Chronic Pain

Chronic pain is pain that continues or returns for longer than about three months, and it often outlasts the tissue injury or illness that first caused it. The pain entry defines the sensation as an unpleasant sensory and emotional experience, and chronic pain differs from acute pain in its duration and, usually, in its function: acute pain warns of threat, while persistent pain no longer serves that protective role. Because it affects an estimated one in five people worldwide, it is one of the most common long-term health problems, and it can become the main clinical concern for a patient. It is now classified in the ICD-11 system as a condition in its own right in some forms, not only as a symptom.

Chronic pain is multifactorial. Its biological side involves changes in peripheral nerves, the central nervous system and the immune system. Its psychological and social side involves mood, coping, work, income and access to care, which is why the condition is usually approached through a biopsychosocial framework. These factors interact: pain can drive depression and disability, and those same conditions can amplify pain. The entry therefore links basic mechanisms to clinical syndromes, assessment, treatment, health policy and the conceptual debates that continue to shape the field.

The article begins with definitions, classification and epidemiology, then examines the mechanisms of pain persistence in the nervous and immune systems and the psychological and social factors that influence it. It describes the major clinical syndromes, the methods used to assess and diagnose the condition, and the multimodal approaches used in its management. It closes with public health and access issues, the history of conceptual change, and unresolved questions about definitions, sex differences and treatment effectiveness.

Definition and classification

The International Association for the Study of Pain (IASP) defines chronic pain as pain that persists or recurs for longer than three months. The threshold is a convention rather than a biological boundary. The IASP task force that developed the ICD-11 classification acknowledged that the minimum duration is arbitrary, though it is consistent with the time cutoffs used for other chronic conditions and in many clinical trials and health statistics. In the absence of objective markers that separate an acute phase of pain from a chronic one, a fixed interval allows researchers and clinicians to compare populations and to decide when a pain problem needs its own diagnostic evaluation and treatment. Earlier conventions, used in some clinical traditions and research, placed the threshold at six months. The shorter three-month criterion was adopted because it captures the point at which pain usually outlasts normal tissue healing and begins to function as a problem in its own right rather than as a warning signal.

Acute pain is generally understood as a protective response that signals actual or threatened tissue damage and usually resolves as the injury heals. Chronic pain differs in that its warning function has lost much of its relevance: the pain persists after healing should have been complete, or it recurs without a clear ongoing injury. The transition is not a single event. Many people with acute pain recover, but a minority continue to experience pain as the nervous system adapts to ongoing input, and psychological and social factors shape whether pain resolves or persists. The clinical concern is that pain which has lasted a few weeks may already be establishing the changes that sustain it, which is why early monitoring is emphasised in later sections of this entry.

The International Classification of Diseases, 11th Revision (ICD-11), adopted by the World Health Organization in 2019, contains a chronic pain chapter for the first time. Its central division separates chronic primary pain from chronic secondary pain. Chronic primary pain, coded MG30.0, is pain in one or more anatomical regions that lasts or recurs beyond three months, is associated with significant emotional distress or functional disability, and cannot be better explained by another chronic pain condition. Chronic secondary pain is pain that accompanies an identifiable underlying disease or condition, such as cancer, surgery or trauma, nerve lesions, or certain headache and visceral disorders. Within this framework, chronic primary pain is recognised as a condition in its own right, even when its etiology remains unknown, while chronic secondary pain is treated as a symptom of another disease that often requires interdisciplinary care. This structure has been described as bringing the International Classification of Diseases into line with a biopsychosocial understanding of pain, and field testing reported that the new codes were less ambiguous than earlier versions.

Duration-based definitions have drawn criticism on several grounds. Three months is a poor fit for some age groups: for young children, a three-month period represents a much larger share of life, while for older adults recovery from injury or surgery may be slower, so the same interval can mean different things clinically. Some conditions, such as trigeminal neuralgia or pain from diabetic polyneuropathy, have characteristic features that justify diagnosis before the threshold is reached. Critics also note that a time threshold says nothing about pain mechanism, severity or impact, and that it has been used inconsistently across studies, which complicates comparison. These concerns have fed into the broader debate, explored elsewhere in this entry, about whether chronic pain is best understood as a disease or as a symptom of other conditions.

Epidemiology and burden

Estimates of how many people live with chronic pain cluster around one adult in five, but the spread between studies is wide. The figure most often repeated is that these conditions affect patients, their families and society at large, impacting 20% of the global population. A 2025 meta-analysis of general-population studies covering adults aged 18 to 95 reported a pooled prevalence of 26.99%, while a review limited to chronic widespread pain returned a much lower global CWP prevalence estimate of 9.6%. Definitions explain part of the gap. The US National Health Interview Survey counts chronic pain as pain on most days or every day during the previous 3 months, whereas a 2010 US internet survey used a six-month threshold and found a weighted point-prevalence of chronic pain ... 30.7%. Country comparisons also vary. In European national surveys, the reported prevalence was 10%, 10%, 11%, 13%, and 23% in France, Italy, Germany, Portugal, and Spain, respectively. The 2025 meta-analysis found no geographical difference in its pooled estimate, whereas a separate review found that HDI was noted to be the socioeconomic factor related to CWP prevalence. Data from children show a similar split: a pooled estimate for low- and middle-income countries was 8% chronic pain, compared with the 20% to 35% estimated in high-income countries from individual studies.

Sex differences are consistent in most datasets but not uniform in size. In the 2025 meta-analysis, women were estimated at 31.42% against 21.63% for men, although that difference did not reach statistical significance. US national data for 2019 showed 21.7% of women and 19.0% of men with chronic pain. A study of older adults in São Paulo found chronic pain was more frequent in females (27.2%) than in males (14.5%), and a US study of older adults found no statistically significant differences in chronic pain status based on age, gender, marital status, level of education, or location of residence.

Prevalence rises with age in most studies, though the pattern flattens at older ages in some. In the 2010 internet survey, the prevalence of chronic pain increased with advancing age up through the age of 64 years, and then leveled off. A Spanish study reported rates from 18-29 y: 20.13% ... to 65+ years: 41.75%. Among US older adults, the prevalence of chronic pain among adults aged 65 to 84 was 38% and the prevalence of chronic pain among adults aged 85 and older was 43%.

Socioeconomic position is linked to higher prevalence. Lower-income countries show higher rates, as noted above, and within countries the pattern holds: the prevalence of chronic pain is lower among older adults with higher income. In the São Paulo study, among males, only the individual aspects were significant for the occurrence of chronic pain, such as low educational attainment (OR = 1.88) and insufficient income (OR = 1.63), while among women unfavorable living conditions (OR = 1.59) ... were most likely to have chronic pain. The authors attributed the larger gap for women to structural factors inherent in a highly unequal society.

Pain is also common within chronic diseases. In cancer, a review reported that the overall prevalence of cancer-related pain was reported to be 44.5%, and in metastatic, advanced, and terminal patients, reaching 54.6%; at least half of cancer patients experience pain at least three months after therapy. An umbrella review also found high pain prevalence in heart, liver, and kidney failure; COPD; multiple sclerosis; Huntington's disease; Parkinson's disease; Alzheimer's disease; traumatic brain injury; and cancer. For heart failure, the prevalence of pain in 20,875 patients with CHF varied from 23 to 85%. In kidney disease, across the studies reporting overall pain in patients on HD, the estimated pooled prevalence was 60.5%. In liver disease, a US national cohort found that participants with liver disease were more likely to report pain than those without liver disease (42% vs. 22%). The umbrella review concluded that the prevalence of pain in chronic diseases is high, in some cases even higher than the cardinal symptoms of these diseases/conditions, and that pain in chronic diseases does not receive enough attention and is not properly managed. Pain frequently accompanies mental disorders as well, a relationship treated in the psychological and social factors section.

The burden extends beyond the pain itself. A narrower category, high-impact chronic pain, is defined as pain that also limited daily life or work activities on most days or every day during the previous 3 months. In the US, the prevalence of high-impact chronic pain was 7.4% (or 36.4% of adults who had chronic pain). Quality of life is also affected: in cancer populations, a significant negative correlation between quality of life and pain variables, including pain intensity, pain distress, and pain interference has been reported. Among older adults, chronic pain is associated with cognitive decline, dementia, and the risk of premature death. Chronic non-cancer pain is described as highly debilitating and have high cost implications to health and social care, although the sources consulted for this section gave few quantified figures on employment loss or treatment spending.

Biological mechanisms of persistence

Pain research now sorts pain by mechanism. The IASP recognises three mechanistic descriptors: nociceptive, neuropathic and nociplastic pain. These describe broad processes that may contribute to pain, so they are not diagnoses and do not confirm that a specific mechanism has been measured in an individual patient. They are often called mechanistic descriptors because they describe broad processes thought to contribute to pain. They are not diagnoses, and using a descriptor does not mean that a specific biological mechanism has been directly measured or confirmed in an individual.

Three mechanistic categories

Nociceptive pain is the signal produced when tissue outside the nervous system is actually or potentially harmed, which activates nociceptors. Neuropathic pain has a different origin: it follows injury or disease of the somatosensory system, and it may arise in peripheral nerves, as in diabetic polyneuropathy or postherpetic neuralgia, or in the central nervous system, as in central post-stroke pain (IASP defines neuropathic pain as pain caused by a lesion or disease of the somatosensory nervous system. It may be peripheral, as in painful diabetic polyneuropathy or postherpetic neuralgia, or central, as in central post-stroke pain.).

Nociplastic pain is the least intuitive category. It is pain that arises from altered nociception even though there is no clear evidence of tissue damage or of a lesion in the somatosensory system (It is defined as "pain that arises from altered nociception" not fully explained by nociceptive or neuropathic pain mechanisms.). The concept was adopted in 2017, after clinicians had long noted patients whose pain fitted neither older category (Terms such as 'idiopathic pain', functional pain', 'centralized pain', 'central sensitization', and 'central hypersensitivity' had been proposed, when in 2017, the IASP Council adopted the term "nociplastic pain" as a third mechanistic descriptor of chronic pain.). Its mechanisms are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles. Fibromyalgia is the typical example. The categories also overlap in practice: distinguishing between NpP and NeP can be particularly challenging, since they share many clinical characteristics, including pain hypersensitivity and spontaneous pain. Diagnostic tools for nociplastic pain remain under debate, and some authors argue that the category should be merged into neuropathic pain (Integrating nociplastic pain into neuropathic pain framework), a proposal that has not been widely adopted.

Peripheral and central sensitization

Sensitization describes how persistent input can make the pain system more responsive over time. Peripheral sensitization is described as the hyperexcitability of peripheral nociceptors and is considered largely due to the effects of neurotrophins and pro-inflammatory molecules in promoting nociceptor depolarization. Central sensitization occurs in the spinal cord. Peripheral sensitization leads to increased action potential firing and transmitter release in the dorsal horn of the spinal cord, where somatosensory information is processed. Dorsal horn neurons react to the rising input with heightened excitability, a process termed central sensitization. The process depends on NMDA-type glutamate receptors: enhanced depolarization leads to the recruitment of N-methyl-D-aspartate (NMDA)-type glutamate receptors. NMDA and neuropeptide receptor activation produces a sharp increase in intracellular calcium, triggering signaling pathways and gene expression changes that promote a long-term shift in the activity of nociceptive circuits. Some researchers compare this to long-term potentiation of excitatory transmission in the hippocampus. The clinical result is an exaggerated response to painful stimuli (hyperalgesia) and contributes to pain elicited by normally nonpainful stimuli (allodynia). Affected neurons may also show spontaneous autonomous activity, lower thresholds for activation or pain, and wider receptive fields.

Central sensitization is not established as the single cause of chronic pain. One critical review states that it is not demonstrated that Central Sensitization causes Chronic Pain.

Immune contributions and sex differences

Glial cells and immune signalling are central to this picture. Microglia, the resident immune cells of the central nervous system, have been implicated in neuropathic pain: dysregulation of microglia has been critically implicated in the genesis of neuropathic pain. Much of the early evidence came from male rodents, and elucidating this microglia-neuronal signalling pathway was based on studies using only male rodents. Recent evidence has shown that the role of microglia in pain is sexually dimorphic. In one nerve-injury model, the expression of the gene encoding the purinergic receptor P2X4R in microglia, previously shown to mediate neuropathic pain in male mice, was increased after nerve injury in male but not female mice. In females, adaptive immune cells, possibly T cells, may mediate pain hypersensitivity. Following peripheral nerve injury, females demonstrated substantially greater infiltration of T cells into both sciatic nerves and spinal cord compared to males, accompanied by distinct cytokine and chemokine profiles that favor adaptive immune cell recruitment. Sex hormones probably contribute: sex steroids have profound influences on immune functioning and may be responsible for many sex differences in pain. Proposed mechanisms remain preclinical. One pathway analysis suggests that females may preferentially use Th1 and males Th2 T cell activity to mediate chronic pain. Human data show that glial reactivity is observed in patients of both sexes, so the sex-specific picture is not yet fully translated to clinical practice.

Genetic risk and gene expression

Genetic factors influence who develops persistent pain, but the evidence is less specific than for the sensitization pathways above. Family and twin research points to a heritable component, and genome-wide studies have linked many variants to pain-related traits, usually with small individual effects. The clearest single-gene examples come from rare disorders: gain-of-function variants in the sodium channel gene SCN9A cause inherited erythromelalgia, while loss-of-function variants cause congenital insensitivity to pain. Gene expression also changes after nerve injury and inflammation in sensory neurons and spinal cord, which links the molecular changes described above to persistence, as the P2X4R findings illustrate. Studies of common variants in candidate genes have produced inconsistent results, which limits their use in individual risk prediction.

Nervous system changes and brain involvement

Modulation in the spinal cord and descending control

Pain signals are not simply relayed from the periphery to the brain. The spinal cord dorsal horn acts as a filter where incoming sensory input can be amplified or damped before it reaches higher centres. Brainstem circuits sit above this filter and send signals back down. The rostral ventromedial medulla (RVM) is the main output node of the descending pain-modulating system, and its "ON" cells facilitate and its "OFF" cells suppress nociceptive transmission in the dorsal horn. Research in animal models of chronic pain has documented changes in RVM physiology, and a shift toward loss of descending inhibition, increased descending facilitation, or both is considered a contributor to persistent pain in animals and in patients. One proposed explanation for latent sensitization involves constitutive opioid receptor activity in the RVM, which may mask underlying hyperresponsiveness in the ascending circuits. Descending control is not limited to brainstem sources. Anterior cingulate stimulation in rodents has been shown to potentiate excitatory transmission in the spinal cord, and this effect is independent of the RVM. After peripheral nerve injury, spinal synaptic transmission was enhanced, and the cortical facilitation was occluded. A 2026 study in mice identified RVM inhibitory neurons whose activation reduced heat and cold sensitivity across the body, while their silencing produced mechanical allodynia and spontaneous pain-like behaviour. This circuit is thought to underlie the "pain-inhibits-pain" phenomenon, which is reported to be impaired in chronic pain conditions.

Structural and functional changes in the brain and nerves

Neuroimaging studies have described measurable differences in people with chronic pain compared with healthy controls. A 2025 systematic review of brain health found that 17.3% of structural MRI studies reported hippocampal atrophy, and most studies identified lower grey matter volume or cortical thinning in regions also affected in Alzheimer's disease. The same review noted that a minority of studies (about 12%) reported increased grey matter volume, indicating that findings are not uniform. A 2025 individual participant data meta-analysis, which pooled eight datasets across five conditions including knee osteoarthritis, fibromyalgia, chronic low back pain, trigeminal neuralgia and migraine, found small, localized cortical thinning and volume loss in temporo-occipital regions, including the entorhinal cortex, along with widespread increases in intrinsic cortical curvature across 49 of 68 regions. Studies of chronic low back pain have reported reduced grey matter in the dorsolateral prefrontal cortex, altered functional connectivity and lower levels of certain cerebral metabolites. Studies of trigeminal neuropathic pain and temporomandibular disorders point to the thalamocortical pathway as a principal site of plasticity. White matter changes have also been reported, including lower fractional anisotropy in tracts such as the cingulum. Changes in peripheral nerves are described in the neuropathic pain literature, where nerve injury itself alters the sensory pathway. Neuroplasticity, the capacity of neurons and synapses to change with experience, is the proposed link between these findings. Persistent nociceptive input is thought to produce synaptic hyperactivity and remodelling, and brain-derived neurotrophic factor (BDNF) levels are elevated in several pain conditions. The highest levels have been reported in fibromyalgia. Whether these structural changes are causes or consequences of chronic pain remains unresolved.

Altered network connectivity in limbic and affective circuits

Chronic pain is associated with reorganization of large-scale brain networks rather than only with local tissue changes. A meta-analysis of graph-based connectivity metrics found lower local efficiency in resting-state functional networks in chronic pain, which suggests reduced local specialization and a shift toward more global integration. This pattern was present in both chronic primary and chronic secondary pain, while the structural whole-brain topology was not altered. The default mode network has been linked to working memory and cognitive changes in chronic back pain, and it interacts with the medial prefrontal cortex. Studies also highlight the anterior cingulate cortex, insula, amygdala, hippocampus, and the parahippocampal gyrus as regions where pain processing overlaps with emotional regulation. In experimental models of neuropathic pain, dysfunction in the medial prefrontal cortex to periaqueductal grey pathway has been proposed as a cause of diminished descending control. These networks are central to the link between sensory input and negative affect, which is one reason chronic pain is often studied alongside mood disorders.

Molecular overlap with depression

Chronic pain and depression frequently co-occur, and several reviews describe shared molecular pathways that may partly explain this overlap. These include monoamine neurotransmitters such as serotonin, norepinephrine and dopamine; neurotrophic factors such as BDNF; glutamate and its receptor subtypes; and inflammatory mediators. Within the monoamine group, the midbrain dopaminergic system has been proposed to affect neuroplastic changes in both conditions, and persistent pain has been suggested to impair dopamine activity in that region. Glutamate-mediated excitation and reduced GABA-mediated inhibition are thought to contribute both to central sensitization and to the processing of negative emotion. Proinflammatory cytokines, notably interleukin-6 and tumour necrosis factor-alpha, have been linked to microglial activation and central sensitization, and they are proposed to contribute to mood dysregulation as well as to nociplastic pain. Altered BDNF expression is another point of convergence, as it connects neuroplasticity to pain amplification. Neuroimaging studies report overlapping dysfunction in prefrontal, cingulate and limbic networks. Because much of this evidence comes from animal studies or cross-sectional designs, the direction of causation and the specific contribution of each pathway remain under investigation.

Psychological and social factors

The biopsychosocial model treats persistent pain as the product of interacting biological, psychological and social processes rather than a simple readout of tissue damage. In this framework, the nervous system's alarm can keep operating after healing because cognition, mood, sleep and social circumstances shape how strongly input is amplified and how it is interpreted. The model explains why people with similar injuries or similar imaging findings can differ widely in how long their pain lasts and how far it restricts their lives.

Among psychological factors, pain catastrophizing, a pattern of magnifying, ruminating on and feeling helpless about pain, has the most consistent evidence as a predictor. A 2025 systematic review of randomized trials in adults with chronic musculoskeletal pain found that 13 studies reported a significant association between pain catastrophizing and pain-related outcomes, including pain intensity (n = 8), disability (n = 7), and pain interference (n = 3). In a registry study of cancer patients with chronic pain, change in pain catastrophizing emerged as the only significant, independent psychosocial predictor in multivariable models. Catastrophizing also drives avoidance: according to the fear-avoidance account, it leads to an overreaction to pain perception, which intensifies the pain experience and fosters avoidance behaviors. The strength of its effect varies with age. In a developmental comparison, emotional distress was the strongest predictor of pain interference for children, whereas pain intensity was the strongest predictor for both adult groups. Evidence on pain beliefs, coping styles and social support is more heterogeneous, and their contributions are generally smaller and less consistently replicated than those of catastrophizing and distress.

Psychological and physical disturbances tend to feed back on one another. In cancer patients, changes in several psychological factors were significantly associated with worsened pain outcomes over time, including increased pain catastrophizing, depression, anxiety, and sleep disturbance. Depression is among the most frequent companions of chronic pain, and a bidirectional pattern has been described in which a significant bidirectional relationship between pain catastrophizing and depressed mood, decreased quality of life, and higher pain severity and life interference has been reported. Posttraumatic stress disorder shows a similar overlap. A meta-analysis of mediation studies found preliminary evidence that PTSD is indirectly associated with chronic pain via pain catastrophizing and depression, though the authors noted that existing mediation studies are cross-sectional and of generally low quality.

Sleep disturbance is one of the most prevalent links. 24-32% of patients with chronic pain also report experiencing insomnia, as defined by the DSM. This is double the proportion of individuals in the general population. The relationship runs in both directions, although its relative strength is still debated. One narrative review concluded that current evidence suggests that sleep impairment more strongly predicts pain than pain does sleep impairment. Insomnia can also persist after pain and mood improve, which suggests that it needs its own treatment target. Anxiety, depression and sleep problems often coexist, and they can amplify one another's effects on pain.

Socioeconomic position is a consistent factor in both the risk and the course of chronic pain. Individuals of lower SES are more likely to have CP and also to have more severe, disabling pain and more comorbid chronic health conditions. Socioeconomic gradients have also been reported in young adults. A Finnish cohort study of employees aged 18 to 39 found that the strongest associations after adjustments for covariates remained between chronic pain with high disability level and low educational level, with manual occupation and frequent economic difficulties also strongly associated with high-disability pain. The gradient appears to differ by sex in at least some populations, since SES was more strongly associated with CP for men than for women. Lower socioeconomic status is linked to a narrower set of coping options: one review noted that problem-solving was reported less by those of lower SES, and strategies for avoiding or minimising pain, including analgesic use, reported more than in higher SES.

Employment is both a driver and a consequence of chronic pain. Chronic pain has been associated with severe disability, decreased productivity, and exit from the labor market, with a negative impact on financial condition. Workplace conditions also matter. In a review of employment-related factors, lack of modified work and lack of work autonomy predicted chronic pain disability, although this evidence was rated as limited in strength. Financial and occupational flexibility can buffer these effects, as wealthier individuals can afford to work shorter hours, while white collar jobs allow more adjustments for those with disabilities to continue at work. Job loss and early retirement can in turn increase isolation and distress, which spreads into family life. Families of patients have described role reversals, where the patients' responsibilities and duties are shifted to partners, children, or extended family members.

Taken together, these findings suggest that social disadvantage, psychological distress and functional loss form a self-reinforcing cycle. Pain limits work and income, reduced income and reduced social standing increase distress and limit access to care, and distress in turn heightens pain interference. Breaking this cycle requires attention to both psychological processes and the material conditions in which patients live. Research that measures these factors together, preferably over time, remains the main way to clarify their causal roles.

Major clinical syndromes

ICD-11 groups chronic pain into seven main categories: chronic primary pain and six kinds of chronic secondary pain. Chronic pain is classified under "MG30 - Chronic Pain", and subdivided into seven main diagnostic categories. The chronic primary category is a diagnosis in its own right, so its syndromes are defined by the pain itself rather than by a known lesion.

Chronic primary pain conditions

Chronic primary pain is assigned when chronic pain in one or more anatomical regions is associated with significant emotional distress and/or significant functional disability, and the symptoms are not better explained by a secondary diagnosis. Fibromyalgia is the best-known example. ICD-11 places it under chronic widespread pain, and it is regarded as a primary and nociplastic pain condition. Central sensitization is considered the core pathophysiological mechanism in fibromyalgia, but its cause is unclear. The classification is descriptive: classifying Fibromyalgia as a type of chronic primary pain does not imply the empirical judgement that central sensitization or other somatic processes do not play a part.

Nonspecific chronic low back pain is handled similarly. ICD-11 lists chronic primary low back pain within the musculoskeletal subgroup, alongside cervical, thoracic and limb pain. Headache is also included: chronic primary headache or orofacial pain covers chronic migraine and chronic tension-type headache, which are otherwise commonly managed as separate disorders (see migraine and headache).

Neuropathic conditions

ICD-11 defines chronic neuropathic pain as pain due to a lesion or disease of the somatosensory nervous system. Prevalence figures for the best-known forms differ widely, partly because denominators differ. One trial protocol states that painful diabetic neuropathy is the most prevalent type of neuropathic pain, affecting up to 50% of diabetic patients. A systematic review, by contrast, gave the best estimate of overall prevalence of painful DPN in the diabetic population as 15%. Estimates among people with neuropathy alone are lower still, with pain developing in approximately 30–40% of patients with diabetic neuropathy. Risk rises with the duration of diabetes and with age.

Postherpetic neuralgia follows herpes zoster and is defined by pain that lasts for more than 3 months after the onset of a herpes zoster infection. Estimates for its prevalence among patients with zoster range from 7% to 27%, with the figure measured at three months after onset. Its incidence increases in older adults, and the proportion of zoster patients with persistent pain is substantially higher in those over 60.

Pain after stroke is another neuropathic syndrome. The prevalence of CPSP varies, ranging from 1% to 35%, but it is likely underreported, partly because of cognitive or communication impairment. CPSP often remains resistant to standard neuropathic pain treatments, such as anticonvulsants and antidepressants. Pain in multiple sclerosis is also frequently neuropathic in character, arising from demyelinating lesions and central changes, although prevalence estimates are not summarized here.

Chronic postsurgical and post-traumatic pain

ICD-11 describes this group as pain that persists beyond normal healing after surgery or trauma. The median incidence at six to twelve months after surgery is 20–30% with a slight decrease over time, but the range across studies is very wide, largely attributable to methodological differences caused by different methods of data collection and variable definitions. The risk varies by procedure. Although 35–57% of patients with CPSP show signs of neuropathic pain, the incidence for different surgeries varies widely and is highest after thoracotomy, mastectomy and amputation. Persistent pain after amputation can be extreme: a total of 2 years after amputation approximately 60% of amputees report phantom limb pain. Among the mechanisms, peripheral and central sensitization and nerve injury are considered central, and preoperative pain, chemotherapy/radiotherapy, surgical, psychological and genetic factors are recognized risk factors.

After multiple trauma, rates are especially high. In a South Korean cross-sectional study of 100 adults who had undergone thoracotomy for multiple rib fractures, 80% and 65% patients reported any level and above moderate chronic pain, respectively. More than 70% of patients had a current opioid prescription. The same study found 47% and 59% patients were classified as being at risk of above mild-level anxiety and depression. Its authors reported only weak evidence linking severe acute postoperative pain to later chronic pain, so the relationship with trauma severity remains uncertain. Across thoracotomy studies in general, the prevalence of chronic post-thoracotomy pain ranges from 25 to 91%, showing considerable heterogeneity.

Cancer pain and pain in chronic disease

ICD-11 classifies pain caused by cancer or cancer treatment as chronic cancer-related pain (see cancer, chemotherapy and radiation therapy). Persistence after cancer surgery is common: in breast cancer patients, the incidence of any permanent pain 1 and 2 years after surgery decreased from 67% to 45%. Pain in palliative settings is often treated as a separate clinical problem, but many patients with advanced cancer also have chronic pain from earlier treatment.

Pain accompanying heart failure and chronic kidney disease is generally described as multifactorial. It may arise from the underlying disease, from musculoskeletal or ischaemic sources, from treatment-related nerve injury, or from procedures such as dialysis. Because these conditions are classified primarily by their organ-level diagnosis, the pain component is often under-recorded, and it is typically classified as chronic secondary pain when it is coded at all.

Assessment and diagnosis

Assessment of chronic pain aims at more than confirming that pain is present. Clinicians try to establish the mechanism producing the pain and any underlying disease that may be driving it, because treatment choices depend on that knowledge. The goals of diagnosis include estimating prevalence and characterizing patients for clinical and research purposes, but the primary goal is usually to guide treatment, which requires knowing the underlying mechanisms. In practice, the workup usually starts with the patient's account and medical records, then a physical examination, and only afterwards laboratory tests and diagnostic imaging when they are needed to clarify the source of the pain. The history also records timing. Clinicians note the duration and chronicity of pain, and the temporal pattern of the pain (eg, episodic, chronic-recurrent, constant but fluctuating in intensity). For pain that follows a clear trigger, such as trauma or surgery, patients are typically able to report duration accurately.

Mechanistic classification relies heavily on clinical description. The three-category scheme of nociplastic, nociceptive and neuropathic pain was proposed by the International Association for the Study of Pain in 2017. Its application depends mainly on how patients describe spontaneous pain and how they respond to evoked stimuli, and some specialist services have documented diagnoses using a mechanism-based approach in accordance with the ICD-11.

Numerical rating scales are the customary metric for intensity. Patients typically rate pain from 0 to 10, or 0 to 100, with 0 being "no pain" and 10 or 100 "the worst pain imaginable." Verbal descriptors and visual analogue lines are common alternatives. The time frame of the question matters: clinicians may ask about current pain, the best and worst pain over 24 hours, or average pain over the past week, which provides a more stable metric for chronic conditions. The scales have clear limits. Because pain is multidimensional, the scale only measures intensity, and it does not account for the why or how behind a patient's experience. More fundamentally, pain is treated as inherently subjective. Pain is and will remain a subjective experience, and as such is not objectively measurable. A number is therefore a proxy for experience rather than a direct readout of it.

Because persistent pain brings physical, psychological and social impairment, assessment guidance favors multidimensional measures. The Brief Pain Inventory measures pain intensity and the degree of interference with functioning, using a 0-10 numerical rating scale. Broader instruments cover disability and physical functioning, quality of life, emotional functioning, psychosocial aspects, attitudes and beliefs, coping, and other constructs that may have a reciprocal relationship with chronic pain, including fatigue, sleep, addiction, and trauma. Specific tools address particular domains, such as the Pain Catastrophizing Scale, which measures catastrophic thoughts about pain, and the Symptom Checklist-90 Revised, which covers several areas of psychological functioning. The Chronic Pain Grade Scale combines intensity and disability subscores into 5 hierarchical categories: grades 0 (no pain) to IV (high disability-severely limiting). Comprehensive batteries are not always practical; the PROMIS system is psychometrically strong but long and complicated, and not usually feasible in a clinical setting. Where resources are limited, guidance suggests a smaller core set, such as the Pain Interference subscale of the BPI, the Pain Interference scale of the Multidimensional Pain Inventory, and the Pain Disability Index.

There is no accepted objective biomarker for most chronic pain conditions, so self-report and structured screening remain central to diagnosis. For conditions such as chronic low back pain, osteoarthritis, and fibromyalgia, classification depends mostly on self report and less on objective findings like X-ray or magnetic resonance imaging (MRI) changes. Structural findings often correspond poorly with symptoms; for instance, radiographic measures of joint degeneration in osteoarthritis fail to strongly predict the pain experienced by the patient. Neuroimaging has been explored as a candidate marker, but brain imaging is not a surrogate of self-report. Although self-report remains the gold standard for pain assessment, machine learning may aid in the classification of chronic pain disorders. A large machine-learning study using UK Biobank data found that biomarkers derived from blood immunoassays, brain and bone imaging, and genetics were effective in predicting medical conditions associated with chronic pain but not self-reported pain, and that all biomarkers worked in synergy with psychosocial factors, accurately predicting both medical conditions and self-reported pain. Objective markers would be most useful where communication is unreliable, since they may play an important role in pain classification of patients with cognitive/psychological dysfunction and in individuals who are unable to communicate. In settings without self-report, researchers have proposed indirect measures, such as heart rate, galvanic skin response, and pupil dilation, although such signals are indirect and require validation.

Treatment and management

Management of chronic pain generally follows a multimodal principle: several pharmacological and non-pharmacological components are combined, chosen with the dominant mechanism in mind (nociceptive, neuropathic or nociplastic) and adjusted to the individual. The reasoning is largely empirical. Single-drug therapy for continuous chronic pain seldom provides satisfactory relief, and multimodal programmes are typically offered when conventional treatment has produced only a partial response, often in structured rehabilitation settings (Multimodal therapy represents the evolution of care for patients with partial or incomplete responses to conventional treatment). Clinical guidance follows the same logic. The US CDC's 2022 opioid guideline frames chronic pain as a condition best addressed through a multimodal approach.

Analgesics and neuropathic-pain agents

Simple analgesics such as ibuprofen and acetaminophen are commonly used first, while neuropathic pain is more often treated with antidepressants that act on serotonin and noradrenaline pathways, or with anticonvulsant drugs such as gabapentin and pregabalin. Both groups provide a degree of relief in many trials, but the benefit is usually partial and often declines with prolonged use. Finding a balance between effective treatment and acceptable side effects is a key factor in the pharmacological treatment of pain. Common adverse effects include sedation, dizziness, nausea and, for some agents, weight gain or sexual dysfunction. Measured outcomes also tend to be modest. A review of a series of clinical trials on chronic pain sponsored by the pharmaceutical industry considered 30% pain reduction as clinically significant, which indicates how limited a typical response can be. Long-term efficacy data for most of these drugs remain thinner than the short-term trial evidence.

Opioids: benefits, risks and prescribing debate

Opioids such as morphine are used for selected patients, but their role in long-term chronic pain is the most contested part of pharmacological care. The CDC's 2022 guideline, which replaced its 2016 chronic-pain guideline, found insufficient evidence to determine long-term (>1 year) benefits of opioid therapy for chronic pain. It recommends that opioids should be used only when benefits for pain and function are expected to outweigh risks. Nonopioid therapies are preferred for subacute and chronic pain. The guideline applies to outpatients aged 18 and older, and the recommendations do not apply to pain related to sickle cell disease or cancer or to patients receiving palliative or end-of-life care.

Critics of restrictive prescribing argue that some patients with stable function benefit from long-term opioid therapy and may be harmed by abrupt dose reductions, while others emphasise the documented risks. Chronic pain patients are prone to illicit opioid use or medication misuse with doctor-seeking behaviour. Debate therefore centres on how to identify who benefits, how to monitor risk, and how to taper safely, rather than on a single agreed rule.

Psychological, exercise and rehabilitation approaches

Cognitive behavioural therapy (CBT) is among the most studied non-drug options and is included among first-line recommendations for chronic musculoskeletal pain, alongside multicomponent self-management and, for specific conditions, exercise and psychological therapies (First-line recommendations for chronic musculoskeletal pain include cognitive behavioral therapy, multicomponent self-management interventions, and, for specific areas, exercise and psychological therapies.). In a meta-analysis of randomised trials excluding headache, when compared with the waiting list control conditions cognitive-behavioural treatments were associated with significant effect sizes on all domains of measurement, and comparison with alternative active treatments revealed that cognitive-behavioural treatments produced significantly greater changes for the domains of pain experience. Results are less uniform in specific populations. In chronic low back pain, one review found that CBT did not show statistically better results compared to other treatments. Long-term outcomes are also mixed: in one five-year cohort, function continues to improve through 5 years, while pain shows partial recurrence.

Exercise and physical rehabilitation are often delivered together with psychological work. Interdisciplinary programmes may combine physical and psychosocial treatment methods, such as graded activity and pain neuroscience education. Acupuncture is recommended in some guidance with explicit caveats about setting and practitioner training, and its effects are generally modest. Evidence for transcranial direct current stimulation (tDCS) is limited and heterogeneous, with small trials and inconsistent results; it is considered experimental for most pain conditions. By contrast, repetitive transcranial magnetic stimulation has been rated as moderately supported for neuropathic pain in one guideline table, illustrating that neuromodulation evidence varies considerably by technique and condition.

Interventional, surgical and palliative options

When oral treatment and rehabilitation are insufficient, clinicians may consider interventional procedures such as nerve blocks, epidural steroid injections, radiofrequency ablation and spinal cord stimulation. Surgery is generally reserved for specific structural causes, because operative treatment for pain without a clear structural indication has produced inconsistent results. In one study, early multidisciplinary biopsychosocial care was associated with more durable outcomes and lower surgical conversion, though the authors noted that this association was observational. Palliative care has a separate role, focusing on symptom control and quality of life in advanced illness, including cancer, where opioids and other agents are often used under different criteria from those applied to chronic non-cancer pain.

Public health, policy and access

Prevention is largely a question of timing. Pain that has not eased within about three months is usually treated as a reason to reassess the diagnosis and step up care rather than to wait, because the period before pain settles into a persistent pattern is thought to be the window in which intervention matters most. Early multimodal treatment, which combines physical-therapy and graded exercise, cognitive-behavioral-therapy where it is available, and medication chosen according to mechanism, is the usual aim. In practice, routine monitoring in primary-health-care settings is the main way such pain is detected.

Global policy attention has been directed at neuropathic-pain. The International Association for the Study of Pain has made it the theme of its 2026 Global Year, and its planners put the number of people affected at roughly 580 to 830 million people worldwide. The condition arises when disease or injury damages the nervous system, disrupting its normal function and causing ongoing pain. Population surveys place its prevalence among adults at around 7-10%, while data on children remain lacking. The Global Year's agenda centres on producing more rigorous preclinical and clinical evidence and on testing whether precision medicine can work for these patients. The association also engages with policymakers to advocate for evidence-based pain management, equitable access to care, and increased research funding.

The global inequity in pain relief is a central concern of policy work. The Harvard Global Equity Initiative–Lancet Commission of 2017 found that most of the world's population has little or no access to pain control and palliative care, and that most untreated pain and suffering happens in low- and middle-income countries. The inequity is most visible in opioid distribution: the Commission described a "10–90 pain divide", in which the richest 10% of countries possess 90% of distributed morphine-equivalent opioids. The Commission also identified legal restriction as a barrier, noting that many barriers to pain relief are systemic and related to overly restrictive legislation driven by concern about the addictive nature of opioid medicines, known as opiophobia.

Within universal-health-coverage, pain relief is recognised as a core component but is often underfunded in practice. The Commission argued that palliative care and pain relief are essential elements of universal health coverage, and that health entitlements and essential packages typically do not include drugs and other interventions needed for pain control, so financial protection for these services should be an explicit goal of national health-system design.

Barriers to delivering care operate at several levels. In a national qualitative study of the US health-system for veterans, primary care teams face competing pressures from expert guidelines, facility leadership, and patients. Clinicians also reported inadequate support and resources to provide multimodal chronic pain management. Training gaps are part of the problem: a review of barriers to multimodal care cites inadequate reimbursement for behavioral therapy and other non-procedural treatments, lack of trained providers, and opioid-related stigma. Patients are also often sceptical of non-drug options, and a survey of 1,581 people with pain identified cost, insurance coverage and limits, concerns about side effects, a lack of information about options, geographic location, and mobility issues as obstacles to individualised, multidisciplinary care. Under-management is therefore not only a clinical failure but also a product of how care is organised and paid for.

Financing is among the most consistently reported obstacles. In an audit of specialty pain clinics in nine US states, 48.1% did not accept patients with Medicaid, and 54.9% required a referral before accepting patients, and the median wait time for a new appointment was 9 days. Coverage gaps are central: a major barrier is the limited insurance coverage for many non-pharmacological therapies such as cognitive behavioral therapy for pain, acupuncture, and physical therapy, especially under programs like Medicaid. Universal coverage does not guarantee access either. In Australia, which has a universal scheme, past 12-month specialised pain program attendance was reported by less than 10% of a cohort of long-term opioid users, and most people with chronic non-cancer pain do not receive evidence-based multimodal management. Closing this gap requires that benefit packages, referral pathways and workforce training support the full range of rehabilitation and palliative-care options, not only pharmacological treatment.

Research history and conceptual change

For much of the modern era, pain was treated as a direct readout of tissue damage: the more severe the injury, the stronger the sensation, and the pain was expected to fade as the tissue healed. René Descartes helped establish this mechanical picture in the seventeenth century. His Treatise of Man, published posthumously in 1664, described pain as a disturbance that travelled along nerve fibres until it reached the brain. Descartes also studied phantom limb pain and proposed that the experience of pain originated in the brain rather than in the missing limb. In the nineteenth century this view hardened into the specificity theory. Charles Bell's version of it, dating from 1811, held that pain is a distinct sensation with its own sensory pathway. Scientists and philosophers then spent the next century and a half refining it.

The specificity model had clear limits. Its central assumption, that a dedicated line runs from receptor to brain for each kind of pain, could not easily account for the fact that intensity and damage often diverged. Melzack and Wall noticed that some people felt immense pain when damage to the body was minimal, while others with serious traumatic injuries felt little or no pain until later. Clinical observation pointed the same way. Henry Beecher began investigating how subjective psychological states related to objective drug responses, while working with severely wounded soldiers during the Second World War. Phantom limb pain in amputees was likewise difficult to reconcile with a purely peripheral account.

The gate control theory changed this framework. Ronald Melzack and Patrick Wall introduced the "gate control" theory in their 1965 article "Pain Mechanisms: A New Theory" in Science. It was the first theory to propose that the pain experience is not simply a linear process running from peripheral stimulation to central experience. Instead, incoming impulses are modulated in the spinal cord by a gate-like mechanism in the dorsal horn before pain is transmitted onward. Input carried by large, non-painful fibres could close the gate, which offered an explanation for why rubbing an injured area often eases it. The theory also brought psychology into the mechanism itself. Melzack later described it as the first theory of pain to treat the psychological functions of the brain as an active component of pain, with memories, meaning, attention and anxiety recognised as integral parts of the experience.

The theory met considerable skepticism when first proposed in 1965, but despite several modifications its basic conception remained unchanged. Its practical influence was also substantial. The gate-control theory stimulated research that led to new medical devices, such as transcutaneous electrical nerve stimulators. Melzack's later work developed the idea further into a neuromatrix model, which described pain as a distributed brain network output.

A parallel change concerned the status of chronic pain itself. Katz and Rosenbloom, reviewing the fiftieth anniversary of the gate theory, noted that the shift it helped drive changed how the scientific and clinical communities conceptualized pain, moving it from a symptom of a disease to a major health problem in need of attention. This recognition became formal in classification. The ICD-11 took effect on January 1, 2022. Its chronic pain category is divided so that chronic primary pain, which is characterized by emotional distress or functional disability and not better accounted for by another chronic condition, is treated as a health condition in its own right. The classification was developed by an international expert task force of the IASP. By contrast, pain can also be secondary to other underlying health issues.

The move toward mechanism-based and phenotype-driven research is closely tied to this reclassification. Grouping conditions by shared features rather than by organ system is intended to unite conditions that had previously been scattered throughout the ICD and help focus attention on their commonalities and differences. Research into phenotypes is still developing. Neuroimaging studies of chronic pain, for example, have shown inconsistent results, which underscores the need to synthesise evidence on neural mechanisms. The conceptual history thus runs from a single tissue-based explanation, through a gated, centrally modulated model, to a classification that sorts chronic pain by its underlying mechanisms and clinical profile.

Open questions and debates

Whether the three-month cutoff is clinically meaningful

The three-month threshold separates acute from chronic pain largely by convention, and critics argue that the line is arbitrary enough to cause practical problems. Acute pain can be complicated for healthcare professionals to assess and manage when there are concurrent symptoms or conditions, and a fixed duration does not resolve these cases. Life stage is a clear example. A newborn who receives repeated needle sticks may experience each one as brief, yet the pain has been present for most of the child's life. For a baby, less than 3 months is not a "short" duration. Partly for this reason, some researchers have proposed organizing definitions around presumed mechanism rather than duration suggesting instead a focus on presumed mechanism. Age raises a related problem in older adults. Chronological age predicts pain duration and diagnostic delay, but it does not adequately capture biological vulnerability or interindividual variability in pain expression. Survivorship also distorts estimates, because chronic pain is associated with higher mortality, so the oldest surviving cohorts may report less pain than their peers thus, surviving older adults may report less pain.

Chronic pain as a disease or a symptom

It remains contested whether chronic pain should be regarded as a disease in its own right or as a sign of another process. Clinical classifications commonly trace persistent pain to several sources. Chronic pain may be related to unresolved injury (e.g., acute to chronic pain transition), a chronic illness (e.g. arthritis), or most frequently the underlying cause is unknown (idiopathic, primary pain). Those who favour a disease model point to cases in which the nervous system keeps signalling after tissue has healed, and to the existence of ICD-11 categories that describe chronic primary pain as a condition. Those who favour a symptom model emphasize that many cases remain anchored to an identifiable disease, such as cancer, arthritis or multiple sclerosis, and that treating pain as a stand-alone entity may obscure the underlying disorder. The two positions are not fully exclusive, and the answer may vary between primary and secondary pain.

Heterogeneous definitions and measurement

Studies also disagree about what counts as chronic pain, which complicates comparison across epidemiological research. Pediatric reviews describe the prevalence of persistent pain in children as uncertain and debated. Basic definitions vary, and some add a frequency requirement, counting pain that occurs on most days, or every day, for three months or more. High-impact definitions go further by combining several dimensions. In one older-adult cohort, pain was classified as bothersome or high-impact as defined by a combination of pain frequency, severity, and interference. Because each study may choose different thresholds and instruments, the same population can yield very different prevalence figures, which limits meta-analysis and international comparison.

Sex-specific research and neuropathic pain recognition

Sex-specific research is incomplete. A microglia-to-neuron pathway that drives neuropathic hypersensitivity was characterized using only male rodents, and later work suggested that in female mice females do not upregulate P2X4Rs and use a microglia-independent pathway to mediate pain hypersensitivity. Instead, adaptive immune cells, possibly T cells, may mediate pain hypersensitivity in female mice. Human studies show a similar gap, since the lack of sex-specific and sex disaggregated analyses in human work leaves the influence of sex and gender on pain poorly understood. Policy has moved unevenly. In 1993, the NIH Revitalization Act implemented mandatory inclusion of women in clinical research funded by the NIH. Equal representation in preclinical work has only recently been developed.

Neuropathic pain, which arises from damage or disease of the somatosensory system, is also under-recognized. It is under-recognized or misclassified, particularly when it coexists with nociceptive pain. Screening questionnaires help, but they fail to discern 10-20% of patients with clinically diagnosed NeP. In spinal disease, a neuropathic component of pain is often present in patients with spinal diseases, with a frequency ranging from 36% to 55% of patients. Long-term drug treatment adds its own difficulties, since it often leads to developing tolerance and resistance to used medications. The evidence base for sustained benefit over years is therefore thinner than the evidence for short-term relief.

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