gnawing. 
  • Visceral Pain: This is also mediated by nociceptors. The pain is described as deep, aching, and colicky. It is poorly localized and often referred to cutaneous sites, which may be tender. 

The five most common types of pain include:

  • Acute pain
  • Chronic pain
  • Neuropathic pain
  • Nociceptive pain
  • Radicular pain

Acute pain

Acute pain is a sudden, sharp pain that lasts less than 3 months. Acute pain tends to be related to an injury or a temporary illness. It typically subsides after the injury heals or the illness subsides. Acute pain from an injury can evolve into chronic pain if the injury doesn’t heal properly or if the pain signals malfunction.

Chronic pain

Chronic pain is ongoing pain that lasts longer than 3 months. This pain is considered a disease state and affects 1 out of 5 adults. Chronic pain is difficult to diagnose and can be misdiagnosed. Chronic pain is caused by an underlying issue. Some of the conditions that produce chronic pain include headaches, arthritis, cancer, nerve pain, back pain, and fibromyalgia. Chronic pain is longer in duration and can be constant or intermittent. 

Neuropathic pain

Neuropathic pain results from damage to nerves or other parts of the nervous system. The pain is shooting, stabbing, or burning in nature. Sometimes it feels like pins and needles. It can affect sensitivity to touch and it makes individuals have difficulty feeling hot or cold sensations. Neuropathic pain is a common type of chronic pain. It can be intermittent and it can also be so severe that it makes performing daily tasks difficult.

Nociceptive pain

Nociceptive pain is a type of pain caused by damage to body tissue that is caused by injury. People often describe it as being a sharp, achy, or throbbing pain. This type of pain is often experienced in the muscles, joints, skin, tendons, and bones. Such pain can be both acute and chronic.

Radicular pain

Radicular pain is a very specific type of pain that occurs when the spinal nerve gets compressed or inflamed. The pain radiates along the distribution of the nerve or nerve root. It can radiate from the back to the lower limbs or from the neck to the upper limbs. Individuals with radicular pain can experience tingling, numbness, and muscle weakness. 

Pain scores 

The unidimensional pain intensity scales commonly used are:

Numeric Rating Scale (NRS), 

Visual Analog Scale (VAS),

Verbal Rating / Descriptor Scale (VRS/VDS).

The VAS is the most widely used tool for estimating both severity of pain and to judge the extent of pain. The patient is asked to select a point on a line drawn between two ends to express how intense he/she perceives pain. The VAS is a continuous scale comprised of a horizontal or vertical line, usually 100 mm long, anchored by two verbal descriptors i.e., “no pain” and “worst imaginable pain”-Fig 1.

Figure 1

Pain management

Pain management should be carried out using a multimodal approach. It should consist of treatments from one or more clinical disciplines that are incorporated

into an overall treatment plan. This allows for different approaches to address the pain problem. Multidisciplinary approaches address different aspects of pain including psychosocial effects on the patient [2,3,4]. Such a coordinated, integrated approach reduces pain severity, improves mood and overall quality of life, and improves function [5,6].

Opioid and nonopioid analgesics are the main drugs used to treat pain. Antiseizure, antidepressants and other central nervous system (CNS)–active drugs are also used for chronic or neuropathic pain and can be first-line therapy for some conditions. Nerve stimulation, neuraxial infusion, and neural blockade can help in some patients.

Cognitive-behavioral interventions can reduce pain and pain-related disability and help patients cope with the pain. These interventions include counseling the patient to develop personal coping strategies and counseling the patients and their families to work together to manage pain.

Nonopioid Analgesics

Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are effective for mild to moderate pain. Most of the NSAIDs are given orally. Ibuprofen, ketorolac, diclofenac, and acetaminophen can be given parenterally. The advantage of using nonopioids is that they do not cause physical dependence or tolerance.

Acetaminophen has no antiplatelet effects and no anti-inflammatory effects and does not cause gastric irritation.

Aspirin is the cheapest NSAID, but unfortunately, it has irreversible antiplatelet effects and it increases the risk of gastrointestinal (GI) bleeding.

NSAIDs have analgesic and anti-inflammatory effects as well as antiplatelet effects. They inhibit cyclooxygenase (COX) enzymes and hence reduce the production of prostaglandins. There are several classes of NSAIDs, which have different mechanisms and adverse effects (Fig 1):

Fig 1.

There are 2 types of COX inhibitors i.e nonselective COX inhibitors (eg, ibuprofen, naproxen) and selective COX-2 inhibitors (coxibs; eg, celecoxib)

Both the COX inhibitors are effective analgesics. The coxibs have the lowest risk of gastric ulceration and gastritis. 

COX-2 inhibition has a prothrombotic effect that can increase the risk of myocardial infarction, claudication, and stroke. This effect varies with the type of drug, as well as by the dose and duration of use. The risk is very low with some nonselective COX inhibitors such as ibuprofen, naproxen, and coxibs. All NSAIDs should be used cautiously in patients with clinically significant atherosclerosis or multiple cardiovascular risk factors because of the potential for prothrombotic effects of all NSAIDs.  The use of NSAIDs can be associated with renal insufficiency, hypertension, and cardiac-related events.

There are no significant side effects if NSAIDs are used for a short duration. Whenever therapy is likely to be long-term (eg, months) some clinicians use a coxib first because the risk of GI adverse effects is lower. Coxib is used in patients who are predisposed to GI adverse effects, such as older patients, patients taking steroids, and those with a history of peptic ulcer disease or gastritis. 

All NSAIDs should be used cautiously in patients with renal insufficiency. 

If a lower dose provides inadequate analgesia, a higher dose is given, up to the conventional safe maximum dose. If with higher dose analgesia remains inadequate, the drug should be stopped. During long-term NSAID therapy, it is prudent to monitor for occult blood in stool and changes in the blood count, electrolytes, and hepatic and renal function.

Acetaminophen can be effective for the treatment of mild to moderate pain. The use of acetaminophen can be associated with dose-dependent liver toxicity, especially if the drug is taken at high doses, with alcohol, or by those with liver disease [7].

Opioid Analgesics

Opioid is a term used for natural or synthetic substances that bind to specific opioid receptors in the central nervous system (CNS). Opioids are also called narcotics. Opioids have both sleep-inducing and analgesic effects.

Some opioids have both agonist and antagonist actions. The potential for abuse among individuals with a known history of abuse or addiction is lower with agonist-antagonists such as buprenorphine and butorphanol than with pure agonists such as morphine, oxycodone, and hydromorphone. Agonist-antagonist drugs have a ceiling effect for analgesia and they induce a withdrawal syndrome in individuals already physically dependent on opioids.

Opioid analgesics have proven efficacy in the treatment of pain. The risk of opioid misuse has to be kept in mind when using opioids for the treatment of pain. Underuse of opioids can result in needless pain and suffering. 

Some of the reasons for underusage leading to undertreatment include:

  • Underestimation of the effective dose
  • Overestimation of the risk of adverse effects

Simultaneous treatment of the condition causing the pain can limit the duration of severe pain and the need for opioids.

For acute pain, short-acting (immediate-release) pure agonist drugs are used at the lowest effective dosage and for a short time. The Centers for Disease Control and Prevention (CDC) guidelines recommend 3 to 7 days[8]. Using opioids at higher doses and for a longer time increases the risk of needing long-term opioid therapy, adverse effects, and misuse of opioids. Opioids should not be withheld when treating cancer pain. In such cases, adverse effects can be prevented or managed, and addiction is not much of a concern.

There is no good evidence to support the use of opioids for the long-term treatment of chronic pain due to non-terminal disorders. Long-term opioid therapy can result in adverse effects such as addiction, overdose, respiratory depression, and death. In patients with chronic pain due to non-terminal disorders, lower-risk nonopioid therapies should be tried before opioids.

If nonopioid therapy has been unsuccessful in patients with chronic pain due to non-terminal disorders, opioid therapy can be considered. In such cases, opioids are used in combination with nonopioid therapies. The goals, expectations, and risks of treatment should be explained to the patient. The patient should also be counseled about the misuse of the drug.

When treatment with opioids is appropriate the chronic pain can be treated with long-acting formulations. Long-acting formulations should be avoided in opioid-naive patients because of a higher risk of serious adverse effects. 

Patients on long-term (more than 3 months) opioid therapy are regularly assessed for pain control, functional improvement, adverse effects, and signs of misuse of the drug. 

Opioid therapy should be tapered and stopped if the following occur:

  • Patients continue to have persistent severe pain despite increasing opioid doses.
  • Patients do not adhere to the treatment protocol
  • Physical or mental function does not improve.

All patients treated with opioids for more than a few days develop physical dependence i.e they develop withdrawal symptoms when a drug is stopped. They also develop tolerance i.e they develop decreased response to the same dose of a drug that is used repeatedly. Therefore, opioids should be used for as short periods as possible. In patients who have developed dependence, the dose should gradually be tapered to control withdrawal symptoms when opioids are no longer needed. 

Different opioids have different potencies based on their ability to bind to opioid receptors. Knowing the interrelationship of these potencies is essential if patients need to be transitioned from one opioid to another or from an oral to an IV form. A 30 mg of oral morphine is equivalent to:

  • 10 mg of IV morphine (a 3:1 oral-to-IV ratio)
  • 7.5 mg of oral hydromorphone
  • 20 mg of oral oxycodone

Route of administration

In patients who are able to tolerate oral medications, oral opioids may be used for the treatment of acute pain. Especially in patients who need medications for a long time, the oral or transdermal route is preferred. Both these routes provide stable blood levels. 

Sublingual formulations of fentanyl are available. Lozenges can be used for sedation in children.

The intravenous (IV) route provides the most rapid onset but the duration of analgesia is short. Sometimes continuous IV infusion, with patient-controlled supplemental doses are used. This approach is used most often for postoperative pain control.

The intramuscular (IM) route provides analgesia for a longer duration than IV but the IM injections can be painful, and absorption can be erratic. 

Intraspinal opioids can provide relief, which is prolonged when a hydrophilic drug such as morphine is used. They are typically used perioperatively.


In opioid-naive patients, the initial dose is usually the lowest available starting dosage of the immediate-release formulation. It is increased incrementally by the smallest amount practical until analgesia is satisfactory or adverse effects set in.  Long-acting opioids are not used as first-line treatment in opioid-naive patients. Nonopioid analgesics are usually given concomitantly. 

Opioid-naive older patients typically require lower doses than younger patients because older patients are more sensitive to opioids and are predisposed to side effects. 

When opioids are given parentally the patient must be monitored for sedation and respiratory depression. Short-acting opioids are used initially. The doses of opioids for patients with chronic noncancer pain are typically decided case by case.

Patients in hospitals with severe pain and whose oral analgesics are inadequate can be given patient-controlled IV analgesia. The physician decides on the amount and interval of the bolus dose to be administered. A bolus dose of 1 mg morphine or 0.2 mg hydromorphone as often as every 6 minutes is provided when the patient presses a button. Only the patient is allowed to press the administration button. 

A baseline infusion of morphine, 0.5 to 1 mg/hour can be used. A baseline infusion should be used with caution, and it should only be used in patients who are alert enough to manage patient-controlled analgesia. Patients with prior opioid exposure or those with chronic pain require a higher bolus and baseline infusion dose. 

Patients who have dementia cannot use patient-controlled analgesia, nor can young children.

Treatment of chronic pain with opioids is only done when other options have been tried and found to be not effective. The effective opioid dose can remain constant for prolonged periods when used for long-term treatment of chronic pain. There will be some patients who need intermittent dose escalation when the pain gets more severe as in patients with progressive neoplasm. 

Methadone has the highest rate of opioid-induced deaths. It should only be prescribed by practitioners trained in its use. It should be started at a low dose and its use should be closely monitored. Methadone can prolong the cardiac QT interval hence the QTc interval should be assessed by ECG before methadone initiation. 

Adverse effects

The common adverse effects at the start of therapy with opioids include:

  • Sedation and mental clouding
  • Respiratory depression
  • Constipation
  • Nausea and vomiting
  • Itch
  • Myoclonus

Opioids tend to have more adverse effects such as constipation and sedation in older patients. The risk of falls is high in such patients. Opioids can cause urinary retention in men with prostatic hyperplasia.

In patients with the following disorders, opioids should be used cautiously:

  • COPD because of the risk of respiratory depression 
  • Hepatic disorders because drug metabolism is delayed
  • Untreated obstructive sleep apnea because of risk of respiratory depression 
  • Some neurologic disorders, such as dementia and encephalopathy, because of risk of delirium 
  • Severe renal insufficiency because metabolites can accumulate and cause problems

Sedation is a common side effect of opioids. Patients should avoid driving and make sure they do not fall. In patients in whom sedation impairs the quality of life, certain stimulant drugs may be given intermittently or regularly to some patients. 

Methylphenidate at a dose of 5 to 10 mg orally once or twice a day, titrated by 5 mg every 3 days to a maximum dose of 40 mg a day can be given to such patients. 

Dextroamphetamine at an initial dose of 2.5 mg orally once or twice a day can alternatively be used. Modafinil at an initial dose of 100 mg orally for 3 to 7 days, then 200 mg orally once a day is another alternative for these patients.

In some patients, caffeine-containing beverages provide enough stimulation. Stimulants can also potentiate analgesia.

The risk of overdose or respiratory depression is higher when patients are taking other sedatives, such as muscle relaxants, benzodiazepines, gabapentin, and alcohol. The risk is highest with benzodiazepines. Benzodiazepines should not be used with opioid therapy. The risk is also high when patients have comorbidities that affect hepatic or renal metabolism.

Risk factors for respiratory depression also include: 

  • History of renal disease, heart failure, stroke, or chronic pulmonary disease
  • Untreated or undertreated chronic obstructive pulmonary disease or obstructive sleep apnea
  • Psychiatric disorders
  • Substance use disorder
  • Concurrent use of psychoactive drugs
  • Use of long-acting opioids, high-dose opioids, or methadone

Hence, to reduce the risk for respiratory depression sleep apnea should be treated, patients should be advised not to drink alcohol, benzodiazepines should not be prescribed and long-acting opioids should be avoided.

Nausea can be treated with the following medications:

  • Hydroxyzine 25 to 50 mg orally every 6 hours
  • Ondansetron 4 mg orally or IV every 8 hours
  • Metoclopramide 10 to 20 mg orally every 6 hours
  • Prochlorperazine 10 mg orally or 25 mg rectally every 6 hours

Itching is caused by histamine release and can be treated with antihistamines. Diphenhydramine 25 to 50 mg orally or IV can be given to the patient. In hospitalized patients, nalbuphine 2.5 to 5 mg IV every 4 hours is more effective than diphenhydramine.

Constipation is common in patients who take opioids for more than a few days. It is more common in the elderly and immobile patients. Preventive treatment should be started with more fluids and more fiber intake. Laxatives such as senna and polyethylene glycol can be given daily. A drug that is specific for opioid-induced constipation can also be used. 

Effective drugs include:

  • Naloxegol 25 mg orally once a day 
  • Methylnaltrexone 12 mg/0.6mL subcutaneously or 450 mg orally once a day
  • Lubiprostone 24 mcg orally 2 times a day

Persistent constipation can be treated with oral magnesium citrate 240 ml daily, or oral lactulose 15 ml twice daily. Some patients will require regular enemas.

For urinary retention, double voiding or using the Credé method during voiding can help. Some patients benefit from an alpha-adrenergic blocker such as oral tamsulosin 0.4 mg daily.

Neuroendocrine effects are also possible. Typically reversible hypogonadism can be seen. Symptoms can include loss of libido, fatigue, infertility due to low levels of sex hormones, and, in women, amenorrhea. Low levels of androgens also lead to osteoporosis and hence patients taking long-term opioid therapy would require intermittent bone density testing.

Opioid misuse and abuse

Opioids are the leading cause of fatal drug overdose and accidental death in the US. The risk of fatal drug overdose increases significantly when opioids are used with benzodiazepines. 

The misuse of opioids may be intentional or unintentional. Abuse refers to recreational or nontherapeutic use of opioids for euphoria and other psychotropic effects. About one-third of the patients taking long-term opioids for chronic pain may misuse the prescribed opioids.

Addiction refers to compulsive use despite harm and negative consequences and it is typically marked by impaired control and craving. Discontinuation of the drug or a significant decrease in the dose can cause withdrawal symptoms. 

Rather than addiction, opioid use disorder is the preferred term. Opioid use disorder refers to a compulsive, long-term self-administration of opioids for nontherapeutic purposes that leads to significant distress or impairment. 

Opioid use disorder is diagnosed if  2 or more of the following are observed over a period of 12 months:

  • Taking opioids in larger amounts or for a longer time than is needed
  • Persistently desiring or unsuccessfully attempting to control or decrease opioid use
  • Spending a great deal of time trying to obtain or use opioids, or recover from opioid effects
  • Having a craving or strong desire to use opioids
  • Using opioids repeatedly resulting in failing to meet daily obligations at home, work, or school
  • Continuing to use opioids despite having persistent or recurrent social or interpersonal problems due to the opioid use
  • Giving up or reducing important work, social, or recreational activities because of opioid use
  • Having tolerance to opioids
  • Having opioid withdrawal symptoms
  • Continuing to use opioids in physically hazardous situations
  • Continuing to use opioids despite having a persistent or recurrent physical or psychologic disorder caused or worsened by opioids

Tolerance and withdrawal symptoms also occur in patients who take opioids under medical supervision. Such tolerance and withdrawal symptoms are not considered as opioid use disorders.

There are several risk factors for developing opioid use disorder and these include:

  • History of alcohol or drug abuse by the patient
  • History of alcohol or drug abuse in the family
  • Use of psychoactive drugs
  • Current or past major psychiatric disorder 
  • Younger age, usually less than 45 years

All patients who are treated with opioids should be monitored closely to make sure that the opioid therapy is used safely. Monitoring should include periodic unannounced urine drug tests to check for the presence of the prescribed drug and the absence of illicit drugs.

Current recommendations for urine drug screening include:

  • When a prescription is first given
  • At least once a year
  • More frequently if the risk is high or there is concern

Even when there are risk factors for developing an opioid use disorder, treatment can be continued. However, the clinicians should use more stringent measures to prevent abuse and addiction [9]. 

Some of these measures include:

  • Only small amounts are prescribed each visit and frequent visits are required for refills
  • Urine drug screening is carried out to monitor that the patient is adhering to treatment and to make sure that the patient is not diverting the drugs
  • So-called “lost” prescriptions are not refilled
  • Use of tamper-resistant opioid formulations to deter abuse by chewing or by crushing and injecting oral preparations
  • Buprenorphine formulations are useful for analgesia since they have a ceiling effect on the risk of sedation and respiratory depression

Problematic patients are usually referred to a pain specialist or a substance use specialist. 

When an opioid is first prescribed to a patient, the clinician should provide relevant information to the patient. If the patient develops opioid use disorder, the physician is responsible for offering and arranging evidence-based treatment. 

All patients have to be told about the risks of combining opioids with alcohol and anxiolytics. 

Opioid antagonists

Opioid antagonist is an opioid-like substance that binds to opioid receptors but produces little or no agonist activity. Opioid antagonists are used mainly to reverse symptoms of opioid overdose, especially respiratory depression. Some of these antagonists include:

1. Naloxone 

Naloxone acts in less than 1 minute when given intravenously and slightly less rapidly when given IM. It can also be administered sublingually or endotracheally. Its duration of action is about 60 to 120 minutes. Opioid-induced respiratory depression usually lasts longer than the duration of antagonism; hence, repeated doses of naloxone and close monitoring are necessary. 

The dose of naloxone for acute opioid overdosage is 0.4 mg IV every 2 to 3 minutes as needed and is titrated to adequate respiration. If repeated doses are required, the dose can be increased to a maximum of 2 mg IV per dose. 

In patients receiving long-term opioid therapy, naloxone should be used only to reverse respiratory depression and must be given cautiously to avoid producing withdrawal symptoms or recurrent pain.

Naloxone is also available as an auto-injector (IM) and a nasal spray. A single spray of 2 or 4 mg in 0.1 mL is sprayed into one nostril. For the auto-injector, the dose is 2 mg injected IM or subcutaneously into the thigh. 

2. Nalmefene is similar to naloxone. Its duration of action is about 4 to 8 hours. Nalmefene is sometimes used to ensure prolonged opioid reversal.

3. Naltrexone is an oral opioid antagonist. It is given as adjunctive therapy in opioid and alcohol addiction. It is long-acting and is generally well-tolerated.

Adjuvant Analgesic Drugs

There are other drugs that are used as analgesics. These include antiseizure drugs such as gabapentin, pregabalin, antidepressants like tricyclics, duloxetine, venlafaxine, bupropion, and many others. These drugs are most notably used for neuropathic pain.

Gabapentin is widely used for headache syndromes and neuropathic pain. Pregabalin is very similar to gabapentin but it has more stable pharmacokinetics. Dosing 2 times a day is as efficacious as dosing 3 times a day and it results in better compliance. Pregabalin is effective for neuropathic pain and fibromyalgia. There is some evidence that suggests it is effective as an anxiolytic as well.

The primary mechanism of action of tricyclic antidepressants, such as amitriptyline, nortriptyline, and desipramine, is blocking the reuptake of serotonin and norepinephrine. These drugs are effective for neuropathic pain, visceral pain syndromes, myofascial pain syndromes, some central neuropathic pain syndromes, and headache syndromes.

Duloxetine is also a serotonin and norepinephrine reuptake inhibitor. It is effective for diabetic neuropathic pain, chronic musculoskeletal pain (including low back pain), fibromyalgia, and chemotherapy-induced neuropathy. The effects and mechanism of action of Venlafaxine are similar to those of duloxetine.

Topical drugs such as capsaicin cream, topical NSAIDs, other compounded creams, and lidocaine 5% patch have little risk of adverse effects and are also used for pain. 

Neural Blockade

Short-term and sometimes long-term pain relief can be obtained by interrupting nerve transmission in peripheral or central pain pathways with drugs or via physical methods. 

Neuroablation or pathway ablation is rarely used. It is usually reserved for patients who have an advanced disorder and a short life expectancy.

Local anesthetic drugs for pain relief such as lidocaine can be given IV, subcutaneously, intrathecally, intrapleurally, transdermally, or even epidurally. Epidural analgesia using local anesthetics or opioids is often used for postoperative pain. In patients with localized pain and a short life expectancy, long-term epidural drug administration is occasionally used. An implanted pump is often used for long-term neuraxial infusion, via the intrathecal route. 

In neuroablation, the nociceptive pathways are interrupted surgically or by using radiofrequency or microwave energy, cryoablation, or caustic substances such as phenol or high-concentration alcohol. Neuroablation is usually more effective for somatic pain than for visceral pain.

Neuroablation procedures are commonly used to treat axial spinal pain. These procedures involve radiofrequency ablation of the medial branches of the dorsal spinal root rami that innervate the facet joints or ablation of the lateral branches that innervate the sacroiliac joint. Neroablation of the genicular nerve is also carried out for refractory knee pain. Neroablation of the articular sensory branches of the obturator and femoral nerves has also been carried out for hip pain. For shoulder pain, neuroablation of the articular sensory branches of the suprascapular, axillary, and lateral pectoral nerves can be carried out.


Stimulation of neural tissues can reduce pain by activating endogenous pain pathways. Certain types of neuropathic pain such as that after failed back surgery,  and in patients with complex regional pain syndrome can be treated using an electrode placed epidurally to stimulate the spinal cord.

Transcutaneous electrical nerve stimulation (TENS) is also used to treat pain. It uses a low current at a low frequency to help treat pain. Studies of its efficacy are, however, lacking in number and design, with high risks of bias commonly reported [10]. An evaluation of 49 systematic reviews, randomized controlled trials (RCTs), and observational studies found that there is insufficient evidence to assess the effectiveness of TENS for acute low-back pain [11].

There are individual studies that have investigated the effectiveness of TENS for postpartum pain, phantom limb pain, and knee osteoarthritis [12].

Despite the fact that there is limited evidence of efficacy, partially stemming from a lack of large RCTs, TENS is considered a safe self-care option for patients with appropriate education.

Some of the advances in neuromodulation techniques and technologies include:

  • High-frequency stimulation
  • Burst spinal cord stimulation waveforms
  • Dorsal root ganglion stimulation
  • Small flexible peripheral nerve stimulators
  • Improved MRI compatibility, which has greatly expanded the clinical situations in which neuromodulation can be used

High-frequency stimulation is effective in patients with neuropathic limb pain. 

A more focused neuromodulation treatment is dorsal root ganglion stimulation. It treats localized neuropathic pain within limited dermatomes.

Peripheral nerve stimulation is frequently used to treat intractable neuropathic pain when a single peripheral nerve is involved. Some examples include post herniorrhaphy pain syndrome, headache syndromes such as occipital neuralgia, and meralgia paresthetica. It is also used to stimulate branches of the axillary nerve to treat hemiplegic shoulder pain after a stroke. Peripheral nerve stimulation can be useful in treating postoperative pain during the first several weeks after total knee replacement, anterior cruciate ligament surgery, and foot surgery.

Peripheral nerve stimulation involves the percutaneous insertion of a small, thin, flexible electrode leads next to the affected nerve. The leads are then connected to a stimulator, which is fixed to the skin adjacent to the leads. 

Massage therapy 

Massage therapy can be effective in reducing pain. There are several types of massage therapy, including shiatsu, Swedish, and deep tissue (myofascial release).

In Swedish massage, the therapist uses long strokes, deep circular movements, and kneading. Shiatsu massagers use their fingers, thumbs, and palm to apply pressure. Deep tissue massagers focus on myofascial trigger points, with attention on the deeper layers of tissues.


Traction is also a technique used to treat spinal pain. A review of the evidence, however, has failed to demonstrate the clinical effectiveness of traction as an effective, evidence-based best practice. The field in general lacks high-quality RCTs that examine the effectiveness of traction as an isolated treatment modality for low-back [13] or neck pain [14].

Cold and Heat 

Cold and heat have been used in the treatment of a variety of acute and chronic pain conditions. The use of cold compress has long been a component of the RICE  i.e rest, ice, compression, elevation, paradigm for the treatment of acute pain.

The effects and duration of this therapy are mitigated by the initial cause of the pain. Cold therapy, for instance, has been shown to decrease the pain of hip arthroplasty on the second day but not the first or third day after surgery and did not decrease blood loss from the surgery [15].

There is significant evidence for the efficacy and safety of heat wraps in specific conditions, most notably for acute low back pain. A review of nonpharmacologic therapies found that superficial heat had good evidence of efficacy for the treatment of acute low-back pain [16]. There is another review that found moderate evidence for heat wraps for both symptom and functional improvements [17].

Therapeutic ultrasound (TU)

Therapeutic ultrasound is believed to deliver heat to deep tissues for improved injury healing. A 2001 review by Robertson and Baker concluded that there was little evidence that TU is more effective than placebo for pain treatment in a range of musculoskeletal conditions [18].

More recent reviews of specific pain syndromes that are available from the Cochrane Database of Systematic Reviews reveal similar findings [19,20]. 


Bracing has been discouraged in pain management because of fears of deconditioning and muscle atrophy. There is, however, some evidence that bracing (non-rigid brace) for at least short periods of time, may improve function and does not result in muscle dysfunction [21].

Behavioral Health Approaches

In recent decades, Pain management experts, in recent decades have recognized the important relationship between psychological health and pain [22,23,24]. Psychological factors play an important role in an individual’s experience and response to pain [25]. Psychological factors can affect treatment adherence, pain chronicity, and disability status [26].

Undiagnosed and untreated psychological concerns in individuals with pain are associated with decreased treatment adherence and increased disability [27].

Patients with chronic pain are also at increased risk for psychological distress. 

Psychological interventions can play an important role in reducing disability in these patients. Behavioral health approaches should be considered a key component of multidisciplinary pain management. 

Behavioral therapy (BT) 

Behavioral therapy for pain focuses largely on identifying and reducing maladaptive pain behaviors and increasing adaptive behaviors. This is achieved by minimizing reinforcement of maladaptive behaviors and providing reinforcement of well behaviors. Avoidance behaviors are reduced through gradual exposure to fear-provoking stimuli such as exercises. 

The main aim of BT in the treatment of pain is to improve function. Treatment with BT has been effective in reducing pain behaviors and distress and improving overall function. It can be more cost-effective than active physical treatment [28].

Cognitive behavioral therapy (CBT) 

The aim of cognitive behavioral therapy is to reduce maladaptive behavior and improve overall function. Besides focusing on altering behavioral responses to pain, CBT also focuses on shifting cognitions and improving pain-coping skills [29].

Psychoeducation about the relationship between psychological factors such as thoughts, and feelings, and pain is carried out. Restructuring of maladaptive thought patterns and training in a variety of pain coping strategies is done. CBT   can help improve self-efficacy, pain catastrophizing, and overall functioning [30,31].

CBT has been found to produce long-term improvements in patients with low-back pain and fibromyalgia [32].

Acceptance and commitment therapy (ACT)

Acceptance and commitment therapy is a form of CBT that teaches individuals to observe and accept thoughts and feelings, live in the present moment, and behave in a manner that serves an individual’s chosen values. ACT focuses on creating psychological flexibility through acceptance of psychological and physical experiences rather than by challenging them [33,34].

Mindfulness-based stress reduction (MBSR) 

Mindfulness-based stress reduction is a mind-body treatment that is usually delivered in a group and it focuses on improving patients’ awareness and acceptance of their physical and psychological experiences through intensive training in mindfulness meditation [35].

Mindfulness meditation teaches individuals to self-regulate their pain and pain-related comorbidities by developing awareness and acceptance of present moment sensations, thoughts, and emotions [36,37].

MBSR is an effective intervention for helping individuals cope with a variety of pain conditions such as including low back pain, rheumatoid arthritis, and multiple sclerosis [38,39].

MBSR also has a definitely good impact on pain intensity sleep quality, fatigue, and overall physical functioning and well-being [40,41,42].

Emotional awareness and expression therapy (EAET)

Emotional awareness and expression therapy is an emotion-focused therapy for patients who suffer from centralized pain conditions following trauma. Here the patients are taught that their pain is exacerbated or maintained by unresolved emotional experiences that influence neural pathways involved in pain. The patients are taught to become aware of these unresolved experiences, that include suppressed or avoided trauma, conflict, and adversity. They are advised to express their emotions related to these experiences. Patients are able to learn that control over pain can be achieved through emotional awareness and expression.

Patients are encouraged to approach an experience rather than inhibit or avoid important emotions and interpersonal interactions. Research shows that EAET has a positive impact on pain intensity, pain interference, and depressive symptoms [43].

Self-regulatory or psychophysiological approaches

Self-regulatory or psychophysiological approaches include treatments such as hypnotherapy, biofeedback, and relaxation training. The mind-body connection is used to help patients with pain develop control over their physiologic and psychological responses to pain [23]. Biofeedback involves monitoring and providing real-time feedback about physiologic functions associated with the pain experience, such as heart rate, muscle tension, and skin conductance. The overall goal of biofeedback is to improve awareness and voluntary control over bodily reactions that are associated with pain exacerbations [44].

Biofeedback training has been effective for chronic headaches and migraine in children and adults [45]. Hypnotherapy and relaxation training involve altering attentional processes and heightening the experience of physical and psychological relaxation.

Relaxation training is often used in conjunction with biofeedback to enhance relaxation skills and increase physiological awareness [23]. Hypnotherapy is also used to manage cancer pain, arthritis, low-back pain, fibromyalgia, pain from SCD,  temporomandibular joint pain, and other pain conditions [46]. As with relaxation training, hypnotherapy induces an altered state of consciousness guided by a hypnotherapist that focuses the individual’s attention to alter her or his experience of pain.

Access to Psychological Interventions

Many patients with pain receive inadequate care despite widespread understanding of the importance of psychological interventions in the management of pain [47,48].

There are several factors that contribute to this problem. These include 

  • Clinical barriers such as treatment accessibility, knowledge gaps, provider attitudes
  • Health care system-related barriers such as cost and reimbursement issues
  • Patient-related barriers such as stigma, and attitudinal variables 

When access to providers and costs are limiting factors, low-cost and scalable approaches delivered through telehealth and internet technologies can provide a low-burden, effective alternative to traditional treatment approaches [49].

Brief telehealth and digitally delivered treatments allow broad patient access and yield outcomes that are similar to traditional in-person psychological interventions for chronic pain [50].

The patients and providers need to know about psychological treatments. Health professionals must have a sufficient understanding of the biopsychosocial model of Pain. They have to know how to appropriately assess and refer patients for behavioral treatment [51,52]. This can be achieved by improving training and education in pain management [53,54] and enhancing public awareness of the biopsychosocial aspects of pain [55].


  1. Raja SN, Carr DB, Cohen M, et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 2020;161(9):1976-1982. doi:10.1097/j.pain.0000000000001939
  2. Gatchel RJ, McGeary DD, McGeary CA, Lippe B. Interdisciplinary chronic pain management: past, present, and future. Am Psychol. 2014;69(2): 119-130. doi:10.1037/a0035514
  3. Gatchel RJ, Peng YB, Peters ML, Fuchs PN, Turk DC. The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull. 2007;133(4):581-624. doi:10.1037/0033- 2909.133.4.581.
  4. Staats PS, Hekmat H, Staats AW. The psychological behaviorism theory of pain: A basis for unity. Pain Forum. 1996;5(3):194-207. doi:10.1016/S1082- 3174(96)80031-6.
  5. Gatchel RJ, Okifuji A. Evidence-based scientific data documenting the treatment and cost-effectiveness of comprehensive pain programs for chronic nonmalignant pain. J Pain Off J Am Pain Soc. 2006;7(11):779-793. doi:10.1016/j.jpain.2006.08.005
  6. Oslund S, Robinson RC, Clark TC, et al. Long-term effectiveness of a comprehensive pain management program: strengthening the case for interdisciplinary care. Proc Bayl Univ Med Cent. 2009;22(3):211-214.
  7. Major JM, Zhou EH, Wong H-L, et al. Trends in rates of acetaminophen-related adverse events in the United States. Pharmacoepidemiol Drug Saf. 2016;25(5):590-598. doi:10.1002/pds.3906
  8. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016. JAMA. 2016;315(15):1624-1645. doi:10.1001/jama.2016.1464.
  9. Babu KM, Brent J, Juurlink DN: Prevention of opioid overdose. N Eng J Med 380:2246–2255, 2019. doi: 10.1056/NEJMra1807054. 
  10. Vance CG, Rakel BA, Dailey DL, Sluka KA. Skin impedance is not a factor in transcutaneous electrical nerve stimulation effectiveness. J Pain Res. 2015;8:571-580. 
  11.  McIntosh G, Hall H. Low back pain (acute). BMJ Clin Evid. 2011;2011.            https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217769/.
  12.  Pain Management Best Practices Inter-Agency Task Force Report (DRAFT FINAL REPORT 5/6/2019) at https://www.hhs.gov/sites/default/files/pain-mgmt-best-practices-draft-final-report-05062019.pdf.
  13.  Clarke J, van Tulder M, Blomberg S, de Vet H, van der Heijden G, Bronfort G. Traction for low back pain with or without sciatica: an updated systematic review within the framework of the Cochrane collaboration. Spine. 2006;31(14):1591-1599.
  14.  Graham N, Gross A, Goldsmith CH, et al. Mechanical traction for neck pain with or without radiculopathy. Cochrane Database Syst Rev. 2008; (3): CD006408.
  15.  Ni S-H, Jiang W-T, Guo L, et al. Cryotherapy on postoperative rehabilitation of joint arthroplasty. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2015;23(11):3354-3361. doi:10.1007/s00167-014-3135-x.
  16.  Chou R, Huffman LH, American Pain Society, American College of Physicians. Nonpharmacologic therapies for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med. 2007;147(7):492-504.
  17.  McIntosh G, Hall H. Low back pain (acute). BMJ Clin Evid. 2011;2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217769/.
  18.  Robertson VJ, Baker KG. A review of therapeutic ultrasound: effectiveness studies. Phys Ther. 2001;81(7):1339-1350.
  19.  Ebadi S, Henschke N, Nakhostin Ansari N, Fallah E, van Tulder MW. Therapeutic ultrasound for chronic low-back pain. Cochrane Database Syst Rev. 2014;(3):CD009169.
  20.  Rutjes AW, Nüesch E, Sterchi R, Jüni P. Therapeutic ultrasound for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2010;(1):CD003132.
  21.  Azadinia F, Ebrahimi E Takamjani, Kamyab M, Parnianpour M, Cholewicki J, Maroufi N. Can lumbosacral orthoses cause trunk muscle weakness? A systematic review of literature. Spine J. 2017 Apr;17(4):589-602. doi: 10.1016/j.spinee.2016.12.005. Epub 2016 Dec 14. PMID: 27988341.
  22.  Gatchel RJ, Peng YB, Peters ML, Fuchs PN, Turk DC. The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull. 2007;133(4):581-624.
  23.  Kerns RD, Sellinger J, Goodin BR. Psychological treatment of chronic pain. Annu Rev Clin Psychol. 2011;7:411-434. doi:10.1146/annurev-clinpsy 090310-120430
  24.  Manchikanti L, Fellows B, Singh V. Understanding psychological aspects of chronic pain in interventional pain management. Pain Physician. 2002;5(1):57-82.
  25. Chou R, Qaseem A, Snow V, et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of physicians and the American Pain Society. Ann Intern Med. 2007;147(7): 478-491.
  26.  Kligler B, Bair MJ, Banerjea R, et al. Clinical Policy Recommendations from the VHA State-of-the-Art Conference on Non-Pharmacological Approaches to Chronic Musculoskeletal Pain. J Gen Intern Med. 2018; 33(Suppl 1):16-23. doi:10.1007/s11606-018-4323-z.
  27.  Kellezi B, Coupland C, Morriss R, et al. The impact of psychological factors on recovery from injury: a multicentre cohort study. Soc Psychiatry Psychiatr Epidemiol. 2017;52(7):855-866. doi:10.1007/s00127-016-1299-z.
  28.  McCracken LM, Turk DC. Behavioral and cognitivebehavioral treatment for chronic pain: outcome, predictors of outcome, and treatment process. Spine. 2002;27(22):2564-2573.
  29.  Kaiser RS, Mooreville M, Kannan K. Psychological Interventions for the Management of Chronic Pain: a Review of Current Evidence. Curr Pain Headache Rep. 2015;19(9):43.
  30.  Jensen MP, Turner JA, Romano JM. Changes in beliefs, catastrophizing, and coping are associated with improvement in multidisciplinary pain treatment. J Consult Clin Psychol. 2001;69(4):655-662.
  31. Turner J, Jensen M, Romano J. Do beliefs, coping, and catastrophizing independently predict functioning in patients with chronic pain? Pain. 2000;85(1-2):115-125.
  32.  Skelly AC, Chou R, Dettori JR, et al. Noninvasive Nonpharmacological Treatment for Chronic Pain: A Systematic Review. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018. http://www.ncbi.nlm.nih.gov/books/NBK519953/.
  33.  McCracken LM, Vowles K. Acceptance and Commitment Therapy and Mindfulness for Chronic Pain: Model, Process, and Progress. Am Psychol. 2014.
  34. Vowles KE, McCracken LM. Acceptance and valuesbased action in chronic pain: a study of treatment effectiveness and process. J Consult Clin Psychol. 2008;76(3):397-407. doi:10.1037/0022-006X.76.3.397.
  35.  Cherkin DC, Sherman KJ, Balderson BH, et al. Effect of Mindfulness-Based Stress Reduction vs Cognitive Behavioral Therapy or Usual Care on Back Pain and Functional Limitations in Adults With Chronic Low Back Pain: A Randomized Clinical Trial. JAMA. 2016; 315(12): 1240-1249.
  36.  Zeidan F, Vago DR. Mindfulness meditation-based pain relief: a mechanistic account. Ann N Y Acad Sci. 2016;1373(1):114-127. doi:10.1111/nyas.13153.
  37.  Hilton L, Hempel S, Ewing BA, et al. Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis. Ann Behav Med Publ Soc Behav Med. 2017;51(2):199-213.
  38.  Pradhan EK, Baumgarten M, Langenberg P, et al. Effect of Mindfulness-Based Stress Reduction in rheumatoid arthritis patients. Arthritis Rheum. 2007;57(7):1134-1142. doi:10.1002/art.23010
  39.  Anheyer D, Haller H, Barth J, Lauche R, Dobos G, Cramer H. Mindfulness-Based Stress Reduction for Treating Low Back Pain: A Systematic Review and Meta-analysis. Ann Intern Med. 2017;166(11): 799-807. doi:10.7326/M16-1997.
  40.  Carlson LE, Garland SN. Impact of mindfulness-based stress reduction (MBSR) on sleep, mood, stress and fatigue symptoms in cancer outpatients. Int J Behav Med. 2005;12(4):278-285. doi:10.1207/s15327558ijbm1204_9.
  41.  Grossman P, Niemann L, Schmidt S, Walach H. Mindfulness-based stress reduction and health benefits. A meta-analysis. J Psychosom Res. 2004;57(1):35-43. doi:10.1016/S0022-3999(03)00573-7
  42.  Omidi A, Zargar F. Effects of mindfulness-based stress reduction on perceived stress and psychological health in patients with tension headache. J Res Med Sci Off J Isfahan Univ Med Sci. 2015;20(11):1058-1063. 
  43.  Burger AJ, Lumley MA, Carty JN, et al. The effects of a novel psychological attribution and emotional awareness and expression therapy for chronic musculoskeletal pain: A preliminary, uncontrolled trial. J Psychosom Res. 2016;81:1-8.
  44.  Neblett R. Surface Electromyographic (SEMG) Biofeedback for Chronic Low Back Pain. Healthcare. 2016;4(2).
  45.  Nestoriuc Y, Martin A, Rief W, Andrasik F. Biofeedback treatment for headache disorders: a comprehensive efficacy review. Appl Psychophysiol Biofeedback. 2008;33(3):125-140.
  46.  Elkins G, Jensen MP, Patterson DR. Hypnotherapy for the management of chronic pain. Int J Clin Exp Hypn. 2007;55(3):275-287.
  47.  Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. J Addict Med. 2015;9(5):358-367.  Heyward J, Jones C, Compton W. Coverage of
  48.  Nonpharmacologic Treatments for Low Back Pain Among US Public and Private Insurers. JAMA Netw Open. 2018;1(6). https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2705853.
  49.  Kerns RD, Krebs EE, Atkins D. Making Integrated Multimodal Pain Care a Reality: A Path Forward. J Gen Intern Med. 2018;33(Suppl 1):1-3. doi:10.1007/s11606-018-4361-6.
  50.  Heapy AA, Higgins DM, Goulet JL, et al. Interactive Voice Response–Based Self-management for Chronic Back Pain. JAMA Intern Med. 2017;177(6):765-773. doi:10.1001/jamainternmed.2017.0223.
  51.  Roditi D, Robinson ME. The role of psychological interventions in the management of patients with chronic pain. Psychol Res Behav Manag. 2011;4:41-49. doi:10.2147/PRBM.S15375.
  52.  Wahass SH. The Role of Psychologists in Health Care Delivery. J Fam Community Med. 2005;12(2):63-70.
  53.  Darnall BD, Scheman J, Davin S, et al. Pain Psychology: A Global Needs Assessment and National Call to Action. Pain Med Malden Mass. 2016;17(2):250-263. doi:10.1093/pm/pnv095.
  54.  Wandner LD, Prasad R, Ramezani A, Malcore SA, Kerns RD. Core competencies for the emerging specialty of pain psychology. Am Psychol. August 2018. doi:10.1037/amp0000330.
  55.  Becker WC, DeBar LL, Heapy AA, et al. A Research Agenda for Advancing Non-pharmacological Management of Chronic Musculoskeletal Pain: Findings from a VHA State-of-the-art Conference. J Gen Intern Med. 2018;33(Suppl 1):11-15. doi:10.1007/s11606-018-4345-6.

Wednesday, 25 May 2022

      Treatment of persistent shoulder pain

                              Dr. KS Dhillon

Persistent shoulder pain is a common clinical problem and it is often associated with limited range of motion and decreased function [1,2]. An estimated 20 percent of the population will suffer shoulder pain during their lifetime [3]. Shoulder pain is second only to low back pain in patients seeking care for musculoskeletal ailments. There are several causes of such persistent pain and these include glenohumeral osteoarthritis, rotator cuff tears, subacromial impingement, tendinitis, adhesive capsulitis, and subacromial bursitis [4].

Damage or dysfunction affecting one component of the shoulder can lead to secondary pathological changes, in other areas of the shoulder leading to persistent pain [4,5]. A rotator cuff tear, for example, can lead to mechanical and degenerative changes in the glenohumeral joint and that can result in symptomatology [4,6,7].

Effective treatment depends on an accurate diagnosis of the cause of the shoulder pain. The causes of the shoulder pain can include the following diagnosis, rotator cuff disorders, adhesive capsulitis, acromioclavicular osteoarthritis, glenohumeral osteoarthritis, and shoulder instability.

The initial treatment involves activity modification and analgesic medications. If no improvement occurs or if the initial presentation is very severe, a trial of physical therapy that focuses on the particular diagnosis is indicated. 

Combined local anesthetic and steroid injections can be used alone or in combination with physical therapy. The site of the injection depends on the diagnosis and it can be into the shoulder joint, subacromial space, or into the acromioclavicular joint. Injections into the glenohumeral joint are usually done under fluoroscopic guidance. 

Treatment Overview

A systematic review of randomised controlled trials of interventions for painful shoulder showed little evidence for or against the most common treatments of chronic shoulder disorders [8]. This is mainly because of a lack of well-designed clinical trials. Nevertheless, most patients with chronic shoulder disorders can initially be treated conservatively with a combination of activity modification, physical therapy, medications, and steroid injections if necessary.

The outcome of this approach is satisfactory in majority of the patients [9,10].  

Activity Modification

A simple treatment for reducing shoulder pain is activity modification.  Recommendations are based on the underlying diagnosis. Avoidance or reduction of overhead activity is the mainstay of treatment for patients with glenohumeral osteoarthritis, rotator cuff pathology, and adhesive capsulitis because this avoids the painful arc between 60 to 120 degrees. Heavy loading of the shoulder should be avoided in patients with glenohumeral osteoarthritis to reduce pain. Certain activities such as bench pressing, kayaking, and overhead throwing should be avoided in patients with an unstable shoulder. In patients with acromioclavicular osteoarthritis cross-body shoulder adduction, such as the motion performed in the golf swing or weight lifting, should be limited to prevent pain. 


Pain control with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or short-term opiate medication is imperative to allow for the progression of treatment. Although NSAIDs are widely used to treat pain, there is no conclusive evidence to support the use of NSAIDs over simple analgesia in the treatment of chronic shoulder pain [11]. The risks and benefits of each class of drugs should be considered before its use [4].

Physical Therapy

Physical therapy includes several types of treatment. There are several modalities to alleviate pain such as heat and ice, ultrasound, hyperthermia, and iontophoresis. Stretching and strengthening exercises improves overall shoulder function and relieves pain. 

The type of physical therapy will depend on the underlying etiology. Little evidence exists for the use of these therapeutic modalities alone [12]. A Cochrane review showed that strengthening and stretching exercises provide improved short-term recovery and long-term function in patients with rotator cuff disease [12].

Calis et al [13] carried out a study to compare the efficacy of sodium hyaluronate injection with the most common treatment methods, such as intraarticular steroid injection, and physical therapy modalities in patients with adhesive capsulitis. They found that physical therapy provided the best results as compared to other treatment modalities.

For success of physical therapy, the underlying diagnosis must be known and the patient must actively participate in the rehabilitation process on a daily basis.


Corticosteroid injections combined with a local anesthetic are administered if patients have a poor response to initial treatment for chronic shoulder disorders. The injection has to be directed toward the area of underlying pathology, such as the subacromial space, glenohumeral joint, or acromioclavicular joint. 

The role of subacromial injection for rotator cuff disease is an area of controversy as well as active research. There are two systematic reviews that found little evidence to support or refute the use of subacromial injections and there are two systematic reviews that found it to be beneficial for rotator cuff tendinitis and shoulder pain. There is another review that suggested a possible small benefit [14-18]. 

There are several studies that have found subacromial injections to be beneficial,  for short-term decrease in pain and increase in function [17,18,19,20].

A study by Koh KH [21] to assess the efficacy and safety of corticosteroid injections for adhesive capsulitis showed that corticosteroid injection is superior to placebo and physiotherapy in the short-term (up to 12 weeks), but there is no difference in outcomes between corticosteroid injection and oral nonsteroidal anti-inflammatory drugs at 24 weeks.

A systematic review of corticosteroid injections into the shoulder for adhesive capsulitis by Shah N [22] provided convincing evidence based on 3 high-quality studies in which use of multiple corticosteroid injections had beneficial effect on pain reduction, improved function and increased range of movements.

According to the American Academy of Orthopedic Surgeons (AAOS), there is moderate evidence to support the use of a single injection of steroids with local anesthetic for short-term pain relief and improvement in shoulder function in patients with rotator cuff tears [23].

In patients with adhesive capsulitis, intra-articular injections of steroids decrease pain and increase function, particularly in combination with physical therapy for stretching [18,24].

The AAOS does not recommend the use of intra-articular steroid injections for glenohumeral osteoarthritis [25]. The AAOS has no recommendation for use of hyaluronic acid injection in patients with glenohumeral osteoarthritis [4]. 

The AAOS endorses the use of steroid injection into the acromioclavicular joint for osteoarthritis despite few studies demonstrating its effectiveness [25]. 


Most patients respond to conservative treatment for shoulder pain. Those patients who do not respond to conservative treatment, surgical treatment may be required. Patients with continued instability or disabling pain that is not responsive to conservative treatment may require surgical treatment [4,25,26]. 

Treatment of Specific Conditions

1. Acromioclavicular osteoarthritis

Acromioclavicular osteoarthritis is a common condition and it can produce chronic shoulder pain. It can be associated with subacromial impingement syndrome of the shoulder. The mainstay of treatment is pain control and activity modification [25]. Pain control may be obtained with the use of NSAIDs or other analgesics. If there is a failure to obtain pain relief with analgesics, corticosteroid injections can be used. Corticosteroids are usually effective in short-term pain control for more severe cases [27]. Failure to improve or maintain function with conservative treatment may warrant surgical treatment. Resection of the distal clavicle is often effective in relieving the pain symptoms [28,29]. 

2. Adhesive capsulitis

The treatment of adhesive capsulitis can be challenging. Long-term follow-up studies show that adhesive capsulitis resolves spontaneously over one to two years without intervention [25,30]. The aim of treatment is to decrease the duration of symptoms. The treatment essentially involves activity modification to decrease pain, anti-inflammatory or analgesic medications, and a physical therapy regimen for stretching and mobilizing the shoulder, both with the therapist and at home.

In the event of no progress or slow progress after six weeks, an intra-articular steroid injection can be given. An intra-articular injection of corticosteroid has shown short-term benefits in reducing pain and disability at the six-week follow-up [31]. The accuracy of injection is improved with the use of a fluoroscope. If a dye is injected it can confirm the position of the needle. The dye will also provide an arthrogram, that can rule out other concomitant pathologies such as a rotator cuff tear. The need for surgical intervention is rare. Arthroscopic capsular release is usually not necessary. A manipulation of the shoulder under anesthesia may sometimes be required.

3. Rotator cuff disorders

Shoulder pain due to rotator cuff pathology can usually be treated successfully with conservative modalities [32,33]. The conservative treatment involves activity modification, physical therapy, and the use of anti-inflammatory or analgesic medications. The aim of physical therapy is to improve the strength, range of motion, and proprioception of the shoulder. If there is no improvement after several weeks, a subacromial corticosteroid injection may provide significant pain control that will allow range of motion to improve with physical therapy [34]. 

If the clinical assessment demonstrates that the rotator cuff is intact, a three to six-month trial of conservative treatment is usually adequate. For small rotator cuff tears also, a six to 12 weeks of nonoperative treatment is reasonable. Large retracted rotator cuff tears, sometimes seen in patients with a history of trauma or dislocation often need surgical intervention. These patients usually present with severe pain and significant supraspinatus, infraspinatus, and subscapularis weakness. Surgical treatment can be open, mini-open, or arthroscopic decompression and rotator cuff repair.

4. Glenohumeral osteoarthritis

Glenohumeral osteoarthritis is not a common condition and is a less common source of chronic shoulder pain. Glenohumeral osteoarthritis can produce significant pain and disability. The aim of treatment is to maintain overall function with adequate pain control. Pain control is obtained with anti-inflammatory or analgesic medications. If pain, however, is not adequately controlled, an intra-articular steroid injection may be given. There is, however, little evidence to support the use of steroid injection, and its use is not endorsed by the AAOS [25].

Physical therapy can help maintain shoulder function. Patients with shoulder osteoarthritis often have joint incongruity and aggressive attempts at increasing the range of motion can be counterproductive. The aim should be to maintain a functional, pain-free range of motion of the shoulder. 

In patients with advanced osteoarthritis who have severe disability, surgery may be required. Capsular release and arthroscopic debridement, hemiarthroplasty, and total shoulder arthroplasty are surgical options available [35]. There are, however,  no clinical trials or systematic reviews comparing conservative versus surgical treatment outcomes.

5. Glenohumeral joint instability

Glenohumeral instability leading to chronic shoulder pain may be related to an old dislocation of the shoulder or repetitive overuse in a young athlete with some ligamentous laxity. The initial treatment should focus on activity modification and an aggressive muscle strengthening program. Strengthening of the rotator cuff muscle and scapular stabilizer muscles can be very useful, particularly for athletes with traumatic instability of the shoulder [36]. Surgery has to be carried out if there is a failure to improve with conservative treatment or there is recurrent dislocation or subluxation. 

Sodium hyaluronate for treatment of shoulder pain

The role of hyaluronate (HA) treatment for chronic painful shoulder has not yet been elucidated although HA injections are commonly used. There is little evidence to support their use. None of the published studies have proven undeniable efficacy of HA for the treatment of chronic shoulder pain.

Saito et al [37] carried out a meta-analysis of randomized controlled trials that compared the efficacy of HA injections with that of placebo. The authors concluded that the meta-analysis provided evidence that HA injections are a valuable alternative to other conservative methods for treatment of chronic shoulder pain. The authors admitted that there were limitations of this meta-analysis. They said that only a few conclusions could be drawn from the meta-analysis because of the relatively small number of studies included. They empahasized the need of additional investigations on the use of HA injections for shoulder pain.

Furthermore, in the article by Saito et al, the term periarthrities was used and a precise diagnosis was not made and the exact cause of shoulder pain was not established. Furthermore the HA injection was given at different sites. These facts makes the study less effective. The diagnosis and treatment should be more homogenous to provide potentially useful information for therapeutic recommendations.

Blaine et al [38] carried out a randomized, controlled trial to study the efficacy of sodium hyaluronate in the treatment of persistent shoulder pain. This was a multicentre study. The study included 660 randomized patients with moderate to severe shoulder pain that was refractory to standard treatment. They had three treatment groups namely the three-injection hyaluronate group, five-injection hyaluronate group, and phosphate-buffered saline solution group.

The majority (about 60%) of the patients in each treatment group had a diagnosis of osteoarthritis as the etiology of shoulder pain. Two thirds of these patients had concurrent shoulder abnormalities such as a partial or complete rotator cuff tear and/or adhesive capsulitis. The authors found that although the primary end point of this study was not achieved, the overall findings, including secondary end points, indicate that sodium hyaluronate is effective and well tolerated for the treatment of osteoarthritis and persistent shoulder pain that is refractory to other standard nonoperative interventions. The patients were not followed beyond twenty-six weeks, it is unclear how long the clinical benefit would have been maintained in these patients. The lack of fluoroscopic guidance may be considered a limitation of the study.

There, however, were glaring conflicts of interest in this study. The authors received editorial support in the preparation of this manuscript that was funded by the study sponsor i.e the manufacturers of sodium hyaluronate.

Harris et al [39] carried out a systematic review to study the efficacy of intra-articular hyaluronate injections for the treatment of adhesive capsulitis. The systematic review showed that sodium hyaluronate injection into the glenohumeral joint significantly improves shoulder range-of-motion, constant scores, and pain at short-term follow-up following treatment of adhesive capsulitis. They also found that isolated intra-articular hyaluronate injection has equivalent outcomes as compared to intra-articular corticosteroid injection. The study also showed that the improvement in range-of-motion following isolated hyaluronate injection was greater than control; however, the difference was not significant. There were several limitations in this study and one of the significant limiting factor in this review was the very short-term follow-up duration.


The prognosis of chronic shoulder pain depends to a large extent on the underlying cause of the pain. Generally, the pain responds well to conservative treatment [40,41]. Symptoms of gradual onset, more severe pain at presentation and prolonged symptoms are associated with a worse outcome for protracted recovery [42,43]. Generally, the speed of recovery in patients with chronic shoulder pain is slow. There are two prospective studies involving patients with chronic shoulder pain that have shown complete recovery at one month in 23 percent of patients, and at 18 months in 59 percent of patients [9,10].


Persistent shoulder pain is a common clinical problem. An estimated 20 percent of the population will suffer shoulder pain during their lifetime There are several causes of such persistent pain and these include glenohumeral osteoarthritis, rotator cuff tears, subacromial impingement, tendinitis, adhesive capsulitis, and subacromial bursitis. 

Effective treatment depends on an accurate diagnosis of the cause of the shoulder pain. Most patients respond to conservative treatment that involves activity modification, analgesic medications, and physical therapy. Failure to respond to these treatment modalities would be an indication for steroid injections. HA injections have no established role in the treatment of chronic shoulder pain. Surgery is rarely indicated.

Generally, the prognosis is good in most patients. Most patients recover within one to 18 months.


  1. Chakravarty K, Webley M. Shoulder joint movement and its relationship to disability in the elderly. J Rheumatol. 1993;20:1359-61.
  2. Steinfeld R, Valente RM, Stuart MJ. A commonsense approach to shoulder problems. Mayo Clin Proc. 1999;74:785-94.
  3. Pope DP, Croft PR, Pritchard CM, Silman AJ. Prevalence of shoulder pain in the community: the influence of case definition. Ann Rheum Dis. 199756(5):308–312.
  4. Andrews JR. Diagnosis and treatment of chronic painful shoulder: review of nonsurgical interventions. Arthroscopy. 2005;21:333-47.
  5. Roy A, Dahan THM, Belair M, Dahan B. Rotator cuff disease. eMedicine. http://www.emedicine.com/pmr/topic125.htm. 
  6. Sandor R. Adhesive capsulitis: optimal treatment of ‘frozen shoulder’. Phys Sportsmed. 2000;28:23-9.
  7. Siegel LB, Cohen NJ, Gall EP. Adhesive capsulitis: a sticky issue. Am Fam Physician. 1999;59:1843-52.
  8. Green S, Buchbinder R, Glazier R, Forbes A. Systematic review of randomised controlled trials of interventions for painful shoulder: selection criteria, outcome assessment, and efficacy. BMJ. 1998 Jan 31;316(7128):354-60. doi: 10.1136/bmj.316.7128.354. PMID: 9487172; PMCID: PMC2665551.
  9. Croft P, Pope D, Silman A. The clinical course of shoulder pain: prospective cohort study in primary care. Primary Care Rheumatology Society Shoulder Study Group. BMJ. 1996313(7057):601–602.
  10.  van der Windt DA, Koes BW, Boeke AJ, Deville W, De Jong BA, Bouter LM. Shoulder disorders in general practice: prognostic indicators of outcome. Br J Gen Pract. 199646(410):519–523.
  11. Ejnisman B, Andreoli CV, Soares BG, et al. Interventions for tears of the rotator cuff in adults. Cochrane Database Syst Rev. 2004;(1):CD002758.
  12. Green S, Buchbinder R, Hetrick S. Physiotherapy interventions for shoulder pain. Cochrane Database Syst Rev. 2003;(2):CD004258.
  13.  Calis M, Demir H, Ulker S, Kirnap M, Duygulu F, Calis HT. Is intraarticular sodium hyaluronate injection an alternative treatment in patients with adhesive capsulitis? Rheumatol Int. 2006 Apr;26(6):536-40. doi: 10.1007/s00296-005-0022-2. Epub 2005 Aug 10. PMID: 16091920.
  14.  Koester MC, Dunn WR, Kuhn JE, Spindler KP. The efficacy of subacromial corticosteroid injection in the treatment of rotator cuff disease: a systemic review. J Am Acad Orthop Surg. 200715(1):3–11.
  15.  Green S, Buchbinder R, Glazier R, Forbes A. Interventions for shoulder pain. Cochrane Database Syst Rev. 2000;(2):CD001156.
  16.  Arroll B, Goodyear-Smith F. Corticosteroid injections for painful shoulder: a meta-analysis. Br J Gen Pract. 200555(512):224–228.
  17.  Johansson K, Oberg B, Adolfsson L, Foldevi M. A combination of systematic review and clinicians' beliefs in interventions for subacromial pain. Br J Gen Pract. 200252(475):145–152.
  18.  Buchbinder R, Green S, Youd JM. Corticosteroid injections for shoulder pain. Cochrane Database Syst Rev. 2003;(1):CD004016.
  19.  Winters JC, Sobel JS, Groenier KH, Arendzen HJ, Meyboomde Jong B. Comparison of physiotherapy, manipulation, and corticosteroid injection for treating shoulder complaints in general practice: randomised, single blind study. BMJ. 1997314(7090):1320–1325.
  20.  van der Windt DA, Koes BW, Devillé W, et al. Effectiveness of corticosteroid injections versus physiotherapy for treatment of painful stiff shoulder in primary care: randomised trial. BMJ. 1998317(7168):1292–1296.
  21.  Koh KH. Corticosteroid injection for adhesive capsulitis in primary care: a systematic review of randomised clinical trials. Singapore Med J. 2016 Dec;57(12):646-657. doi: 10.11622/smedj.2016146. Epub 2016 Aug 29. PMID: 27570870; PMCID: PMC5165171.
  22.  Shah N. shoulder adhesive capsulitis: systematic review of randomized trials usig multiple corticoidsteroid injections. J Gen Pact. 2007;57:662-7
  23.  Management of Rotator Cuff Injuries- Evidence-Based Clinical Practice Guideline at https://www.aaos.org/globalassets/quality-and-practice-resources/rotator-cuff/rotator-cuff-cpg-final-12-20-19.pdf.
  24.  Carette S, Moffet H, Tardif J, et al. Intraarticular corticosteroids, supervised physiotherapy, or a combination of the two in the treatment of adhesive capsulitis of the shoulder: a placebo-controlled trial. Arthritis Rheum. 200348(3):829–838.
  25.  Self EB. Clinical guidelines for shoulder pain. In: Norris TR, ed. Orthopaedic Knowledge Update. Shoulder and Elbow 2. 2nd ed. Rosemont, Ill.: American Academy of Orthopaedic Surgeons, 2002:443–467.
  26.  Iannotti JP, Kwon YW. Management of persistent shoulder pain: a treatment algorithm. Am J Orthop. 200534(12 suppl):16–23.
  27.  Jacob AK, Sallay PI. Therapeutic efficacy of corticosteroid injections in the acromioclavicular joint. Biomed Sci Instrum. 199734:380–385.
  28.  Montellese P, Dancy T. The acromioclavicular joint. Prim Care. 200431(4):857–866.
  29.  Rabalais RD, McCarty E. Surgical treatment of symptomatic acromio-clavicular joint problems: a systematic review. Clin Orthop Relat Res. 2007455:30–37.
  30.  Griggs SM, Ahn A, Green A. Idiopathic adhesive capsulitis. A prospective functional outcome study of nonoperative treatment. J Bone Joint Surg Am. 2000;82-A(10):1398–1407.
  31.  Ryans I, Montgomery A, Galway R, Kernohan WG, McKane R. A randomized controlled trial of intra-articular triamcinolone and/or physiotherapy in shoulder capsulitis. Rheumatology (Oxford). 200544(4):529–535.
  32.  Wirth MA, Basamania C, Rockwood CA Jr. Nonoperative management of full-thickness tears of the rotator cuff. Orthop Clin North Am. 199728(1):59–67.
  33.  Mantone JK, Burkhead WZ Jr, Noonan J Jr. Nonoperative treatment of rotator cuff tears. Orthop Clin North Am. 200031(2):295–311.
  34.  Blair B, Rokito AS, Cuomo F, Jarolem K, Zuckerman JD. Efficacy of injections of corticosteroids for subacromial impingement syndrome. J Bone Joint Surg Am. 199678(11):1685–1689.
  35.  Bishop JY, Flatlow EL. Management of glenohumeral arthritis: a role for arthroscopy? Orthop Clin North Am. 200334(4):559–566.
  36.  Burkhead WZ Jr, Rockwood CA Jr. Treatment of instability of the shoulder with an exercise program. J Bone Joint Surg Am. 199274(6):890–896.
  37.  Saito et al. Therapeutic effects of hyaluronate injections in patients with chronic painful shoulder: a meta-analysis of randomized controlled trials. Arthritis Care and Research Vol 62 No 7 July 2010.
  38.  Blaine et al. Treatment of Persistent Shoulder Pain with Sodium Hyaluronate: A Randomized, Controlled Trial. A Multicenter Study. J Bone Joint Surg Am. 2008;90:970-9. 
  39.  Harris JD, Griesser MJ, Copelan A, Jones GL. Treatment of adhesive capsulitis with intra-articular hyaluronate: A systematic review. Int J Shoulder Surg. 2011;5(2):31-37.
  40.  Ginn KA, Cohen ML. Conservative treatment for shoulder pain: prognostic indicators of outcome. Arch Phys Med Rehabil. 200485(8):1231–1235.
  41.  Zheng X, Simpson JA, van der Windt DA, Elliott AM. Data from a study of effectiveness suggested potential prognostic factors related to the patterns of shoulder pain. J Clin Epidemiol. 200558(8):823–830.
  42. Kuijpers T, van der Windt DA, Boeke AJ, et al. Clinical prediction rules for the prognosis of shoulder pain in general practice. Pain. 2006120(3):276–285.
  43.  Thomas E, van der Windt DA, Hay EM, et al. Two pragmatic trials of treatment for shoulder disorders in primary care: generalisability, course, and prognostic indicators. Ann Rheum Dis. 200564(7):1056–1061.

Wednesday, 11 May 2022

               Treatment of fibromyalgia

                               Dr. KS Dhillon


Fibromyalgia is a common, debilitating, and often overlooked, clinical syndrome. It affects about 2% of the population with a peak incidence in middle-aged women (90.6%) [1]. Fibromyalgia overlaps with other functional somatic disorders, such as chronic fatigue syndrome, irritable bowel syndrome, and temporomandibular joint dysfunction [2]. Fibromyalgia commonly co-occurs with anxiety and mood disorders. Research shows that, although functional somatic disorders are related and potentially interact with psychological conditions, they are usually independent [3]. Fibromyalgia is characterised by features of widespread somatic pain and deep tissue tenderness. This results from sensitisation of neural pain pathways [4]. 

The patients can also have a variable combination of sleep disturbance, fatigue, cognitive dysfunction as well as psychological distress. These symptoms can be present despite the absence of objective abnormalities on clinical examination.

There is an incomplete understanding of this syndrome's pathogenesis. There is increasing evidence for a mechanism-based management approach to this syndrome [5,6]. These are likely to be more effective if introduced early, and this makes it important to make an early timely diagnosis. 


Fibromyalgia usually develops spontaneously [7]. It is likely to represent a maladaptive, stereotypical, biological response of the body to the cumulative effects of physical or psychological stress in people who are genetically predisposed to it [8]. It is also associated with psychiatric and musculoskeletal disorders, and that leads to poorer outcomes [9,10]. It can also occur after an infection.

The prevalence of fibromyalgia is increased in people with chronic medical disorders [11]. Fibromyalgia is primarily derived from pathophysiology within the central nervous system, where there is disordered sensory processing. There is growing evidence to suggest that fibromyalgia may comprise multiple pathogenetic subsets, including originating partly within the peripheral nervous system [4,12,13]. With time, most cases of fibromyalgia evolve out of persistent regional pain [14].


The fibromyalgia diagnostic criteria [15] have evolved from the recognition that fibromyalgia is a spectrum disorder, both with regards to spatial distribution of symptoms and pain severity. Diagnosing fibromyalgia can be challenging.

The condition should be considered as a possibility in all patients with persistent musculoskeletal pain, fatigue, or sleep disturbance, especially when such symptoms are out of proportion to the severity of any background chronic illness [16]. 

A practical, validated, self-assessment tool based on the diagnostic criteria has been developed [17] to quantitate the symptoms of fibromyalgia [18,19] (Table 1).

Scores above certain thresholds [19] yield reasonable sensitivity and specificity compared to the original classification criteria [20]. Other disorders that fully explain the patient's symptoms have to be excluded [21]. Examination for deep tissue tenderness, which was required by the old criteria, is now not needed. Investigations are needed to exclude treatable comorbidities and potential differential diagnoses, such as thyroid dysfunction [22].

                 Fibromyalgia survey questionnaire

I. Using the following scale, indicate for each item the level of severity over the past week by checking the appropriate box.

0: No problem

1: Slight or mild problems; generally mild or intermittent

2: Moderate; considerable problems; often present and/or at a moderate level

3: Severe; continuous, life-disturbing problems

Fatigue [ ] 0 [ ] 1 [ ] 2 [ ] 3

Trouble thinking or remembering [ ] 0 [ ] 1 [ ] 2 [ ] 3

Waking up tired (unrefreshed) [ ] 0 [ ] 1 [ ] 2 [ ] 3

II. During the past 6 months have you had any of the following symptoms?

Pain or cramps in the lower abdomen [ ] Yes [ ] No

Depression [ ] Yes [ ] No

Headache [ ] Yes [ ] No

III. Joint/body pain

Please indicate below if you have had pain or tenderness over the past 7 days in each of the areas listed below.

Please make an X in the box if you have had pain or tenderness. Be sure to mark both the right side and left side separately.

[] Shoulder, left [ ] Upper leg, left [ ] Lower back

[ ] Shoulder, right [ ] Upper leg, right [ ] Upper back

[ ] Hip, left [ ] Lower leg, left [ ] Neck

[ ] Hip, right [ ] Lower leg, right

[ ] Upper arm, left [ ] Jaw, left [ ] No pain in any of these areas

[ ] Upper arm, right [ ] Jaw, right

[ ] Lower arm, left [ ] Chest

[ ] Lower arm, right [ ] Abdomen

IV. Overall, were the symptoms listed in I–III above generally present for at least 3 months? [ ] Yes [ ] No

Table 1


Spontaneous recovery usually does not occur. The main aim of treatment is to improve symptoms, function, and quality of life [23]. The treatment is individually tailored. It is multimodal, multidisciplinary, and combines both pharmacological and non-pharmacological approaches [5].


Non-pharmacological approach

The medical treatment of fibromyalgia is usually only partially successful [5], hence health professionals need to give their patients sustained support to become active self-managers. This is the most important intervention to enable the patient to live successfully with this debilitating multidimensional disorder.  Self-management skill training is best delivered within a small group setting where education, training, coping skills, and cognitive behavioural approaches are explored [24]. Thereafter, skills can be consolidated by trained peer mentors [25]. For health professionals, an open and patient-centered communication style is recommended [26].

Among non-pharmacological therapies, exercise and psychoeducational approaches have the greatest evidence of efficacy [5]. Biomechanical assessment and subsequent exercise monitoring by a physical therapist is desirable. A referral to a psychologist should be considered in all patients, especially in those who are more psychologically distressed.

Pharmacological approach

Drug therapy has a supportive role in the management of symptoms. Some patients do not tolerate and others do not benefit from drugs. All drugs are started at low doses and gradually the dose is increased. The drugs are used to manage the patient's predominant symptoms such as pain, sleep disturbance, and psychological distress. The drugs are stopped if they provide no benefit.


Traditionally low-dose amitriptyline has been the first-line drug for treating pain and sleep disturbance in patients with fibromyalgia. The evidence supporting the use of amitriptyline is of low quality. 

A Cochrane Database Systematic  Review by Moore et al [27] showed that there was no first‐tier evidence on the efficacy of amitriptyline in fibromyalgia. There was some second-tier evidence that amitriptyline at 25 or 50 mg daily was better than placebo. About 64% of participants taking amitriptyline had adverse effects. Only about 38% of participants benefited from the use of amitriptyline. About 5% withdrew because of lack of efficacy with amitriptyline. Tolerance development and weight gain limit the use of amitriptyline. 

Serotonin and noradrenaline (norepinephrine) are mediators of descending inhibition in the nervous system. Their concentrations are reduced in patients with fibromyalgia. Hence, it is justified to have a trial of a serotonin noradrenaline reuptake inhibitor. In trials conducted by the manufacturers, there is low-quality evidence that Duloxetine at 60 mg per day is effective in the treatment of fibromyalgia [28].

Milnacipran as well inhibits the reuptake of serotonin and noradrenaline (norepinephrine). It can be used to treat fibromyalgia. The recommended dose is 100 mg daily in divided doses. There is some high-quality evidence which shows that it has modest efficacy [29].

Antiepileptic drugs

In patients with fibromyalgia, the concentrations of the pain facilitatory neurotransmitters glutamate and substance P in the central nervous system are elevated. These transmitters are the targets of gabapentin and pregabalin which have potential pain modulatory, sleep-promoting, and anxiolytic actions. 

A Cochrane Database Systematic  Review by Nurcan Üçeyler et al [30] showed that anticonvulsant, pregabalin, demonstrated a small benefit over placebo in reducing pain and sleep problems in patients with fibromyalgia. The amount and quality of evidence were insufficient to draw definite conclusions on the efficacy and safety of gabapentin, lacosamide, and levetiracetam in patients with fibromyalgia. 

Other drugs

There is weak evidence that NSAIDs are ineffective in the treatment of patients with fibromyalgia [5]. There is no trial evidence of efficacy for paracetamol used alone. There is preliminary evidence from randomized controlled trials of the efficacy of tramadol [31], pramipexole [32], and memantine [33]. Pure mu-opioid receptor agonists, such as codeine, oxycodone, and fentanyl are contraindicated because of poor clinical response and increased risk of opioid-induced hyperalgesia [31].  


Fibromyalgia can produce profound, multidimensional disability, and multidisciplinary management is required. A systematic, patient-centered approach can produce meaningful improvements in patient's symptoms, function as well as quality of life. Non-pharmacological treatments have an important role to play. Some drugs can complement an active rehabilitation program. There is some evidence for the use of amitriptyline, pregabalin, duloxetine, and milnacipran for the treatment of fibromyalgia. However, not all patients will benefit from these drugs. Patients should be monitored for adverse events resulting from the use of these drugs.


  1. Guymer EK, Littlejohn GO, Brand CK, Kwiatek RA. Fibromyalgia onset has a high impact on work ability in Australians. Intern Med J. 2016 Sep;46(9):1069-74. doi: 10.1111/imj.13135. PMID: 27242134.
  2. Kato K, Sullivan PF, Pedersen NL. Latent class analysis of functional somatic symptoms in a population-based sample of twins. J Psychosom Res 2010;68:447-53. http://dx.doi.org/10.1016/j.jpsychores.2010.01.010.
  3. Kato K, Sullivan PF, Evengård B, Pedersen NL. A population-based twin study of functional somatic syndromes. Psychol Med 2009;39:497-505. http://dx.doi.org/10.1017/ S0033291708003784. 
  4. Sluka KA, Clauw DJ. Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience 2016;338:114-29. https://doi.org/10.1016/j.neuroscience.2016.06.006.
  5. Macfarlane GJ, Kronisch C, Dean LE, Atzeni F, Häuser W, Fluß E, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis 2017;76:318-28. https://doi.org/10.1136/annrheumdis-2016-209724.
  6. Cochrane. Fibromyalgia. www.cochrane.org/search/site/fibromyalgia [cited 2017 Sep 1]
  7. Kashikar-Zuck S, Ting TV. Juvenile fibromyalgia: current status of research and future developments. Nat Rev Rheumatol. 2014;10(2):89-96. doi:10.1038/nrrheum.2013.177.
  8. Markkula R, Järvinen P, Leino-Arjas P, Koskenvuo M, Kalso E, Kaprio J. Clustering of symptoms associated with fibromyalgia in a Finnish Twin Cohort. Eur J Pain 2009;13:744-50. http://dx.doi.org/10.1016/j.ejpain.2008.09.007.
  9. Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature review. Arch Intern Med 2003;163:2433-45. https://doi.org/10.1001/archinte.163.20.2433.
  10.  Levy O, Segal R, Maslakov I, Markov A, Tishler M, Amit-Vazina M. The impact of concomitant fibromyalgia on visual analogue scales of pain, fatigue and function in patients with various rheumatic disorders. Clin Exp Rheumatol 2016;34 Suppl 96:S120-4.
  11. Wallit B, Nahin RL, Katz RS, Bergman MJ, Wolfe F. The prevalence and characteristics of fibromyalgia in the 2012 National Health Interview Survey. PLoS ONE 10:e0138024. https://doi.org/10.1371/journal.pone.0138024.
  12. Leinders M, Doppler K, Klein T, Deckart M, Rittner H, Sommer C, et al. Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome. Pain 2016;157:2493-503. https://doi.org/10.1097/j.pain.0000000000000668.
  13. . Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, et al. Gene expression alterations at baseline and following moderate exercise in patients with chronic fatigue syndrome and fibromyalgia syndrome. J Intern Med 2012;271:64-81. http://dx.doi.org/10.1111/j.1365-2796.2011.02405.x.
  14.  Bergman S, Herrström P, Jacobsson LT, Petersson IF. Chronic widespread pain: a three year followup of pain distribution and risk factors. J Rheumatol 2002;29:818-25. 
  15. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 2010;62:600-10. http://dx.doi.org/10.1002/acr.20140.
  16.  Guymer E, Littlejohn G. Fibromylagia. Aust Fam Physician 2013;42:690-4.
  17. Häuser W, Jung E, Erbslöh-Möller B, Gesmann M, Kühn-Becker H, Petermann F, et al. Validation of the Fibromyalgia Survey Questionnaire within a cross-sectional survey. PLoS One 2012;7:e37504. https://doi.org/10.1371/journal.pone.0037504.
  18. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RS, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol 2011;38:1113-22. http://dx.doi.org/10.3899/jrheum.100594
  19.  Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RL, et al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum 2016;46:319-29. https://doi.org/10.1016/j.semarthrit.2016.08.012.
  20. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 Criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160-72. http://dx.doi.org/10.1002/art.1780330203.
  21. Littlejohn G. Fibromyalgia: honing fibromyalgia diagnosis. Nat Rev Rheumatol 2014;10:267-9. http://dx.doi.org/10.1038/nrrheum.2014.48.
  22. Arnold LM, Clauw DJ, McCarberg BH; FibroCollaborative. Improving the recognition and diagnosis of fibromyalgia. Mayo Clin Proc 2011;86:457-64. https://doi.org/10.4065/mcp.2010.0738.
  23. Walitt B, Fitzcharles MA, Hassett AL, Katz RS, Häuser W, Wolfe F. The longitudinal outcome of fibromyalgia: a study of 1555 patients. J Rheumatol 2011;38:2238-46. http://dx.doi.org/10.3899/jrheum.110026.
  24. Bourgault P, Lacasse A, Marchand S, Courtemanche-Harel R, Charest J, Gaumond I, et al. Multicomponent interdisciplinary group intervention for self-management of fibromyalgia: a mixed-methods randomized controlled trial. PLoS One 2015;10:e0126324. https://doi.org/10.1371/journal.pone.0126324
  25. . Harris J, Williams T, Hart O, Hanson C, Johnstone G, Muthana A, et al. Using health trainers to promote selfmanagement of chronic pain: can it work? Br J Pain 2014;8:27-33. https://doi.org/10.1177/2049463713511956
  26. Ullrich A, Hauer J, Farin E. Communication preferences in patients with fibromyalgia syndrome: descriptive results and patient characteristics as predictors. Patient Prefer Adherence 2014;8:135-45. http://dx.doi.org/10.2147/PPA.S53474
  27. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2012 Dec 12;12:CD008242. doi: 10.1002/14651858.CD008242.pub2. Update in: Cochrane Database Syst Rev. 2015;7:CD008242. PMID: 23235657.
  28. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014 Jan 3;(1):CD007115. doi: 10.1002/14651858.CD007115.pub3. PMID: 24385423.
  29. Cording M, Derry S, Phillips T, Moore RA, Wiffen PJ. Milnacipran for pain in fibromyalgia in adults. Cochrane Database Syst Rev 2015;10:CD008244. https://doi.org/10.1002/14651858.CD008244.pub3
  30. Üçeyler N, Sommer C, Walitt B, Häuser W. Anticonvulsants for fibromyalgia. Cochrane Database Syst Rev. 2013 Oct 16;(10):CD010782. doi: 10.1002/14651858.CD010782. Update in: Cochrane Database Syst Rev. 2017 Oct 09;10 :CD010782. PMID: 24129853.
  31. Littlejohn GO, Guymer EK, Ngian GS. Is there a role for opioids in the treatment of fibromyalgia? Pain Manag 2016;6:347-55. http://dx.doi.org/10.2217/pmt-2016-0012.
  32.  Holman AJ, Myers RR. A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications. Arthritis Rheum 2005;52:2495-505. http://dx.doi.org/10.1002/art.21191.
  33.  Olivan-Blázquez B, Herrera-Mercadal P, Puebla-Guedea M, Pérez-Yus MC, Andrés E, Fayed N, et al. Efficacy of memantine in the treatment of fibromyalgia: a double-blind, randomised, controlled trial with 6-month follow-up. Pain 2014;155:2517-25. http://dx.doi.org/10.1016/j.pain.2014.09.004.