Abstract
It was not until the twentieth century that pain was considered a disease. Before
that it was managed medically as a symptom. The motivations for declaring chronic
pain a disease, whether of the body or of the brain, include increasing its legitimacy
as clinical problem and research focus worthy of attention from healthcare and research
organizations alike. But 1 problem with disease concepts is that having a disease
favors medical solutions and tends to reduce patient participation. We argue that
chronic pain, particularly chronic primary pain (recently designated a first tier
pain diagnosis in International Diagnostic Codes 11), is a learned state that is not
intransigent even if it has biological correlates. Chronic pain is sometimes a symptom,
and may sometimes be its own disease. But here we question the value of a disease
focus for much of chronic pain for which patient involvement is essential, and which
may need a much broader societal approach than is suggested by the disease designation.
Perspective
This article examines whether designating chronic pain a disease of the body or brain
is helpful or harmful to patients. Can the disease designation help advance treatment,
and is it needed to achieve future therapeutic breakthrough? Or does it make patients
over-reliant on medical intervention and reduce their engagement in the process of
recovery?
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of PainAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Brain mechanisms of the placebo effect: An affective appraisal account.Annu Rev Clin Psychol. 2017; 13: 73-98https://doi.org/10.1146/annurev-clinpsy-021815-093015
- Effect of pain reprocessing therapy vs placebo and usual care for patients with chronic back pain: A randomized clinical trial.JAMA psychiatry. 2022; 79: 13-23https://doi.org/10.1001/jamapsychiatry.2021.2669
- Endogenous opioid peptides in the descending pain modulatory circuit.Neuropharmacology. 2020; 15: 108-131https://doi.org/10.1016/j.neuropharm.2020.108131
- Nociception, pain, negative moods, and behavior selection.Neuron. 2015; 87: 474-491https://doi.org/10.1016/j.neuron.2015.06.005
- Allostasis theory in opioid tolerance.Pain. 2020; https://doi.org/10.1097/j.pain.0000000000002280
- Refractory dependence on opioid analgesics.Pain. 2019; 160: 2655-2660https://doi.org/10.1097/j.pain.0000000000001680
- Increased stress and effectiveness of placebos and “active” drugs.Science. 1960; 132 (Available at:): 91-92https://www.ncbi.nlm.nih.gov/pubmed/13798214Date accessed: March 31, 2022
- Anesthesiology in the People's Republic of China.Anesthesiology. 1974; 40: 175-186https://doi.org/10.1097/00000542-197402000-00016
- Opioidergic tone and pain susceptibility: Interactions between reward systems and opioid receptors.Pain. 2017; 158: 185-186https://doi.org/10.1097/j.pain.0000000000000726
- Pain and analgesia: The value of salience circuits.Prog Neurobiol. 2013; 104: 93-105https://doi.org/10.1016/j.pneurobio.2013.02.003
- Trends in funding for research on pain: A report on the National Institutes Of Health grant awards over the years 2003 to 2007.J Pain. 2008; 9: 1077-1087https://doi.org/10.1016/j.jpain.2008.09.008
- Clinical, educational, and epidemiological value of autopsy.Lancet. 2007; 369 (Available at:): 1471-1480
- Migraine and reward system-or is it aversive?.Curr Pain Headache Rep. 2014; 18: 410https://doi.org/10.1007/s11916-014-0410-y
- Deaths of despair and the future of capitalism.Princeton University Press, 2020 (ISBN: 9780691190785)
- Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century.Proc Natl Acad Sci U S A. 2015; 112: 15078-15083https://doi.org/10.1073/pnas.1518393112
- An endogenous opioid circuit determines state-dependent reward consumption.Nature. 2021; 598: 646-651https://doi.org/10.1038/s41586-021-04013-0
- Social stress engages opioid regulation of locus coeruleus norepinephrine neurons and induces a state of cellular and physical opiate dependence.Neuropsychopharmacology. 2013; 38: 1833-1843https://doi.org/10.1038/npp.2013.117
- Fibromyalgia: A clinical review.Jama. 2014; 311: 1547-1555https://doi.org/10.1001/jama.2014.3266
- Normalizing fibromyalgia as a chronic illness.Postgrad Med. 2018; 130: 9-18https://doi.org/10.1080/00325481.2018.1411743
- Reframing chronic pain as a disease, not a symptom: Rationale and implications for pain management.Postgrad Med. 2019; 131: 185-198https://doi.org/10.1080/00325481.2019.1574403
- Cross-species affective functions of the medial forebrain bundle-implications for the treatment of affective pain and depression in humans.Neurosci Biobehav Rev. 2011; 35: 1971-1981https://doi.org/10.1016/j.neubiorev.2010.12.009
- Tobacco product use and cessation indicators among adults — United States, 2018.MMWR Morb Mortal Wkly Rep. 2019; 68
- The pain switch: An "ouch" detector.Pain. 2015; 156: 2164-2166https://doi.org/10.1097/j.pain.0000000000000303
- Patients are socially excluded when their pain has no medical explanation.J Pain. 2016; 17: 1028-1035https://doi.org/10.1016/j.jpain.2016.06.005
- Neuroinflammation: The devil is in the details.J Neurochem. 2016; 139: 136-153https://doi.org/10.1111/jnc.13607
- Functional neurological disorder: Lighting the way to a new paradigm for medicine.Brain. 2021; 144: 3279-3282https://doi.org/10.1093/brain/awab358
- Pain and the PAG: Learning from painful mistakes.Nat Neurosci. 2014; 17: 1438-1439https://doi.org/10.1038/nn.3844
- Does rejection hurt? An FMRI study of social exclusion.Science. 2003; 302 (Available at:): 290-292
- Common brain mechanisms of chronic pain and addiction.Neuron. 2016; 89: 11-36https://doi.org/10.1016/j.neuron.2015.11.027
- Reduction of skin innervation is associated with a severe fibromyalgia phenotype.Ann Neurol. 2019; 86: 504-516https://doi.org/10.1002/ana.25565
- Comorbid posttraumatic stress disorder and opiate addiction: A literature review.J Addict Dis. 2013; 32: 168-179https://doi.org/10.1080/10550887.2013.795467
- Understanding how opioids contribute to reward and analgesia.Reg Anesth Pain Med. 2007; 32: 242-246https://doi.org/10.1016/j.rapm.2007.01.001
- It’s misleading to call addiction a disease.https://www.nytimes.com/2022/01/15/opinion/addiction-disease.html. New York Times, 2022 (Available at:)
- Nociplastic pain: Towards an understanding of prevalent pain conditions.Lancet. 2021; 397: 2098-2110https://doi.org/10.1016/S0140-6736(21)00392-5
- Analgesic drug therapy in cancer pain: Principles and practice.Med Clin North Am. 1987; 71: 207-232https://doi.org/10.1016/s0025-7125(16)30866-5
- The Birth of the Clinic: An Archeology of Medical Perception.Vintage Books, New York, NY1973
- Interdisciplinary chronic pain management: Past, present, and future.Am Psychol. 2014; 69: 119-130https://doi.org/10.1037/a0035514
- Glial cells and chronic pain.Neuroscientist. 2010; 16: 519-531https://doi.org/10.1177/1073858409360822
- Neuroimaging of fibromyalgia.Best Pract Res Clin Rheumatol. 2011; 25: 271-284https://doi.org/10.1016/j.berh.2011.02.003
- A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia etiopathogenesis.Semin Arthritis Rheum. 2019; 48: 933-940https://doi.org/10.1016/j.semarthrit.2018.08.003
- Experimental evidence on the nature of cutaneous hyperalgesia.J Clin Invest. 1950; 29: 115-140https://doi.org/10.1172/JCI102227
- Shape shifting pain: Chronification of back pain shifts brain representation from nociceptive to emotional circuits.Brain. 2013; 136: 2751-2768https://doi.org/10.1093/brain/awt211
- Identification of two related pentapeptides from the brain with potent opiate agonist activity.Nature. 1975; 258: 577-580
- From the neuromatrix to the pain matrix (and back).Exp Brain Res. 2010; 205: 1-12https://doi.org/10.1007/s00221-010-2340-1
IASP. Available at: https://wwwiasp-painorg/resources/terminology/#central-sensitization Accessed December 9, 2021.
- Childhood adversities in patients with fibromyalgia and somatoform pain disorder.Eur J Pain. 2003; 7: 113-119https://doi.org/10.1016/S1090-3801(02)00072-1
- Managing somatization: Medically unexplained should not mean medically ignored.J Gen Intern Med. 2006; 21 (Available at): 797-799
- Substance use disorders in patients with posttraumatic stress disorder: A review of the literature.Am J Psychiatry. 2001; 158: 1184-1190https://doi.org/10.1176/appi.ajp.158.8.1184
- Glia and pain: Is chronic pain a gliopathy?.Pain. 2013; 154: S10-S28https://doi.org/10.1016/j.pain.2013.06.022
- Neuroinflammation and central sensitization in chronic and widespread pain.Anesthesiology. 2018; 129: 343-366https://doi.org/10.1097/ALN.0000000000002130
- Placebos in chronic pain: Evidence, theory, ethics, and use in clinical practice.BMJ. 2020; 370: m1668https://doi.org/10.1136/bmj.m1668
- Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety.Arch Gen Psychiatry. 2003; 60: 789-796https://doi.org/10.1001/archpsyc.60.8.789
- Rehabilitation in multiple sclerosis: A systematic review of systematic reviews.Arch Phys Med Rehabil. 2017; 98: 353-367https://doi.org/10.1016/j.apmr.2016.04.016
- Evidence for a large-scale brain system supporting allostasis and interoception in humans.Nat Hum Behav. 2017; 1https://doi.org/10.1038/s41562-017-0069
- Patients presenting with somatic complaints: Epidemiology, psychiatric comorbidity and management.Int J Methods Psychiatr Res. 2003; 12: 34-43
- The neural code for pain: From single-cell electrophysiology to the dynamic pain connectome.Neuroscientist. 2016; 23: 397-414https://doi.org/10.1177/1073858416667716
- Brain signature and functional impact of centralized pain: A multidisciplinary approach to the study of chronic pelvic pain (MAPP) network study.Pain. 2017; https://doi.org/10.1097/j.pain.0000000000001001
- Somatoform pain: A developmental theory and translational research review.Psychosom Med. 2012; 74: 717-727https://doi.org/10.1097/PSY.0b013e3182688e8b
- Central sensitization: A generator of pain hypersensitivity by central neural plasticity.J Pain. 2009; 10: 895-926https://doi.org/10.1016/j.jpain.2009.06.012
- The effect of systemic morphine upon diffuse noxious inhibitory controls (DNIC) in the rat: Evidence for a lifting of certain descending inhibitory controls of dorsal horn convergent neurones.Brain Res. 1981; 215: 257-274https://doi.org/10.1016/0006-8993(81)90506-0
- The pain matrix reloaded: A salience detection system for the body.Prog Neurobiol. 2011; 93: 111-124https://doi.org/10.1016/j.pneurobio.2010.10.005
- Brain change in addiction as learning, not disease.N Engl J Med. 2018; 379: 1551-1560https://doi.org/10.1056/NEJMra1602872
- Evidence for brain glial activation in chronic pain patients.Brain. 2015; 138: 604-615https://doi.org/10.1093/brain/awu377
- Probability and predictors of remission from life-time nicotine, alcohol, cannabis or cocaine dependence: Results from the national epidemiologic survey on alcohol and related conditions.Addiction. 2011; 106: 657-669
- The natural history of chronic pain in the community: A better prognosis than in the clinic?.J Rheumatol. 1996; 23: 1617-1620
- Medically unexplained symptoms: Are we making progress?.Br J Gen Pract. 2019; 69: 164-165https://doi.org/10.3399/bjgp19X701885
- (323) Kappa opioid receptors in the nucleus accumbens mediate pain-induced decrease in motivated behavior.J Pain. 2016; 17: S56https://doi.org/10.1016/j.jpain.2016.01.230
- Allostasis and allostatic load: Implications for neuropsychopharmacology.Neuropsychopharmacology. 2000; 22: 108-124https://doi.org/10.1016/S0893-133X(99)00129-3
- Current challenges in glia-pain biology.Neuron. 2009; 64: 46-54https://doi.org/10.1016/j.neuron.2009.09.033
- Pain mechanisms: A new theory.Science. 1965; 150 (Available at:): 971-979
- IL-8 and IL-6 primarily mediate the inflammatory response in fibromyalgia patients.J Neuroimmunol. 2016; 290: 22-25https://doi.org/10.1016/j.jneuroim.2015.11.011
- Fear in the context of pain: Lessons learned from 100 years of fear conditioning research.Behav Res Ther. 2020; 131103635https://doi.org/10.1016/j.brat.2020.103635
- MRI scans offer new tools for autopsy.Jama. 2007; 298 (Available at:): 392-393
- Non-cardiac chest pain: Prognosis and secondary healthcare utilisation.Open Heart. 2018; 5e000859https://doi.org/10.1136/openhrt-2018-000859
- Fifteen years of explaining pain: The past, present, and future.J Pain. 2015; 16: 807-813https://doi.org/10.1016/j.jpain.2015.05.005
- What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of 'centralized' pain?.Arthritis Res Ther. 2014; 16: 425https://doi.org/10.1186/s13075-014-0425-0
- Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain.Pain. 2018; 159: 919-928https://doi.org/10.1097/j.pain.0000000000001167
- Brain circuits encoding reward from pain relief.Trends Neurosci. 2015; 38: 741-750https://doi.org/10.1016/j.tins.2015.09.003
- Selective modulation of tonic aversive qualities of neuropathic pain by morphine in the central nucleus of the amygdala requires endogenous opioid signaling in the anterior cingulate cortex.Pain. 2020; 161: 609-618https://doi.org/10.1097/j.pain.0000000000001748
- Amygdala, neuropeptides, and chronic pain-related affective behaviors.Neuropharmacology. 2020; 170108052https://doi.org/10.1016/j.neuropharm.2020.108052
- Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain.2021
- Pain ITftCoC. The IASP classification of chronic pain for ICD-11: Chronic primary pain.Pain. 2019; 160: 28-37https://doi.org/10.1097/j.pain.0000000000001390
- The biology of social attachments: Opiates alleviate separation distress.Biol Psychiatry. 1978; 13: 607-618
- Variation in the beta-endorphin, oxytocin, and dopamine receptor genes is associated with different dimensions of human sociality.Proc Natl Acad Sci U S A. 2017; 114: 5300-5305https://doi.org/10.1073/pnas.1700712114
- Opiate receptor: Demonstration in nervous tissue.Science. 1973; 179: 1011-1014
- Introduction for the allostatic load special issue.Physiol Behav. 2012; 106: 1-4https://doi.org/10.1016/j.physbeh.2011.12.019
- Functional imaging of brain responses to pain. A review and meta-analysis (2000).Neurophysiol Clin. 2000; 30 (Available at:): 263-288
- Reward, motivation, and emotion of pain and its relief.Pain. 2017; 158: S43-S49https://doi.org/10.1097/j.pain.0000000000000798
- Civilization, and the State: A History of Public Health from Ancient to Modern Times.Routledge, New York, NY1999
- The Greatest Benefit to Mankind: A Medical History of Humanity (The Norton History of Science).W. W. Norton, New York1999
- Drug-induced regulatory overcompensation has motivational consequences: Implications for homeostatic and allostatic models of drug addiction.Temperature (Austin). 2014; 1: 248-256https://doi.org/10.4161/23328940.2014.944802
- Interactions between the immune and nervous systems in pain.Nat Med. 2010; 16: 1267-1276https://doi.org/10.1038/nm.2234
- The power of the visible: The meaning of diagnostic tests in chronic back pain.Soc Sci Med. 1999; 48 (Available at:): 1189-1203
- Interface of physical and emotional stress regulation through the endogenous opioid system and mu-opioid receptors.Progress Neuro-Psychopharmacol Biolog Psychiat. 2005; 29: 1264-1280https://doi.org/10.1016/j.pnpbp.2005.08.011
- Fibromyalgia outcomes over time: Results from a prospective observational study in the United States.Open Rheumatol J. 2016; 30: 109-121https://doi.org/10.2174/1874312901610010109
- Endogenous opioidergic dysregulation of pain in fibromyalgia: A PET and fMRI study.Pain. 2016; 157: 2217-2225https://doi.org/10.1097/j.pain.0000000000000633
- Social allostasis: Anticipatory regulation of the internal milieu.Front Evol Neurosci. 2011; 2: 111https://doi.org/10.3389/fnevo.2010.00111
- What is a disease?.EMBO Rep. 2004; 5: 650-653https://doi.org/10.1038/sj.embor.7400195
- Pain: A precision signal for reinforcement learning and control.Neuron. 2019; 101: 1029-1041https://doi.org/10.1016/j.neuron.2019.01.055
- Cytokine biomarkers and chronic pain: Association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness.Pain. 2011; 152: 2802-2812https://doi.org/10.1016/j.pain.2011.09.005
- Neurobiology of fibromyalgia and chronic widespread pain.Neuroscience. 2016; 338: 114-129https://doi.org/10.1016/j.neuroscience.2016.06.006
- Fibromyalgia: An afferent processing disorder leading to a complex pain generalized syndrome.Pain Physician. 2011; 14 (Available at:): E217-E245
- Analgesic and anti-hyperalgesic effects of muscle injections with lidocaine or saline in patients with fibromyalgia syndrome.Eur J Pain. 2014; 18: 803-812https://doi.org/10.1002/j.1532-2149.2013.00422.x
- Allostasis: A new paradigm to explain arousal pathology.in: Fisher S Reason J Handbook of Life Stress. Cognition and Health John Wiley, Chichester1988: 629-649
- Unique cytokine signature in the plasma of patients with fibromyalgia.J Immunol Res. 2014; 2014938576https://doi.org/10.1155/2014/938576
- Psychogenic pain: Old and new.in: Corns J Routledge Handbook on the Philosophy of Pain. Routledge, London2017
- The right to pain relief: Its origins in end-of-life care and extension to chronic pain care.Clin J Pain. 2021; 38: 58-63
- Patient action: As means and end for chronic pain care.Pain. 2017; 158: 1405-1407https://doi.org/10.1097/j.pain.0000000000000921
- Mesolimbic dopamine signaling in acute and chronic pain: Implications for motivation, analgesia, and addiction.Pain. 2016; 157: 1194-1198https://doi.org/10.1097/j.pain.0000000000000494
- Getting the pain you expect: Mechanisms of placebo, nocebo and reappraisal effects in humans.Nat Med. 2010; 16: 1277-1283https://doi.org/10.1038/nm.2229
- A vulnerability to chronic pain and its interrelationship with resistance to analgesia.Brain. 2016; 139: 1869-1872https://doi.org/10.1093/brain/aww147
- How neuroimaging studies have challenged us to rethink: Is chronic pain a disease?.J Pain. 2009; 10: 1113-1120https://doi.org/10.1016/j.jpain.2009.09.001
- Chronic pain as a symptom or a disease: The IASP classification of chronic pain for the international classification of diseases (ICD-11).Pain. 2019; 160: 19-27https://doi.org/10.1097/j.pain.0000000000001384
- New concepts of pain.Best Pract Res Clin Rheumatol. 2019; 33101415https://doi.org/10.1016/j.berh.2019.04.007
- Neuropathic pain and spinal microglia: A big problem from molecules in "small" glia.Trends Neurosci. 2005; 28: 101-107https://doi.org/10.1016/j.tins.2004.12.002
- Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain.Clin J Pain. 2002; 18: 355-365
- Small fibre pathology in patients with fibromyalgia syndrome.Brain. 2013; 136: 1857-1867https://doi.org/10.1093/brain/awt053
- Endogenous opioids: The downside of opposing stress.Neurobiol Stress. 2015; 1: 23-32https://doi.org/10.1016/j.ynstr.2014.09.006
- What is the evidence for physical therapy poststroke? A systematic review and meta-analysis.PLoS One. 2014; 9: e87987https://doi.org/10.1371/journal.pone.0087987
- Neuropathic pain and symptoms of potential small-fiber neuropathy in fibromyalgic patients: A national on-line survey.Joint Bone Spine. 2021; 88105153https://doi.org/10.1016/j.jbspin.2021.105153
- Neural correlates of social exclusion across ages: A coordinate-based meta-analysis of functional MRI studies.Neuroimage. 2017; 153: 359-368https://doi.org/10.1016/j.neuroimage.2017.02.050
- Behavioral conceptualization and treatment of chronic pain.Annu Rev Clin Psychol. 2020; 16: 187-212https://doi.org/10.1146/annurev-clinpsy-050718-095744
- An fMRI-based neurologic signature of physical pain.N Engl J Med. 2013; 368: 1388-1397https://doi.org/10.1056/NEJMoa1204471
- Placebo effects on human mu-opioid activity during pain.Proc Natl Acad Sci U S A. 2007; 104: 11056-11061https://doi.org/10.1073/pnas.0702413104
- Glial activation: A driving force for pathological pain.Trends Neurosci. 2001; 24: 450-455https://doi.org/10.1016/s0166-2236(00)01854-3
- It is hard work behaving as a credible patient: Encounters between women with chronic pain and their doctors.Soc Sci Med. 2003; 57 (Available at:): 1409-1419
- Pleasure into pain: The consequences of long-term opioid use.Addict Behav. 2004; 29: 1311-1324https://doi.org/10.1016/j.addbeh.2004.06.007
- Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome.World J Gastroenterol. 2007; 13: 3699-3704https://doi.org/10.3748/wjg.v13.i27.3699
- The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.Arthritis Care Res (Hoboken). 2010; 62: 600-610https://doi.org/10.1002/acr.20140
- Role of central dopamine in pain and analgesia.Expert Rev Neurother. 2008; 8: 781-797https://doi.org/10.1586/14737175.8.5.781
- Evidence for a central component of postinjury pain hypersensitivity.Nature. 1983; 308: 686-688
- Central sensitization: Implications for the diagnosis and treatment of pain.Pain. 2011; 152: S2-15https://doi.org/10.1016/j.pain.2010.09.030
- What to call the amplification of nociceptive signals in the central nervous system that contribute to widespread pain?.Pain. 2014; 155: 1911-1912https://doi.org/10.1016/j.pain.2014.07.021
- Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): Its relevance for acute and chronic pain states.Curr Opin Anaesthesiol. 2010; 23: 611-615https://doi.org/10.1097/ACO.0b013e32833c348b
- Editorial review: An update on central sensitivity syndromes and the issues of nosology and psychobiology.Curr Rheumatol Rev. 2015; 11: 70-85https://doi.org/10.2174/157339711102150702112236
- Regional mu opioid receptor regulation of sensory and affective dimensions of pain.Science. 2001; 293: 311-315https://doi.org/10.1126/science.1060952
- Neurobiological mechanisms of placebo responses.Ann N Y Acad Sci. 2009; 1156: 198-210https://doi.org/10.1111/j.1749-6632.2009.04424.x
Article info
Publication history
Published online: May 13, 2022
Footnotes
Conflicts of interest: Dr Ballantyne reports personal fees from Motley Rice LLP, personal fees from Nix Patterson LLP, outside the submitted work; and President, Physicians for Responsible Opioid Prescribing (PROP), a voluntary unpaid position in a 501c3 charitable organization . PROP advocates for rational opioid prescribing.
Identification
Copyright
© 2022 by United States Association for the Study of Pain, Inc.
