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Chronic Pain


James C. Watson

, MD, Mayo Clinic College of Medicine and Science

Reviewed/Revised Mar 2022 | Modified Sep 2022
Topic Resources

Chronic pain is pain that persists or recurs for > 3 months, persists > 1 month after resolution of an acute tissue injury, or accompanies a nonhealing lesion. Causes include chronic disorders (eg, cancer, arthritis, diabetes), injuries (eg, herniated disk, torn ligament), and many primary pain disorders (eg, neuropathic pain, fibromyalgia, chronic headache). Various drugs and psychologic treatments are used.

Unresolved, long-lasting disorders (eg, cancer, rheumatoid arthritis, herniated disk) that produce ongoing nociceptive stimuli may account completely for chronic pain. Alternatively, injury, even mild injury, may lead to long-lasting changes (sensitization) in the nervous system—from peripheral receptors to the cerebral cortex—that may produce persistent pain in the absence of ongoing nociceptive stimuli. With sensitization, discomfort that is due to a nearly resolved disorder and might otherwise be perceived as mild or trivial is instead perceived as significant pain.

In some cases (eg, chronic back pain after injury), the original precipitant of pain is obvious; in others (eg, chronic headache, atypical facial pain, chronic abdominal pain Chronic Abdominal Pain and Recurrent Abdominal Pain Chronic abdominal pain (CAP) is pain that persists for more than 3 months either continuously or intermittently. Intermittent pain may be referred to as recurrent abdominal pain (RAP). Acute... read more ), the precipitant is remote or occult.

Psychologic factors may amplify persistent pain. Thus, chronic pain may appear out of proportion to identifiable physical processes. Chronic pain commonly leads to or exacerbates psychologic problems (eg, depression, anxiety). Distinguishing psychologic cause from effect is often difficult, but if pain, depression, and anxiety co-exist, they typically intensify the overall pain experience.

Various factors in the patient’s environment (eg, family members, friends) may reinforce behaviors that perpetuate chronic pain.


Fibromyalgia Fibromyalgia Fibromyalgia is a common, incompletely understood nonarticular, noninflammatory disorder characterized by generalized aching (sometimes severe); widespread tenderness of muscles, areas around... read more is the most common chronic widespread pain syndrome. Prevalence is 2 to 3%. It is more common among women; however, with the newer diagnostic criteria, which de-emphasizes the need for a set number of local tender points, more men are now being diagnosed with fibromyalgia than in the past and the gender gap has decreased.

The pathophysiology is unknown, but a central sensitization syndrome with impairment of pain regulation may be involved, and the nociceptive pathways and processing centers are primed and over-reactive to stimuli.

Fibromyalgia reference

  • 1. Galvez-Sánchez CM, A. Reyes del Paso GA: Diagnostic criteria for fibromyalgia: Critical review and future perspectives. J Clin Med 9 (4): 1219, 2020. Published online 2020 Apr 23. doi: 10.3390/jcm9041219

  • 2. Häuser W, Brähler E, Ablin J, Wolfe F: Modified 2016 American College of Rheumatology fibromyalgia criteria, the analgesic, anesthetic, and addiction clinical trial translations innovations opportunities and networks–American Pain Society Pain Taxonomy, and the Prevalence of Fibromyalgia. Arthritis Care & Research 73 (5): 617–625, 2021.

Symptoms and Signs of Chronic Pain

Chronic pain often leads to vegetative signs (eg, lassitude, sleep disturbance, decreased appetite, loss of taste for food, weight loss, diminished libido, constipation), which develop gradually. Constant, unremitting pain may lead to depression and anxiety and interfere with almost all activities. Patients may become inactive, withdraw socially, and become preoccupied with physical health. Psychologic and social impairment may be severe, causing virtual lack of function.

Diagnosis of Chronic Pain

  • Evaluation for physical cause initially and if symptoms change

The etiology of chronic pain should be evaluated appropriately and characterized to, if possible, arrive at a diagnosis. However, once a full evaluation is done, repeating tests in the absence of new findings is not useful. The best approach is often to stop testing and focus on relieving pain and restoring function.

The effect of pain on the patient’s life should be evaluated; evaluation by an occupational therapist may be necessary. Formal psychiatric evaluation should be considered if a coexisting psychiatric disorder (eg, major depression Major depressive disorder (unipolar depressive disorder) Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more , an anxiety disorder Overview of Anxiety Disorders Anxiety disorders are characterized by persistent and excessive fear and anxiety and the dysfunctional behavioral changes a patient may use to mitigate these feelings. Anxiety disorders are... read more ) is suspected as cause or effect. Pain relief and functional improvement are unlikely if concomitant psychiatric disorders are not managed.

Treatment of Chronic Pain

  • Often multimodal therapy (eg, analgesics, physical methods, psychologic treatments)

Specific causes of chronic pain should be treated. Early, aggressive treatment of acute pain is always preferable and may limit or prevent sensitization and remodeling and thus prevent progression to chronic pain. However, once chronic pain is established and persists, multimodal treatment strategies are needed. Drugs or physical methods may be used; psychologic and behavioral therapies are usually helpful.

If patients have marked functional impairment or do not respond to a reasonable attempt at management by their physician, they may benefit from the multidisciplinary approach available at a pain clinic. Goals shift from totally eliminating pain to limiting its effects and optimizing function and quality of life.


Analgesics include

Use of one or more drugs with different mechanisms of action (rational polypharmacy) is often necessary for chronic pain. Adjuvant analgesics are most commonly used for neuropathic pain.

Opioid analgesics are useful in managing chronic pain due to cancer or other terminal disorders. There is insufficient evidence to support opioid therapy for long-term management of chronic pain due to nonterminal disorders; nondrug and nonopioid drug treatments are generally preferred. However, for persistent, moderate-to-severe pain that impairs function, opioids may be considered, usually as adjunctive therapy, when potential benefits are expected to exceed risks. Opioids should not be used to manage fibromyalgia.

The Centers for Disease Control and Prevention (CDC) has published guidelines for prescribing opioids for chronic pain.

Factors to consider before prescribing opioids include the following:

If opioids are prescribed for chronic pain, physicians should take several steps:

  • Provide education and counseling: Patients should be counseled about the risks of combining opioids with alcohol and anxiolytics and of self-adjusting dosing. Patients should be taught about the need for safe, secure storage and ways to correctly dispose of unused drugs. They should be instructed not to share opioids and to contact their physician if they experience sedation.

  • Assess risk factors for misuse, diversion, and abuse: Risk factors include prior or current alcohol or drug abuse; family history of alcohol or drug abuse; and a prior or current major psychiatric disorder. Presence of risk factors does not always contraindicate opioid use. However, if patients have risk factors, they should be referred to a pain management specialist, or the physician should take special precautions to deter misuse, diversion, and abuse; these measures can include prescribing only small amounts (requiring frequent visits for refills), not refilling prescriptions allegedly lost, and using urine drug screening before first prescribing opioids and periodically (eg, at least yearly) thereafter to confirm that the prescribed opioid is being taken and not diverted to others.

  • Check data in monitoring programs for controlled substance use: The patient's history of controlled substance use can be reviewed through state prescription drug monitoring programs (PDMPs). Current recommendations are to screen with the PDMP when prescribing opioids initially and when refilling each prescription or at least every 3 months.

  • Have the patient sign an opioid contract and give informed consent: An opioid contract includes safety precautions for prescribing opioids, the patient's responsibilities to ensure safe use, and measures to prevent aberrant use (ie, opioid tapering). Informed consent is obtained, when possible, to help clarify the goals, expectations, and risks of treatment, as well as the possible use of nonopioid treatment alternatives.

Current guidelines emphasize that when starting opioids for chronic pain, clinicians should prescribe immediate-release opioids instead of long-acting opioids (1 Treatment reference Chronic pain is pain that persists or recurs for > 3 months, persists > 1 month after resolution of an acute tissue injury, or accompanies a nonhealing lesion. Causes include chronic disorders... read more ). Also, using the lowest effective dose (even for immediate-release opioids) is preferred over transitioning to a long-acting opioid (see tables Opioid Analgesics Opioid Analgesics Opioid Analgesics and Equianalgesic Doses of Opioid Analgesics Equianalgesic Doses of Opioid Analgesics*,† Equianalgesic Doses of Opioid Analgesics*,† ). Previously, long-acting opioids were preferred to immediate-release opioids for the treatment of chronic pain; however, doses of long-acting opioids are often higher, and they may have more adverse effects and greater potential for misuse.

  • Limiting total daily oral morphine milligram equivalents (OMME Equianalgesic Doses of Opioid Analgesics*,† Equianalgesic Doses of Opioid Analgesics*,† ) to < 50 when possible

  • Considering the individual harm/benefit ratio at doses > 50 OMME daily

  • When possible, avoiding doses > 90 OMME daily

  • Weighing the needs for analgesia and functional improvement against the risks of higher-dose therapy before justifying daily doses > 90 OMME

  • Tapering and then stopping opioid therapy if the goals for pain relief and functional improvement are not met or if maintaining them requires dose escalation

Buprenorphine or methadone should be prescribed only by clinicians trained in the unique qualities and risks of these drugs.

Follow-up includes regularly reassessing the extent of pain reduction, functional improvement, and adverse effects and checking for signs suggesting misuse, diversion, or abuse. For example, patients should be reassessed within 4 weeks of starting opioids, when the dose is increased, and at least every 3 months.

Potential benefits and risks of opioid dose should be reassessed if the opioid dose exceeds 50 mg OMME/day. Doses exceeding 90 mg OMME/day should be avoided when possible.

Naloxone should be considered if patients are at risk of overdose but still require opioid therapy: Clinicians should discuss the risks of overdose and respiratory depression with the patient and family members. Risk factors for overdose include comorbidities, unavoidable concomitant drug usage (eg, benzodiazepines), prior history of overdose or substance use disorder, and use of high-dose opioids (≥ 50 OMME). The patient and family members should be taught how to administer naloxone.

Opioids have different potencies based on their ability to bind to opioid receptors and the efficiency of oral absorption of the opioid versus direct injection into the vasculature. Understanding 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. For example, 30 mg of oral morphine is equivalent to

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

  • 20 mg of oral oxycodone

  • 7.5 mg of oral hydromorphone

To allow comparison of opioid use and risk, clinicians should consider the overall dosage of different forms as a uniform variable. The Centers for Disease Control and Prevention (CDC) structured its guidelines for opioid use and risk around the daily oral morphine milligram equivalents (OMME) taken by a patient. For example, a patient taking 10 mg of oral oxycodone 4 times a day is taking 40 mg of oral oxycodone a day. Based on the equianalgesic dosage conversion in the table below (20 mg oral oxycodone equals 30 mg of oral morphine), 40 mg of oral oxycodone is equivalent to 60 mg of oral morphine a day (60 mg OMME). A patient taking 4 mg of oral hydromorphone 4 times a day (16 mg a day) is taking an OMME of 64 mg (from the table below); 7.5 mg of oral hydromorphone equals 30 mg of oral morphine (simplified to 1 mg of oral hydromorphone equals 4 mg of oral morphine).


As pain lessens, patients usually need help reducing use of opioids. If depression coexists with pain, antidepressants should be used.

Physical methods

Integrative medicine techniques

Integrative medicine techniques Overview of Integrative, Complementary, and Alternative Medicine Integrative medicine and health (IMH) and complementary and alternative medicine (CAM) include healing approaches and therapies that historically have not been included in conventional, mainstream... read more (previously called complementary and alternative medicine) can often be used to treat chronic pain. Techniques include acupuncture Acupuncture Acupuncture, a therapy within traditional Chinese medicine, is one of the most widely accepted components of integrative therapies in the western world. Specific points on the body are stimulated... read more , mind-body techniques (eg, meditation Meditation In meditation, a type of mind-body medicine, patients regulate their attention or systematically focus on particular aspects of inner or outer experience. The most highly studied forms of meditation... read more , yoga, tai chi), manipulation and body-based therapies (eg, chiropractic Chiropractic In chiropractic (a manipulative and body-based practice), the relationship between the structure of the spine and other articulating surfaces and their interaction with the nervous system is... read more or osteopathic manipulation, massage therapy Massage Therapy In massage therapy (a manipulative and body-based practice), body tissues are manipulated to reduce pain, relieve muscle tension, and reduce stress. The therapeutic value of massage for many... read more ), and energy-based therapies (eg, therapeutic touch Therapeutic Touch Therapeutic touch is a type of energy medicine. The philosophy behind this modality is to use the therapist’s energy (biofield) to influence the patient’s biofield. Usually, practitioners do... read more , reiki Reiki Reiki, which originated in Japan, is a type of energy medicine. In Reiki, practitioners intend to channel energy through their hands and transfer it into the patient’s body to promote healing... read more ).

Psychologic and behavioral therapies

Behavioral therapy can improve patient function, even without reducing pain. Patients should keep a diary of daily activities to pinpoint areas amenable to change. The physician should make specific recommendations for gradually increasing physical activity and social engagement. Activities should be prescribed in gradually increasing units of time; pain should not, if at all possible, be allowed to abort the commitment to greater function. When activities are increased in this way, reports of pain often decrease.

Behavior of family members or fellow workers that reinforces pain behavior (eg, constant inquiries about the patient’s health or insistence that the patient do no chores) should be discouraged. The physician should avoid reinforcing pain behavior, discourage maladaptive behaviors, applaud progress, and provide pain treatment while emphasizing return of function.

Pain rehabilitation programs

Pain rehabilitation programs are multidisciplinary programs for patients with chronic pain. These programs include education, cognitive-behavioral therapy, physical therapy, drug regimen simplification, and sometimes detoxification and tapering of analgesics. They focus on

  • Restoring function

  • Improving quality of life

  • Helping patients control their own life, despite chronic pain

Treatment reference

  • 1. Centers for Disease Control and Prevention: 2019 Annual surveillance report of drug-related risks and outcomes—United States. Surveillance special report. Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. Published August 31, 2018. Accessed 9/21/21.

Key Points

  • Nociceptive stimuli, sensitization of the nervous system, and psychologic factors can contribute to chronic pain.

  • Distinguishing between the psychologic causes and effects of chronic pain may be difficult.

  • Seek a physical cause even if psychologic factors are prominent, and always evaluate the effect of pain on the patient's life.

  • Treat poorly controlled pain with multimodal therapy (eg, appropriate physical, psychologic, behavioral, and interventional treatments; drugs).

More Information

  • CDC guideline for prescribing opioids for chronic pain: Goals of the guideline are to explain the benefits and risks of opioids for chronic pain, to make the treatment of chronic pain safer and more effective, and to reduce risks of long-term opioid treatment. Recommendations include preferentially using nonopioid therapy for managing chronic pain, using opioids only when benefits are expected to outweigh risks, establishing treatment goals with patients before starting opioids, and prescribing the lowest effective dosage.

Drugs Mentioned In This Article

Drug Name Select Trade
ARYMO ER, Astramorph PF, Avinza, DepoDur, Duramorph PF, Infumorph, Kadian, MITIGO, MORPHABOND, MS Contin, MSIR, Opium Tincture, Oramorph SR, RMS, Roxanol, Roxanol-T
Belbuca, Brixadi, Buprenex, Butrans, Probuphine, Sublocade, Subutex
Dolophine, Methadose
EVZIO, Kloxxado, Narcan, ZIMHI
Dazidox , Endocodone , ETH-Oxydose, Oxaydo, OXECTA, OxyContin, Oxydose , OxyFast, OxyIR, Percolone, Roxicodone, Roxybond, XTAMPZA
Dilaudid, Dilaudid-HP, Exalgo, Palladone, Simplist Dilaudid
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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