Chronic pain is pain that lasts a long time. In medicine, the distinction between acute and chronic pain is sometimes determined by an arbitrary interval of time since onset; the two most commonly used markers being 3 months and 6 months since onset, though some theorists and researchers have placed the transition from acute to chronic pain at 12 months. Others apply acute to pain that lasts less than 30 days, chronic to pain of more than six months duration, and subacute to pain that lasts from one to six months. A popular alternative definition of chronic pain, involving no arbitrarily fixed duration, is "pain that extends beyond the expected period of healing". Epidemiological studies have found that 10.1% to 55.2% of people in various countries have chronic pain.
Chronic pain may originate in the body, or in the brain or spinal cord. It is often difficult to treat. Various nonopioid medicines are recommended initially, depending on whether the pain originates from tissue damage or is neuropathic. Psychological treatments including cognitive behavioral therapy and acceptance and commitment therapy may be effective for improving quality of life in those with chronic pain. Some people with chronic pain may benefit from opioid treatment while others are harmed. In people with non-cancer pain, a trial of opioids is only recommended if there is no history of either mental illness or substance use disorder and should be stopped if not effective.
Severe chronic pain is associated with increased 10 year mortality, particularly from heart disease and respiratory disease. People with chronic pain tend to have higher rates of depression, anxiety, and sleep disturbances; these are correlations and it is often not clear which factor causes another. Chronic pain may contribute to decreased physical activity due to fear of exacerbating pain, often resulting in weight gain. Pain intensity, pain control, and resiliency to pain are influenced by different levels and types of social support that a person with chronic pain receives.
The International Association for the study of pain defines chronic pain as pain with no biological value, that persists past normal tissue healing. The DSM-5 recognizes one chronic pain disorder, somatic symptom disorders, a reduction from the three previously recognized pain disorders. The criteria include it lasting for greater than six months.
The suggested ICD-11 chronic pain classification suggests 7 categories for chronic pain.
- Chronic primary pain: defined by 3 months of persistent pain in one or more anatomical regions that is unexplainable by another pain condition.
- Chronic cancer pain: defined as cancer or treatment related visceral, musculoskeletal, or bony pain.
- Chronic posttraumatic pain: pain lasting 3 months post trauma or surgery, excluding infectious or preexisting conditions.
- Chronic neuropathic pain: pain caused by damage to the somatosensory nervous system damage.
- Chronic headache and orofacial pain: pain that originates in the head or face, and occurs for 50% or more days over a 3 months period.
- Chronic visceral pain: pain originating in an internal organ.
- Chronic musculoskeletal pain: pain originating in the bones, muscles, joints or connective tissue.
Chronic pain may be divided into "nociceptive" (caused by inflamed or damaged tissue activating specialised pain sensors called nociceptors), and "neuropathic" (caused by damage to or malfunction of the nervous system).
Nociceptive pain may be divided into "superficial" and "deep", and deep pain into "deep somatic" and "visceral". Superficial pain is initiated by activation of nociceptors in the skin or superficial tissues. Deep somatic pain is initiated by stimulation of nociceptors in ligaments, tendons, bones, blood vessels, fasciae and muscles, and is dull, aching, poorly-localized pain. Visceral pain originates in the viscera (organs). Visceral pain may be well-localized, but often it is extremely difficult to locate, and several visceral regions produce "referred" pain when damaged or inflamed, where the sensation is located in an area distant from the site of pathology or injury.
Neuropathic pain is divided into "peripheral" (originating in the peripheral nervous system) and "central" (originating in the brain or spinal cord). Peripheral neuropathic pain is often described as "burning", "tingling", "electrical", "stabbing", or "pins and needles".
Under persistent activation nociceptive transmission to the dorsal horn may induce a pain wind-up phenomenon. This induces pathological changes that lower the threshold for pain signals to be transmitted. In addition it may generate nonnociceptive nerve fibers to respond to pain signals. Nonnociceptive nerve fibers may also be able to generate and transmit pain signals. The type of nerve fibers that are believed to propagate the pain signals are the C-fibers, since they have a slow conductivity and give rise to a painful sensation that persists over a long time. In chronic pain this process is difficult to reverse or eradicate once established. In some cases, chronic pain can be caused by genetic factors which interfere with neuronal differentiation, leading to a permanent reduction in the threshold for pain.
Chronic pain of different etiologies has been characterized as a disease affecting brain structure and function. Magnetic resonance imaging studies have shown abnormal anatomical and functional connectivity, even during rest involving areas related to the processing of pain. Also, persistent pain has been shown to cause grey matter loss, reversible once the pain has resolved.
These structural changes can be explained by the phenomenon known as neuroplasticity. In the case of chronic pain, the somatotopic representation of the body is inappropriately reorganized following peripheral and central sensitization. This maladaptive change results in the experience of allodynia or hyperalgesia. Brain activity in individuals with chronic pain, measured via electroencephalogram (EEG), has been demonstrated to be altered, suggesting pain-induced neuroplastic changes. More specifically, the relative beta activity (compared to the rest of the brain) is increased, the relative alpha activity is decreased, and the theta activity both absolutely and relatively is diminished.
Dopaminergic dysfunction has been hypothesized to act as a shared mechanism between chronic pain, insomnia and major depressive disorder. Increased tonic dopamine activity and a compensatory decrease in phasic dopamine activity, which is important in inhibiting pain. This is supported by the implication of COMT in fibromyalgia and temporomandibular joint syndrome. Astrocytes, microglia, and Satellite glial cells have been found to be dysfunctional in chronic pain. Increased activity of microglia, alterations of microglial networks as well as increased production of chemokines and cytokines by microglia are proposed to act to potentiate pain. Astrocytes have been observed to lose their ability to regulate the excitability of neurons, increasing spontaneous neural activity in pain circuits.
Pain management is the branch of medicine employing an interdisciplinary approach to the relief of pain and improvement in the quality of life of those living with pain. The typical pain management team includes medical practitioners (particularly anesthesiologists), clinical psychologists, physiotherapists, occupational therapists, physician assistants, and nurse practitioners. Acute pain usually resolves with the efforts of one practitioner; however, the management of chronic pain frequently requires the coordinated efforts of the treatment team. Complete and sustained remission of many types of chronic pain is rare, though some can be done to improve quality of life.
Initially recommended efforts are non opioid based therapies.
Various nonopioid medicines are used, depending on whether the pain originates from tissue damage or is neuropathic. Limited evidence suggests that chronic pain from tissue inflammation or damage (as in rheumatoid arthritis and cancer pain) is best treated with opioids, while for neuropathic pain (pain caused by a damaged or dysfunctional nervous system) other drugs may be more effective, such as tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and anticonvulsants. Because of weak evidence, the best approach is not clear when treating many types of pain, and doctors must rely on their own clinical experience. Doctors often cannot predict who will use opioids just for pain management and who will go on to develop addiction, and cannot always distinguish between those who are and those who are not seeking opioids due primarily to an existing addiction. Withholding, interrupting or withdrawing opioid treatment in people who benefit from it can cause harm.
Interventional pain management may be appropriate, including techniques such as trigger point injections, neurolytic blocks, and radiotherapy. While there is no high quality evidence to support ultrasound, it has been found to have a small effect on improving function in non-specific chronic low back pain.
Psychological treatments, including cognitive behavioral therapy and acceptance and commitment therapy have been shown effective for improving quality of life and reducing pain interference in those with chronic pain.
In those who have not benefited from other measures and have no history of either mental illness or substance use disorder treatment with opioids may be tried. If significant benefit does not occur it is recommended that they be stopped. In those on opioids, stopping or decreasing their use may improve outcomes including pain.
Some people with chronic pain benefit from opioid treatment and others do not; some are harmed by the treatment. Possible harms include reduced sex hormone production, hypogonadism, infertility, impaired immune system, falls and fractures in older adults, neonatal abstinence syndrome, heart problems, sleep-disordered breathing, opioid-induced hyperalgesia, physical dependence, addiction, and overdose.
Preliminary studies have found medical marijuana to be beneficial in treating neuropathic pain, but not other kinds of long term pain. As of 2018 even for neuropathic pain the evidence is not strong for any benefit and further research is needed.
Tai Chi has been shown to improve pain, stiffness, and quality of life in chronic conditions such as osteoarthritis, low back pain, and osteoporosis. Acupuncture has also been found to be an effective and safe treatment in reducing pain and improving quality of life in chronic pain including chronic pelvic pain syndrome.
A systematic literature review of chronic pain found that the prevalence of chronic pain varied in various countries from 10.1% to 55.2% of the population, affected women at a higher rate than men, and that chronic pain consumes a large amount of healthcare resources around the globe.
A large-scale telephone survey of 15 European countries and Israel, 19% of respondents over 18 years of age had suffered pain for more than 6 months, including the last month, and more than twice in the last week, with pain intensity of 5 or more for the last episode, on a scale of 1 (no pain) to 10 (worst imaginable). 4839 of these respondents with chronic pain were interviewed in depth. Sixty six percent scored their pain intensity at moderate (5–7), and 34% at severe (8–10); 46% had constant pain, 56% intermittent; 49% had suffered pain for 2–15 years; and 21% had been diagnosed with depression due to the pain. Sixty one percent were unable or less able to work outside the home, 19% had lost a job, and 13% had changed jobs due to their pain. Forty percent had inadequate pain management and less than 2% were seeing a pain management specialist.
In the United States, the prevalence of chronic pain has been estimated to be approximately 35%, with approximately 50 million Americans experiencing partial or total disability as a consequence. According to the Institute of Medicine, there are about 116 million Americans living with chronic pain, which suggests that approximately half of American adults have some chronic pain condition. The Mayday Fund estimate of 70 million Americans with chronic pain is slightly more conservative. In an internet study, the prevalence of chronic pain in the United States was calculated to be 30.7% of the population: 34.3% for women and 26.7% for men.
Chronic pain is associated with higher rates of depression and anxiety.[unreliable medical source?] Sleep disturbance, and insomnia due to medication and illness symptoms are often experienced by those with chronic pain. Chronic pain may contribute to decreased physical activity due to fear of exacerbating pain, often resulting in weight gain.[unreliable medical source?] Such co-morbidities can be difficult to treat due to the high potential of medication interactions, especially when the conditions are treated by different doctors.
Severe chronic pain is associated with increased 10 year mortality, particularly from heart disease and respiratory disease. Several mechanisms have been proposed for the increased mortality, e.g. abnormal endocrine stress response. Additionally, chronic stress seems to affect cardiovascular risk by acceleration of the atherosclerotic process. However, further research is needed to clarify the relationship between severe chronic pain, stress and cardiovascular health.
Two of the most frequent personality profiles found in people with chronic pain by the Minnesota Multiphasic Personality Inventory (MMPI) are the conversion V and the neurotic triad. The conversion V personality, so called because the higher scores on MMPI scales 1 and 3, relative to scale 2, form a "V" shape on the graph, expresses exaggerated concern over body feelings, develops bodily symptoms in response to stress, and often fails to recognize their own emotional state, including depression. The neurotic triad personality, scoring high on scales 1, 2 and 3, also expresses exaggerated concern over body feelings and develops bodily symptoms in response to stress, but is demanding and complaining.
Some investigators have argued that it is this neuroticism that causes acute pain to turn chronic, but clinical evidence points the other way, to chronic pain causing neuroticism. When long term pain is relieved by therapeutic intervention, scores on the neurotic triad and anxiety fall, often to normal levels. Self-esteem, often low in people with chronic pain, also shows striking improvement once pain has resolved.
It has been suggested that catastrophizing may play a role in the experience of pain. Pain catastrophizing is the tendency to describe a pain experience in more exaggerated terms than the average person, to think a great deal more about the pain when it occurs, or to feel more helpless about the experience. People who score highly on measures of catastrophization are likely to rate a pain experience as more intense than those who score low on such measures. It is often reasoned that the tendency to catastrophize causes the person to experience the pain as more intense. One suggestion is that catastrophizing influences pain perception through altering attention and anticipation, and heightening emotional responses to pain. However, at least some aspects of catastrophization may be the product of an intense pain experience, rather than its cause. That is, the more intense the pain feels to the person, the more likely they are to have thoughts about it that fit the definition of catastrophization.
Social support has important consequences for individuals with chronic pain. In particular, pain intensity, pain control, and resiliency to pain has been implicated as outcomes influenced by different levels and types of social support. Much of this research has focused on emotional, instrumental, tangible and informational social support. People with persistent pain conditions tend to rely on their social support as a coping mechanism and therefore have better outcomes when they are a part of larger more supportive social networks. Across a majority of studies investigated, there was a direct significant association between social activities or social support and pain. Higher levels of pain were associated with a decrease in social activities, lower levels of social support, and reduced social functioning.
Effect on cognition
Chronic pain's impact on cognition is an under-researched area, but several tentative conclusions have been published. Most people with chronic pain complain of cognitive impairment, such as forgetfulness, difficulty with attention, and difficulty completing tasks. Objective testing has found that people in chronic pain tend to experience impairment in attention, memory, mental flexibility, verbal ability, speed of response in a cognitive task, and speed in executing structured tasks.
- Turk, D.C.; Okifuji, A. (2001). "Pain terms and taxonomies". In Loeser, D.; Butler, S. H.; Chapman, J.J.; Turk, D. C. Bonica's Management of Pain (3rd ed.). Lippincott Williams & Wilkins. pp. 18–25. ISBN 978-0-683-30462-6.
- Main, C.J.; Spanswick, C.C. (2001). Pain management: an interdisciplinary approach. Elsevier. p. 93. ISBN 978-0-443-05683-3.
- Thienhaus, O.; Cole, B.E. (2002). "Classification of pain". In Weiner, R.S. Pain management: A practical guide for clinicians (6 ed.). American Academy of Pain Management. ISBN 978-0-8493-0926-7.
- Harstall C, Ospina M. How Prevalent Is Chronic Pain? June 2003 volume XI issue2 Pain Clinical Updates, International Association for the Study of Pain. pages=1–4 
- Tauben D (2015). "Nonopioid medications for pain". Phys Med Rehabil Clin N Am. 26 (2): 219–48. doi:10.1016/j.pmr.2015.01.005. PMID 25952062.
- Welsch P, Sommer C, Schiltenwolf M, Häuser W (2015). "[Opioids in chronic noncancer pain-are opioids superior to nonopioid analgesics? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids versus nonopioid analgesics of at least four week's duration]". Schmerz (in German). 29 (1): 85–95. doi:10.1007/s00482-014-1436-0. PMID 25376546.
- Reuben, DB; H Alvanzo, AA; Ashikaga, T; Bogat, GA; Callahan, CM; Ruffing, V; Steffens, DC (13 January 2015). "National Institutes of Health Pathways to Prevention Workshop: The Role of Opioids in the Treatment of Chronic Pain". Annals of Internal Medicine. 162 (4): 295–300. doi:10.7326/M14-2775. PMID 25581341.
- Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, Dana T, Bougatsos C, Deyo RA (2015). "The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop". Ann. Intern. Med. 162 (4): 276–86. doi:10.7326/M14-2559. PMID 25581257.
- Busse, JW; Craigie, S; Juurlink, DN; Buckley, DN; Wang, L; Couban, RJ; Agoritsas, T; Akl, EA; Carrasco-Labra, A; Cooper, L; Cull, C; da Costa, BR; Frank, JW; Grant, G; Iorio, A; Persaud, N; Stern, S; Tugwell, P; Vandvik, PO; Guyatt, GH (8 May 2017). "Guideline for opioid therapy and chronic noncancer pain". CMAJ : Canadian Medical Association Journal. 189 (18): E659–E666. doi:10.1503/cmaj.170363. PMC 5422149. PMID 28483845.
- Katz, Joel; Rosenbloom, Brittany N; Fashler, Samantha (2 February 2017). "Chronic Pain, Psychopathology, and DSM-5 Somatic Symptom Disorder". Canadian Journal of Psychiatry. 60 (4): 160–167. doi:10.1177/070674371506000402. ISSN 0706-7437. PMC 4459242. PMID 26174215.
- Treede, Rolf-Detlef; Rief, Winfried; Barke, Antonia; Aziz, Qasim; Bennett, Michael I.; Benoliel, Rafael; Cohen, Milton; Evers, Stefan; Finnerup, Nanna B.; First, Michael B.; Giamberardino, Maria Adele; Kaasa, Stein; Kosek, Eva; Lavand'homme, Patricia; Nicholas, Michael; Perrot, Serge; Scholz, Joachim; Schug, Stephan; Smith, Blair H.; Svensson, Peter; Vlaeyen, Johan W.S.; Wang, Shuu-Jiun (Jun 2015). "A classification of chronic pain for ICD-11". Pain. 156 (6): 1003–1007. doi:10.1097/j.pain.0000000000000160. ISSN 0304-3959. PMC 4450869. PMID 25844555.
- Keay, KA; Clement, CI; Bandler, R (2000). "The neuroanatomy of cardiac nociceptive pathways". In Horst, GJT. The nervous system and the heart. Totowa, New Jersey: Humana Press. p. 304. ISBN 978-0-89603-693-2.
- Coda, BA; Bonica, JJ (2001). "General considerations of acute pain". In Loeser, D; Bonica, JJ. Bonica's management of pain (3 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 978-0-443-05683-3.
- Diagnostic Methods for Neuropathic Pain: A Review of Diagnostic Accuracy Rapid Response Report: Summary with Critical Appraisal. Canadian Agency for Drugs and Technologies in Health; 2015 Apr 7. PMID 26180859
- Bogduk, N; Merskey, H (1994). Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms (second ed.). Seattle: IASP Press. p. 212. ISBN 978-0-931092-05-3.
- Paice, JA (Jul–Aug 2003). "Mechanisms and management of neuropathic pain in cancer" (PDF). Journal of Supportive Oncology. 1 (2): 107–20. PMID 15352654.
- Hansson P (1998). Nociceptive and neurogenic pain. Pharmacia & Upjon AB. pp. 52–63.
- Vadivelu N, Sinatra R (2005). "Recent advances in elucidating pain mechanisms". Current Opinion in Anesthesiology. 18 (5): 540–7. doi:10.1097/01.aco.0000183109.27297.75. PMID 16534290.
- Rusanescu G, Mao J (2014). "Notch3 is necessary for neuronal differentiation and maturation in the adult spinal cord". J Cell Mol Med. 18 (10): 2003–16. doi:10.1111/jcmm.12362. PMC 4244024. PMID 25164209.
- Geha PY, Baliki MN, Harden RN, Bauer WR, Parrish TB, Apkarian AV (2008). "The brain in chronic CRPS pain: Abnormal gray-white matter interactions in emotional and autonomic regions". Neuron. 60 (4): 570–581. doi:10.1016/j.neuron.2008.08.022. PMC 2637446. PMID 19038215.
- Baliki MN, Geha PY, Apkarian AV, Chialvo DR (2008). "Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics". J Neurosci. 28 (6): 1398–1403. doi:10.1523/JNEUROSCI.4123-07.2008. PMID 18256259.
- Tagliazucchi E, Balenzuela P, Fraiman D, Chialvo DR (2010). "Brain resting state is disrupted in chronic back pain patients". Neurosci Lett. 485 (1): 26–31. doi:10.1016/j.neulet.2010.08.053. PMC 2954131. PMID 20800649.
- May A (2009). "Chronic pain may change the structure of the brain". Pain. 137 (1): 7–15. doi:10.1016/j.pain.2008.02.034. PMID 18410991.
- Seminowicz DA, Wideman TH, Naso L, Hatami-Khoroushahi Z, Fallatah S, Ware MA, Jarzem P, Bushnell MC, Shir Y, Ouellet JA, Stone LS (2011). "Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function". Journal of Neuroscience. 31 (20): 7540–50. doi:10.1523/JNEUROSCI.5280-10.2011. PMID 21593339.
- Jensen M.P.; Sherlin L.H.; Hakiman S.; Fregni F. (2009). "Neuromodulatory approaches for chronic pain management: research findings and clinical implications". Journal of Neurotherapy. 13 (4): 196–213. doi:10.1080/10874200903334371.
- Finan, Patrick H.; Smith, Michael T. (2 February 2017). "The Comorbidity of Insomnia, Chronic Pain, and Depression: Dopamine as a Putative Mechanism". Sleep Medicine Reviews. 17 (3): 173–183. doi:10.1016/j.smrv.2012.03.003. ISSN 1087-0792. PMC 3519938. PMID 22748562.
- Ji, Ru-Rong; Berta, Temugin; Nedergaard, Maiken (2 February 2017). "Glia and pain: Is chronic pain a gliopathy?". Pain. 154 (Suppl 1): S10–S28. doi:10.1016/j.pain.2013.06.022. ISSN 0304-3959. PMC 3858488. PMID 23792284.
- Hardy, Paul A. J. (1997). Chronic pain management: the essentials. U.K.: Greenwich Medical Media. ISBN 978-1-900151-85-6.
- Main, Chris J.; Spanswick, Chris C. (2000). Pain management: an interdisciplinary approach. Churchill Livingstone. ISBN 978-0-443-05683-3.
- Thienhaus, Ole; Cole, B. Eliot (2002). "The classification of pain". In Weiner, Richard S. Pain management: A practical guide for clinicians. CRC Press. p. 29. ISBN 978-0-8493-0926-7.
- Henningsen P, Zipfel S, Herzog W (2007). "Management of functional somatic syndromes". Lancet. 369 (9565): 946–55. doi:10.1016/S0140-6736(07)60159-7. PMID 17368156.
- Stanos S, Houle TT (2006). "Multidisciplinary and interdisciplinary management of chronic pain". Physical Medicine and Rehabilitation Clinics of North America. 17 (2): 435–50, vii. doi:10.1016/j.pmr.2005.12.004. PMID 16616276.
- Chou, Roger; Huffman, LH (2 October 2007). "Medications for Acute and Chronic Low Back Pain: A Review of the Evidence for an American Pain Society/American College of Physicians Clinical Practice Guideline". Annals of Internal Medicine. 147 (7): 505–14. doi:10.7326/0003-4819-147-7-200710020-00008. PMID 17909211.
- Vardy J, Agar M (2014). "Nonopioid drugs in the treatment of cancer pain". J. Clin. Oncol. 32 (16): 1677–90. doi:10.1200/JCO.2013.52.8356. PMID 24799483.
- Elomrani F, Berrada N, L'annaz S, Ouziane I, Mrabti H, Errihani H (2015). "Pain and Cancer: A systematic review". Gulf J Oncolog. 1 (18): 32–7. PMID 26003103.
- Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ (2015). "Amitriptyline for neuropathic pain in adults". Cochrane Database Syst Rev. 7 (7): CD008242. doi:10.1002/14651858.CD008242.pub3. PMID 26146793.
- Gilron I, Baron R, Jensen T (2015). "Neuropathic pain: principles of diagnosis and treatment". Mayo Clin. Proc. 90 (4): 532–45. doi:10.1016/j.mayocp.2015.01.018. PMID 25841257.
- Ebadi, Safoora; Henschke, Nicholas; Nakhostin Ansari, Noureddin; Fallah, Ehsan; van Tulder, Maurits W (2014-03-14). "Cochrane Database of Systematic Reviews". Cochrane Database of Systematic Reviews (3): CD009169. doi:10.1002/14651858.cd009169.pub2. PMID 24627326.
- Sveinsdottir, Vigdis; Eriksen, Hege R; Reme, Silje Endresen (2012). "Assessing the role of cognitive behavioral therapy in the management of chronic nonspecific back pain". Journal of Pain Research. 5: 371–80. doi:10.2147/JPR.S25330. PMC 3474159. PMID 23091394.
- Castro, MM; Daltro, C; Kraychete, DC; Lopes, J (November 2012). "The cognitive behavioral therapy causes an improvement in quality of life in patients with chronic musculoskeletal pain". Arquivos de Neuro-Psiquiatria. 70 (11): 864–8. doi:10.1590/s0004-282x2012001100008. PMID 23175199.
- Wicksell, RK; Kemani, M; Jensen, K; Kosek, E; Kadetoff, D; Sorjonen, K; Ingvar, M; Olsson, GL (1 April 2013). "Acceptance and commitment therapy for fibromyalgia: a randomized controlled trial". European Journal of Pain. 17 (4): 599–611. doi:10.1002/j.1532-2149.2012.00224.x. PMID 23090719.
- Veehof, M. M.; Trompetter, H. R.; Bohlmeijer, E. T.; Schreurs, K. M. (2016). "Acceptance- and mindfulness-based interventions for the treatment of chronic pain: A meta-analytic review". Cognitive Behaviour Therapy. 45 (1): 5–31. doi:10.1080/16506073.2015.1098724. PMID 26818413.
- Geneen, Louise J.; Moore, R. Andrew; Clarke, Clare; Martin, Denis; Colvin, Lesley A.; Smith, Blair H. (2017-01-14). "Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews". The Cochrane Database of Systematic Reviews. 1: CD011279. doi:10.1002/14651858.CD011279.pub2. ISSN 1469-493X. PMID 28087891.
- Frank, Joseph W.; Lovejoy, Travis I.; Becker, William C.; Morasco, Benjamin J.; Koenig, Christopher J.; Hoffecker, Lilian; Dischinger, Hannah R.; Dobscha, Steven K.; Krebs, Erin E. (2017). "Patient Outcomes in Dose Reduction or Discontinuation of Long-Term Opioid Therapy". Annals of Internal Medicine. 167 (3): 181–191. doi:10.7326/m17-0598. PMID 28715848.
- Franklin, GM; American Academy of, Neurology (30 September 2014). "Opioids for chronic noncancer pain: a position paper of the American Academy of Neurology". Neurology. 83 (14): 1277–84. doi:10.1212/wnl.0000000000000839. PMID 25267983.
- Elkins, Gary; Johnson, Aimee; Fisher, William (1 April 2012). "Cognitive Hypnotherapy for Pain Management". American Journal of Clinical Hypnosis. 54 (4): 294–310. doi:10.1080/00029157.2011.654284. PMID 22655332.
- Boldt, I; Eriks-Hoogland, I; Brinkhof, M. W.; De Bie, R; Joggi, D; von Elm, E (2014). "Non-pharmacological interventions for chronic pain in people with spinal cord injury". Cochrane Database Syst Rev. 11 (11): CD009177. doi:10.1002/14651858.CD009177.pub2. PMID 25432061.
- Nugent, Shannon M.; Morasco, Benjamin J.; O'Neil, Maya E.; Freeman, Michele; Low, Allison; Kondo, Karli; Elven, Camille; Zakher, Bernadette; Motu'apuaka, Makalapua; Paynter, Robin; Kansagara, Devan (15 August 2017). "The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms". Annals of Internal Medicine. 167 (5): 319–331. doi:10.7326/M17-0155. PMID 28806817.
- Ciccone, Charles D. (2017-02-01). "Medical Marijuana: Just the Beginning of a Long, Strange Trip?". Physical Therapy. 97 (2): 239–248. doi:10.2522/ptj.20160367. ISSN 0031-9023. PMID 27660328.
- " Cannabinoids for Chronic Pain | Therapeutics Initiative". Therapeutics Initiative. 23 November 2018.
- Chen, Yi-Wen; Hunt, Michael A.; Campbell, Kristin L.; Peill, Kortni; Reid, W. Darlene (2016-04-01). "The effect of Tai Chi on four chronic conditions-cancer, osteoarthritis, heart failure and chronic obstructive pulmonary disease: a systematic review and meta-analyses". British Journal of Sports Medicine. 50 (7): 397–407. doi:10.1136/bjsports-2014-094388. ISSN 1473-0480. PMID 26383108.
- Kong, Ling Jun; Lauche, Romy; Klose, Petra; Bu, Jiang Hui; Yang, Xiao Cun; Guo, Chao Qing; Dobos, Gustav; Cheng, Ying Wu (2016-04-29). "Tai Chi for Chronic Pain Conditions: A Systematic Review and Meta-analysis of Randomized Controlled Trials". Scientific Reports. 6: 25325. doi:10.1038/srep25325. ISSN 2045-2322. PMC 4850460. PMID 27125299.
- Vickers, AJ; Vertosick, EA; Lewith, G; MacPherson, H; Foster, NE; Sherman, KJ; Irnich, D; Witt, CM; Linde, K; Acupuncture Trialists', Collaboration. (May 2018). "Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis". The Journal of Pain. 19 (5): 455–474. doi:10.1016/j.jpain.2017.11.005. PMC 5927830. PMID 29198932.
- Liu, Bu-ping; Wang, Yun-ting; Chen, Si-da (2016-12-01). "Effect of acupuncture on clinical symptoms and laboratory indicators for chronic prostatitis/chronic pelvic pain syndrome: a systematic review and meta-analysis". International Urology and Nephrology. 48 (12): 1977–1991. doi:10.1007/s11255-016-1403-z. ISSN 0301-1623. PMID 27590134.
- O'Connell, NE; Wand, BM; Marston, L; Spencer, S; DeSouza, LH (2014). "Stimulating the brain without surgery in the management of chronic pain". Cochrane Database of Systematic Reviews (4): CD008208. doi:10.1002/14651858.CD008208.pub3. PMID 24729198.
- Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D (May 2006). "Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment". Eur J Pain. 10 (4): 287–333. doi:10.1016/j.ejpain.2005.06.009. PMID 16095934.
- Singh MK, Patel J, Gallagher RM. Chronic Pain Syndrome
- Debono, DJ; Hoeksema, LJ; Hobbs, RD (August 2013). "Caring for Patients with Chronic Pain: Pearls and Pitfalls". Journal of the American Osteopathic Association. 113 (8): 620–627. doi:10.7556/jaoa.2013.023. PMID 23918913.
- Institute of Medicine of the National Academies Report (2011). Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington DC: The National Academies Press.
- A Call to Revolutionize Chronic Pain Care in America: An Opportunity in Health Care Reform. The Mayday Fund. 2009.
- Johannes C, Le T, Zhou X, Johnston J, Dworkin R (Nov 2010). "The Prevalence of Chronic Pain in United States Adults: Results of an Internet-Based Study". J Pain. 11 (11): 1230–1239. doi:10.1016/j.jpain.2010.07.002. PMID 20797916.
- Pruimboom L, van Dam AC (2007). "Chronic pain: a non-use disease". Med. Hypotheses. 68 (3): 506–11. doi:10.1016/j.mehy.2006.08.036. PMID 17071012.
- Ferini-Strambi L (2011). Sleep disorders in multiple sclerosis. Handb Clin Neurol. Handbook of Clinical Neurology. 99. pp. 1139–46. doi:10.1016/B978-0-444-52007-4.00025-4. ISBN 978-0-444-52007-4. PMID 21056246.
- Torrance N, Elliott AM, Lee AJ, Smith BH (April 2010). "Severe chronic pain is associated with increased 10 year mortality. A cohort record linkage study". European Journal of Pain. 14 (4): 380–6. doi:10.1016/j.ejpain.2009.07.006. PMID 19726210.
- McBeth J, Chiu YH, Silman AJ, et al. (2005). "Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents". Arthritis Research & Therapy. 7 (5): R992–R1000. doi:10.1186/ar1772. PMC 1257426. PMID 16207340.
- Leo, Raphael (2007). Clinical manual of pain management in psychiatry. Washington, DC: American Psychiatric Publishing. p. 58. ISBN 978-1-58562-275-7.
- Fishbain, David A.; Cole, Brandly; Cutler, R. Brian; Lewis, J.; Rosomoff, Hubert L.; Rosomoff, R. Steele (1 November 2006). "Chronic Pain and the Measurement of Personality: Do States Influence Traits?". Pain Medicine. 7 (6): 509–529. doi:10.1111/j.1526-4637.2006.00239.x. PMID 17112364.
- JESS, P.; T. JESS; H. BECK; P. BECH (1 January 1998). "Neuroticism in Relation to Recovery and Persisting Pain after Laparoscopic Cholecystectomy". Scandinavian Journal of Gastroenterology. 33 (5): 550–553. doi:10.1080/00365529850172151. PMID 9648998.
- Jess, P; Bech, P (1994). "The validity of Eysenck's neuroticism dimension within the Minnesota Multiphasic Personality Inventory in patients with duodenal ulcer. The Hvidovre Ulcer Project Group". Psychotherapy and Psychosomatics. 62 (3–4): 168–75. doi:10.1159/000288919. PMID 7846260.
- Melzack, R; Wall, PD (1996). The Challenge of Pain (2 ed.). London: Penguin. pp. 31–32. ISBN 0-14-025670-9.
- Van Damme S.; Crombez G.; Bijttebier P.; Goubert L.; Houdenhove B. V. (2001). "A confirmatory factor analysis of the Pain Catastrophizing Scale: invariant factor structure across clinical and non-clinical populations". International Association for the Study of Pain. 96 (3): 319–324. doi:10.1016/S0304-3959(01)00463-8.
- Gracely R. H. (2004). "Pain Catastrophizing and Neural Responses to Pain among Persons with Fibromyalgia". Brain. 127 (4): 835–43. doi:10.1093/brain/awh098. PMID 14960499.
- Severeijns, R; van den Hout, MA; Vlaeyen, JW (June 2005). "The causal status of pain catastrophizing: an experimental test with healthy participants". European Journal of Pain. 9 (3): 257–65. doi:10.1016/j.ejpain.2004.07.005. PMID 15862475.
- Molton, I. R.; Terrill, A. L. (2014). "Overview of persistent pain in older adults". American Psychologist. 69 (2): 197–207. doi:10.1037/a0035794. PMID 24547805.
- Zaza, C.; Baine, N. (2002). "Cancer pain and psychological factors: A critical review of the literature". Journal of Pain and Symptom Management. 24 (5): 526–542. doi:10.1016/s0885-3924(02)00497-9.
- Kreitler S; Niv D (2007). "Cognitive impairment in chronic pain" (pdf). Pain: Clinical Updates. XV (4): 1–4. Retrieved 2008-04-15.