What Is Chronic Pain? — A Microphone and an Amplifier, a Sound That Rings On Past Three Months

"There Is Nothing Wrong on the Tests"

A forty-five-year-old office worker tweaks their lower back while lifting moving boxes. For the first few weeks, it hurt enough to make moving hard, and since then it has slowly gotten better. Yet even after half a month, the pain does not fully go away. On days with broken sleep it hurts more, and fearing further injury they even quit the exercise they used to do. When they get imaging done again, the response comes back: "There is nothing major wrong on the tests." On the way home, two thoughts alternate in their mind. One is that there is still a breakdown somewhere that hasn't been found, and the other is whether they are just being too sensitive.

Pain that continues like this for months is not rare. Roughly 27% of adults experience long-lasting pain, and it was more common past the age of 45 (an analysis pooling 52 general population surveys and 289,490 people) (PMID 42024903). Another review estimates it at about one in five people (PMID 41614224).

This article starts from where pain is manufactured, looks in turn at why that pain can linger longer than the injured spot, and why treatment tends toward reclaiming daily life rather than getting rid of a single cause.

Where Pain Is Made

When your hand touches a hot pot, the nerves at your fingertip catch the heat and send a signal upward, and as you pull your hand away, an ache that makes you say "ouch" arrives. This short scene contains two things. The nerves catching and transmitting a dangerous stimulus, and receiving that signal to create the experience called pain.

Medicine calls this pain, and the International Association for the Study of Pain (IASP) revised that definition in 2020 after 41 years (PMID 32694387). Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. This definition calls pain an "experience," includes emotion alongside sensation, and embraces even experiences where the injured site is not distinct.

The signal traveling up from the fingertip has a separate name. Nociception is the process by which nerves catch stimuli that could be harmful to the body and transmit them to the spinal cord and brain. The spinal cord is a central nervous system continuing from the brain down along the inside of the backbones, serving as a pathway where commands and sensations travel between the brain and the body while housing nerve cells. Pain usually begins from such a signal, but it can also arise from activity generated within the nervous system even when outside stimuli do not appropriately touch the ends of sensory nerves (PMID 18003941). Nociception is the signal, and pain is the experience created by receiving that signal.

Acute pain is pain that arrives right after an injury or illness and usually stays for a brief time. This pain is part of the defense protecting the body (PMID 39438166) and is useful for survival (PMID 34062143). When a sprained ankle hurts, you use that ankle less, and during that time the injured site heals.

Even when the same signal enters, the experience differs from person to person. Thoughts and emotions influence how pain is felt, and cultural beliefs and the surrounding society also shape a person's pain experience (PMID 41136126). Comparing it to sound, nociception is a microphone catching sound, the spinal cord and brain are an amplifier that receives, magnifies, and refines that signal, and pain is the sound actually coming out of the speaker. Even if the same sound enters the microphone, the volume of the resulting sound varies depending on how the amplifier is set.

Because pain is an experience created by the nervous system receiving incoming signals, and sometimes without such signals, the degree of pain and the degree of injury do not always move together.

When It Passes Three Months

About 72% of people with newly developed back pain recover within a year, while among those whose back pain is already long-standing, 42% recover within a year (PMID 42295944).

Chronic pain is pain that lasts or recurs for more than three months. The classification created by the IASP working group for the World Health Organization's International Classification of Diseases 11th Revision (ICD-11) uses this threshold and divides chronic pain into two groups (PMID 30586067).

Chronic secondary pain is chronic pain that accompanies an underlying condition such as cancer, nerve damage, surgery or trauma, or joint disease, and is considered, at least initially, a symptom of that condition. Chronic primary pain is pain that lasts for more than three months, brings significant emotional distress or functional disability, and is not better explained by another condition. Back pain without a known name is an example, and this classification notes that in this case, chronic pain can be viewed as a disease in its own right (PMID 30586067).

One review suggests that unlike acute pain, which is useful for protecting the body, it is better to view chronic pain as a disease itself (PMID 34062143). This means that, separately from whether the injured site has healed, the long-lasting pain itself becomes the target of treatment.

The label "chronic primary pain" is applied when no other condition better explains the pain (PMID 30586068). Therefore, screening for underlying conditions comes first. About 90% of people who visit the hospital with back pain have non-specific back pain with no specific underlying disease, but the remainder have underlying conditions such as nerve compression leading to the legs, spinal fractures, infections, or cancer (PMID 42295944). High-quality musculoskeletal pain guidelines consistently recommend first screening for signs of serious disease, while also examining psychological and lifestyle factors (PMID 30826805). However, many of the cancer warning signs listed in back pain guidelines lack clarity regarding their source and diagnostic accuracy (PMID 28708761), so individual warning signs do not automatically determine a diagnosis. What specific signs are evaluated in the case of the back is covered in "What Is Low Back Pain? — Wrinkles in the Spine, Pain Without a Name". The presence of an underlying condition is confirmed through physical examination and necessary tests.

Pain that lasts for more than three months can become a condition that must be treated in its own right.

Three Branches of Pain

The throbbing of a sprained ankle, the burning sensation where shingles has passed, and an all-over body ache where no injury can be found arise through different pathways. Depending on these pathways, pain is divided into three branches (PMID 34062143).

Nociceptive pain is pain arising from nociception that occurs at a site of tissue injury or inflammation. A sprained ankle or inflammation in a joint falls under this category.

Neuropathic pain is pain caused by injury or disease affecting the nervous system itself, which handles the body's sensations. This is a definition refined by a gathering of experts in neurology and the pain field (PMID 18003941). Neuralgia after shingles, injured peripheral nerves, and pain following a stroke or spinal cord injury fall under this, and up to 10% of the general population experience this kind of pain, with most failing to improve satisfactorily with current treatments (PMID 30586071).

The third branch is a name adopted by the IASP in 2017 (PMID 39560415). Nociplastic pain is pain that cannot be fully explained by tissue or nerve damage, arising because the way the nervous system processes pain signals has changed. Pain of this kind occurs more broadly, more intensely, or in multiple places compared to any identifiable tissue or nerve damage, and is accompanied by problems with fatigue, sleep, memory, and mood (PMID 34062144), and is often more sensitive than others to light, smells, or sounds (PMID 38755449). Fibromyalgia is a condition in which pain spread widely across multiple parts of the body persists for a long time, commonly accompanied by problems with fatigue, sleep, memory, and mood. Pain in this branch can come on its own, like fibromyalgia, or arrive mixed with other branches, as in long-standing low back pain (PMID 34062144).

The three branches are not divided like watertight compartments. In reality, both within a single person and among different people, the branches overlap considerably, leading many experts to view pain classification as a continuous band (PMID 34062143). Nociplastic pain is not a new name for pain of unknown origin, nor is it the same thing as chronic primary pain (PMID 41294344). Whether the name is appropriate, and whether other branches must be ruled out first before applying this diagnosis, remains under debate (PMID 41294344).

This distinction connects directly to treatment. One review notes that nociplastic pain responds less to treatments such as anti-inflammatory drugs, opioid painkillers, surgery, and injections (PMID 34062144).

Pain can come from injured tissue, injured nerves, and a nervous system whose way of processing pain has changed, and these three frequently overlap within a single person.

A Hyperactive Amplifier

People with nociplastic pain often have tender spots spread all over their body that hurt when pressed. This is a sign that they feel painful stimuli more intensely, or feel stimuli that should not be painful as painful (PMID 38755449). This hypersensitivity is common in nociplastic pain, but it is not a sign exclusive to it (PMID 39560415).

Central sensitization is a state where the pain circuits in the spinal cord and brain become hypersensitive, reacting more strongly to the same signals and making even stimuli that normally do not hurt feel painful. It happens because nerve cells become more easily excited, the connections between nerve cells pass signals more readily, and the power suppressing signals decreases (PMID 19712899). When this happens, unlike acute nociceptive pain, the pain is not tied to whether an external stimulus is present, how strong it is, or how long it lasts (PMID 19712899). Yet, just as nociplastic pain is not the same thing as chronic primary pain, central sensitization is not the same thing either (PMID 41294344).

If you compare it to an amplifier, the amplification level is turned up so that even a quiet sound entering the microphone produces a loud noise from the speaker, and even static that would not normally count as sound becomes noise. This framework explains why pain can continue even after an injured site has healed. One review article summarizes the reason chronic pain persists as the body's protective nociception shifting into a state of maladaptation across the nervous, immune, and mental systems (PMID 41614224). Another narrative review views the transition from acute to chronic not merely as an accumulation of the consequences of long-term pain, but as an active shifting process (PMID 40642387).

In a study that followed people with recent-onset low back pain using brain imaging for one year, those who initially had stronger connections between two brain regions were more likely to have lingering pain (PMID 22751038). This is the result of a single study, and while the authors interpreted this circuit as being involved as a cause, this remains the interpretation of one study.

There is counter-evidence as well. A critical review where four researchers split into two teams to examine the evidence found no studies meeting their causal criteria showing that central sensitization causes chronic pain in humans, found no evidence reporting that central sensitization occurs in humans, and pointed out that studies often confuse pain measurement results with central sensitization measurement results (PMID 39278607). There is also still no diagnostic test to directly confirm altered pain processing within a single person (PMID 39560415).

Still, the road is not closed. One review suggests that quality of life indicators and these nervous system changes can also be reversed with appropriate pain management (PMID 34062143).

The analogy holds true only up to this point. An amplifier merely magnifies sound, but the nervous system assigns a meaning of danger to incoming signals, and sleep, mood, and memory interfere with that intensity. An amplifier has an off switch, but the nervous system does not have a single off switch.

<!-- FIG: Microphone, Amplifier, and Speaker — The top box shows acute pain (speaker volume matches the sound level entering the microphone), and the bottom box shows a state with increased amplification (quiet sounds and static become loud noises). Small tags reading "Spinal Cord and Brain" and "An Explanatory Framework Not Proven as a Cause" are placed by the amplifier. -->

Central sensitization is a leading framework explaining why an injury and pain move independently, but it has not been proven as the cause of human chronic pain.

A Condition Where the Whole Body Hurts, Fibromyalgia

People with symptoms of fibromyalgia make up 2% to 4% of the general population, and far fewer actually receive this diagnosis (PMID 27189527). It is an illness where widespread body pain overlaps with unrefreshing sleep, physical exhaustion, and the difficulty of cloudy thinking (PMID 27189527).

This disease is embroiled in debate. Its definition, how it arises, and its treatment are all under debate, and some people even question whether the illness exists at all (PMID 27189527). A 2009 review saw it, at least in part, as a condition where pain processing in the central nervous system has changed (PMID 19962494), and a recent review views the central nervous system as reacting excessively to sensory stimuli across the board (PMID 42456138). However, fibromyalgia is not always a textbook example of nociplastic pain (PMID 41294344).

A diagnosis is made by listening to a typical cluster of symptoms and checking through physical examination that no other bodily illness sufficiently explains those symptoms (PMID 27189527). Complete recovery from fibromyalgia is rare, but most cases can be well managed within primary care (PMID 42456138). Guidelines emphasize using medications and non-drug treatments together, tailored to the symptoms (PMID 27189527).

The Interlocking Ring With Sleep, Mood, and Fear

About 39% of people with chronic pain had clinically meaningful depressive symptoms, and about 40% had anxiety symptoms (an analysis pooling 347,468 people across 50 countries) (PMID 40053352). It was highest in fibromyalgia samples, where depressive symptoms were 54%, and lowest in arthritis samples such as osteoarthritis, where osteoarthritis was 29% (PMID 40053352).

While it is widely known that pain brings distress and sleep problems, a review notes that many doctors are unaware that the relationship runs both ways (PMID 34062143). Sleep is an example. In an analysis pooling 16 studies that followed people recruited in advance, people who had sleep problems at the start showed a higher likelihood of developing chronic musculoskeletal pain later (PMID 38809241). Conversely, the side where pain brings later sleep problems appeared over short periods, and over long periods appeared only in widespread pain while the rest of the evidence was very uncertain, leading the authors to conclude that the claim of bidirectional influence needs further confirmation (PMID 38809241). People who have both pain and sleep problems experience stronger and longer-lasting pain, greater disruption to daily life, and move less (PMID 31909797).

Fear also forms a loop. Fear-avoidance is a reaction of avoiding movement and activity out of fear that it will hurt or cause further injury. Fear of pain and avoidance behaviors contribute to lowering physical strength and increasing everyday disability (PMID 41136126). One review notes that in long-lasting musculoskeletal pain, it is widely accepted that fear of movement, catastrophizing, anxiety, and nervous system sensitization following long-standing pain account for a major share of pain and disability (PMID 28371175).

There is a framework that views this interlocking picture of body, mind, and daily life as a single whole. The biopsychosocial model is a perspective that views problems in health and function as being shaped together by the body, mind, and social environment. In this framework, pain and disability are the ever-changing result of physical, psychological, and social factors continuously influencing one another (PMID 29408484).

Chronic pain interlocks with sleep, mood, and fear, and the strength of the evidence varies for each direction of that loop.

The Phrase "It's All in Your Mind"

We return to the place where that person first asked, "Am I being too sensitive?" When a doctor recommends psychological therapy or pain education, it is easy for this advice to sound like "the pain comes from your mind."

The diagnostic classification for chronic primary pain views all pain as involving a combination of physical, psychological, and social factors, and allows this diagnosis to be applied regardless of whether a physical or psychological cause has been found (PMID 30586068). This means the diagnosis does not depend on finding a psychological cause. What is pointed to as the basis for nociplastic pain is also a change in how the central nervous system processes pain and sensation more loudly and how it modulates pain (PMID 34062144). Seen through the amplifier metaphor, the place that magnifies the pain is also inside the body, within the nervous system. However, as we saw earlier, this mechanism has not yet been proven as a cause.

Education looks in the same direction. Pain neuroscience education teaches patients how pain is generated in the nervous system, helping them reunderstand their pain as something less threatening. This education helps reframe pain not as a sign that tissue is damaged, but as a sign that the nervous system has decided the body needs protection; it does not end with advice on behavior or thoughts, nor does it deny the contribution of signals coming up from injured tissue (PMID 26051220). There is also a critique that the biopsychosocial model is often narrowed back down to bodily medicine, fragmented, or reduced to a single factor in practice (PMID 35645164).

Recommending psychological therapy does not mean the pain is your fault (PMID 30586068, PMID 26051220). Thoughts, emotions, and behaviors are ingredients that go into creating the experience of pain, which is why an approach that cares for both the mind and the body together is considered necessary (PMID 41136126). Changing those ingredients becomes one branch of treatment.

There is a misunderstanding in the opposite direction, too. It is the idea that if you find a single cause and eliminate it, you will get better. Nociplastic pain responds less to surgery, injections, and certain medications (PMID 34062144), and patients who misunderstand the cause of their symptoms are prone to chasing unnecessary tests and treatments (PMID 37011956). That does not mean finding causes is useless. The underlying disease we saw earlier is a cause that must be found (PMID 42295944).

Treatment Aims to Restore Function

Clinical trials and guidelines for chronic pain generally recommend a multidisciplinary approach where various treatments tailored to an individual (such as medication, psychotherapy, and procedures) are used together by multiple professions, and their goals include functioning despite pain and accepting pain (PMID 34062143).

Exercise is the first piece. Physical activity, when used at the right frequency, duration, and intensity, improves pain and its associated symptoms, and while there are no strict guidelines, moving frequently is better than sitting for long periods (PMID 26267006). This review summarizes that it works best when tailored to the individual and increased gradually (PMID 26267006). For long-standing musculoskeletal pain, there is agreement on exercise that is personalized, safe, and perceived as non-threatening, but there are many uncertainties regarding how to design an exercise prescription (PMID 28371175). In chronic low back pain, most exercises were better than minimal treatment, and the authors of that analysis recommended doing an exercise one enjoys so that it can be sustained consistently (PMID 34538747).

Cognitive behavioral therapy is a drug-free treatment designed to change thoughts about pain and the resulting behavioral habits. In an analysis by Cochrane, an international organization that synthesizes medical evidence, pooling 75 psychotherapy trials for chronic pain, cognitive behavioral therapy slightly reduced pain, disability, and distress compared to usual care, and the difference was very small when compared to other active treatments (PMID 32794606). The effect compared to usual care generally continued during the follow-up period, but the effect compared to active treatments did not. The authors concluded that the effects of cognitive behavioral therapy were small or very small, and noted that there was insufficient evidence to judge side effects (PMID 32794606).

Acceptance and commitment therapy is a psychotherapy that helps, rather than striving to eliminate pain, make room to pursue activities one values while living with pain. In an analysis pooling 12 randomized trials, acceptance and commitment therapy improved daily functioning immediately after treatment with low to moderate certainty evidence, but whether the effects persisted was mixed (PMID 34536462). The same Cochrane analysis considered the evidence for acceptance and commitment therapy to be very uncertain (PMID 32794606).

The effect of pain neuroscience education is also modest. Compared to control groups, the magnitude by which this education reduced pain and disability was clinically trivial even in the short term, while fear of movement was significantly reduced in the short term (PMID 30831273). In chronic low back pain, this education alone reduced pain in the short term, but long-term effects were mixed, and pain was reduced further when used alongside physical therapy or exercise (PMID 41005108). In chronic low back pain, psychotherapy was most effective when combined with physical therapy, mainly structured exercise, and cognitive behavioral therapy combined with pain education clinically meaningfully improved daily functioning immediately after treatment (PMID 35354560).

Multidisciplinary rehabilitation programs addressing body, mind, and work together also reduced pain and disability more than usual care in chronic low back pain, but the magnitude was about 0.5 points on a 10-point pain scale (PMID 25694111). The authors of the same Cochrane analysis noted that the effect is not large and should be weighed against the time and resources required for the program (PMID 25180773).

Sleep is also a place for treatment. Insomnia cognitive behavioral therapy is a drug-free insomnia treatment designed to change thoughts about sleep and bedtime habits. Even in people with chronic pain, insomnia cognitive behavioral therapy durably improved sleep (PMID 31909797).

Medication is a piece placed on top of that. Opioids are a group of potent painkillers that suppress pain signals in the brain and spinal cord. The 2022 guidelines from the Centers for Disease Control and Prevention (CDC) address whether to start these drugs, how much to use, and how to monitor their harms—listing use disorder, overdose, and death as those harms—and recommend weighing the benefits and risks of any treatment against the individual's circumstances, while also noting that this recommendation should not be used as a standard applied identically to every patient (PMID 36327391). In an analysis pooling 19 studies that reported at least one instance of problematic use such as abuse, misuse, addiction, or dependence among adults using these drugs for non-cancer chronic pain, the rate was 36.3% with very high variability between studies, and these figures were mostly measured via questionnaires in U.S. pain specialty clinics (PMID 33528858). A review notes that these drugs should be avoided in nociplastic pain (PMID 39560415). Reducing or changing current medications is determined with the prescribing physician.

Certain classes of antidepressants and anticonvulsants have been used for fibromyalgia, neuropathic pain, and chronic low back pain (PMID 39449766). In an analysis pooling 20 randomized trials, certain drugs showed clear short-term effects in fibromyalgia. In neuropathic pain and chronic low back pain, treatments including tricyclic antidepressants showed no statistically clear benefit, and for some anticonvulsant classes used in neuropathic pain, there was insufficient data to judge their effects. Long-term benefits were inconsistent for any of the drugs (PMID 39449766). The authors noted that variability between studies was very high, requiring cautious interpretation, and that these drugs should not be prematurely dismissed as ineffective (PMID 39449766). Which medication to use or change is decided with the prescribing physician.

The treatment of chronic pain places weight on recovering one's life by altering movement, thoughts, and sleep together, and the effects of each individual component are small to moderate in size.

That Back, Once Again

We hold the facts from before up against that person one by one. The pain has lasted half a year, so it meets the criteria for chronic pain. Most people whose backs begin to ache have no specific disease, but some do have an underlying condition (PMID 42295944), so sorting those out is the task of an examination and necessary tests. If an underlying disease is ruled out and the pain brings along suffering or a disruption in daily life, that pain can be classified under the name chronic primary pain—a pain that must be treated in its own right (PMID 30586067).

How much nervous system sensitization is involved in this person's pain cannot be measured separately with current tests, nor has it been proven to be the cause (PMID 39278607). Hurting more on days of broken sleep and stopping exercise for fear of pain overlap with the loops where sleep and fear lock into pain (PMID 31909797, PMID 41136126).

Treatment moves toward touching several places in this loop together. As the initial treatment for long-standing back pain, exercise of any kind, psychological therapies like cognitive behavioral therapy, and multidisciplinary treatment combining the two are recommended (PMID 42295944). The current evidence is that the effect of each is small or moderate (PMID 32794606, PMID 25180773, PMID 34538747). Even with long-standing back pain, 42% recover within a year (PMID 42295944). How to tailor this sequence for this person is a matter to be decided with a doctor in the clinic.

Where to Look Next

How much central sensitization contributes as a cause in people's chronic pain has not yet been proven (PMID 39278607). The criteria for identifying nociplastic pain need to be tested and refined further in the field, and guidelines for medication and psychological treatments tailored to the three categories are also tasks for the future (PMID 41294344). Whether the effects of psychological treatment and pain education last long-term in long-standing low back pain is still uncertain (PMID 35354560).

The mismatch between imaging and pain is first encountered in "What Is Knee Osteoarthritis? — The Door Frame That Changes With the Hinge" and "What Is Low Back Pain? — Wrinkles in the Spine, Pain Without a Name". The low back pain piece covers fear-avoidance and cognitive behavioral therapy in the context of low back pain.

The loop between sleep and pain continues in "Sleep Loss — A Debt Built Night by Night, Reminders That Lag Behind" and "Insomnia and Sleep Apnea — The Alarm That Won't Switch Off, the Airway That Closes". The story of the nervous system changing according to its use continues in "Neuroplasticity — A Brain That Builds New Roads Beside the Broken Ones", and treatment as the work of recovering function continues in "Rehabilitation — Starting to Plan a Livable Home as the Fire Is Brought Under Control".

Long-lasting shoulder pain and tendon pain are examined in "What Is Shoulder Pain? — A Ball on a Shallow Socket, Hands That Hold and Pockets That Wrap" and "What Is Tendinopathy? — A Rope That Lags Behind, a Load That Arrives Too Soon", and muscle loss in "What Is Sarcopenia? — A Savings Account Filled and Drained Daily, Strength Fading Faster Than the Balance".

Source Papers

• "Prevalence of chronic pain in the general population: A systematic review and meta-analysis." (2026) — PMID 42024903 — Pooled chronic pain prevalence of 26.99% across 52 studies involving 289,490 participants aged 18 to 95 in the general population, 46.7% in those over 45 vs 24.2% in ages 18 to 45, 31.42% in women vs 21.63% in men (P=0.07), with no regional differences.
• "Pathophysiology of Chronic Pain." (2026) — PMID 41614224 — Chronic pain affects 1 in 5 people, persisting as protective nociception shifts into an maladaptive neural, immune, and psychological state, requiring integrated treatment as a systemic disease (narrative review).
• "The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises." (2020) — PMID 32694387 — The 1979 definition was revised in 2020 to "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage," adopted unanimously by the IASP Council.
• "Neuropathic pain: redefinition and a grading system for clinical and research purposes." (2008) — PMID 18003941 — Pain typically stems from nociceptive afferent nerve activity driven by tissue-damaging stimuli, but can also arise from activity within the nervous system without appropriate stimulation of peripheral sensory endings, redefining neuropathic pain as "pain caused by a lesion or disease of the somatosensory nervous system."
• "Neuroplasticity in the transition from acute to chronic pain." (2024) — PMID 39438166 — Acute pain is typically a temporary sensation that serves as part of the body's defense mechanism, progressing to chronic pain in some individuals.
• "Chronic pain: an update on burden, best practices, and new advances." (2021) — PMID 34062143 — Exceeding 30% in some studies, unlike acute pain which has survival value, chronic pain is better viewed as a disease, showing substantial overlap with nociceptive, neuropathic, and nociplastic classifications (a continuum), bidirectional links between pain-distress and sleep, reversible potential of neuroplastic changes, and recommendations for personalized, multimodal, multidisciplinary care.
• "Pain Psychology." (2025) — PMID 41136126 — Cognitive and emotional factors influence pain perception, cognitive behavioral therapy reconstructs the pain experience and improves coping, fear and avoidance of pain contribute to physical deconditioning and disability, and cultural beliefs and social environments shape the pain experience.
• "Low Back Pain: A Review." (2026) — PMID 42295944 — About 90% is non-specific, with specific conditions including radiculopathy, spinal stenosis, fracture, axial spondyloarthritis, infection, and malignancy; roughly 72% of acute non-specific low back pain recovers within 12 months while 42% becomes chronic, and first-line treatment for chronic pain consists of all types of exercise, psychological therapy (such as cognitive behavioral therapy), and multidisciplinary care.
• "Chronic pain as a symptom or a disease: the IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11)." (2019) — PMID 30586067 — An IASP working group in collaboration with the WHO defined chronic pain as lasting or recurring for more than 3 months, designating conditions like fibromyalgia and non-specific low back pain as diseases in their own right termed "chronic primary pain," alongside six categories of "chronic secondary pain" (cancer, neuropathic, visceral, posttraumatic/postsurgical, headache, and musculoskeletal), with the goal of recognizing chronic pain as a health condition in its own right.
• "The IASP classification of chronic pain for ICD-11: chronic primary pain." (2019) — PMID 30586068 — Lasting more than 3 months, associated with significant emotional distress or functional disability, and not better explained by another condition within a biopsychosocial framework, allowing diagnosis regardless of identified biological or psychological contributing factors unlike DSM-5 and ICD-10.
• "The IASP classification of chronic pain for ICD-11: chronic neuropathic pain." (2019) — PMID 30586071 — Encompassing trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and radiculopathy, alongside pain from spinal cord and brain injury, post-stroke, and multiple sclerosis, affecting up to 10% of the general population, the majority of whom fail to achieve satisfactory relief from current treatments.
• "The concept of nociplastic pain-where to from here?" (2024) — PMID 39560415 — Adopted by the IASP in 2017 as "pain that arises from altered nociception," with 4 musculoskeletal criteria (such as lasting over 3 months), pharmacotherapy similar to neuropathic pain but avoiding opioids, and understanding mechanisms as a prerequisite for developing diagnostic tests.
• "Nociplastic pain: towards an understanding of prevalent pain conditions." (2021) — PMID 34062144 — A third category distinct from nociceptive (tissue inflammation and damage) and neuropathic (nerve injury) pain, involving central nervous system pain and sensory processing amplification coupled with altered pain modulation, presenting with widespread or intense multifocal pain, fatigue, sleep disturbances, memory issues, and mood problems disproportionate to identifiable injury, appearing standalone like fibromyalgia or mixed like chronic low back pain, and showing reduced response to peripherally directed treatments such as anti-inflammatory drugs, opioids, surgery, or injections.
• "Deciphering nociplastic pain: clinical features, risk factors and potential mechanisms." (2024) — PMID 38755449 — Arising or maintained by altered nociception without tissue damage, accompanied by multifocal pain, fatigue, sleep disturbances, cognitive issues, depression, and anxiety, alongside widespread tenderness (hyperalgesia and allodynia) and heightened sensitivity to light, odors, and sound.
• "Nociplastic Pain: Facts, Controversies and Future Tasks." (2026) — PMID 41294344 — Nociplastic pain is distinct from chronic primary pain and central sensitization, and is not simply a new label for pain of unknown origin, with ongoing debates over terminology and exclusion criteria, fibromyalgia not always serving as a pure prototype, and remaining tasks including field testing criteria and developing treatment guidelines for medication and psychotherapy based on the three types.
• "Central sensitization: a generator of pain hypersensitivity by central neural plasticity." (2009) — PMID 19712899 — Enhanced function (amplification) of nociceptive pathway neurons and circuits driven by increased membrane excitability and synaptic efficiency alongside reduced inhibition, which unlike acute nociceptive pain becomes dissociated from the presence, intensity, or duration of peripheral noxious input, reacting with hypersensitivity even to normal inputs.
• "Decoding pain chronification: mechanisms of the acute-to-chronic transition." (2025) — PMID 40642387 — Chronification is a multidimensional and active pathophysiological process rather than merely the consequence of prolonged nociception (narrative review).
• "Corticostriatal functional connectivity predicts transition to chronic back pain." (2012) — PMID 22751038 — A 1-year longitudinal brain imaging study of subacute low back pain patients showed that nucleus accumbens-prefrontal cortex functional connectivity predicts pain persistence, with the authors suggesting a causal involvement (single study).
• "Is chronic pain caused by central sensitization? A review and critical point of view." (2024) — PMID 39278607 — A review by 4 authors across two teams found no studies fulfilling three criteria for causality and located no evidence reporting the occurrence of central sensitization in humans, noting that pain assessments are often confused with measures of central sensitization.
• "Fibromyalgia." (2015) — PMID 27189527 — Characterized by chronic widespread pain, sleep problems, fatigue, and cognitive difficulties, with ongoing debates over definition, etiology, and treatment, and some even disputing its existence, showing a symptom prevalence of 2 to 4% and a much lower diagnosed prevalence, diagnosed via typical symptom clusters combined with the exclusion of other bodily illnesses, and guidelines emphasizing multi-modal non-pharmacological and pharmacological treatment.
• "Fibromyalgia: an overview." (2009) — PMID 19962494 — Chronic widespread musculoskeletal pain lacking other causes such as tissue inflammation or damage, featuring hyperalgesia and allodynia driven at least in part by central pain processing disorders.
• "Fibromyalgia." (2026) — PMID 42456138 — The central nervous system becomes hypersensitive to sensory stimuli overall, and while a complete cure is rare, most cases can be well managed in primary care.
• "Prevalence of Depression and Anxiety Among Adults With Chronic Pain: A Systematic Review and Meta-Analysis." (2025) — PMID 40053352 — Across 376 studies in 50 countries involving 347,468 participants, depression symptoms stood at 39.3% and anxiety symptoms at 40.2%, peaking in fibromyalgia samples (54.0% for depression) and lowest in osteoarthritis samples (29.1% for depression), with higher rates in women, younger populations, and nociplastic pain.
• "The bidirectional relationship between sleep problems and chronic musculoskeletal pain: a systematic review with meta-analysis." (2024) — PMID 38809241 — In 16 prospective cohorts involving 116,746 participants, baseline sleep problems increased the risk of chronic musculoskeletal pain (short-term OR 1.64, long-term 1.39), whereas the reverse direction showed a short-term OR of 1.56 and a long-term OR of 2.0 only for widespread pain while remaining highly uncertain elsewhere, indicating that bidirectional links require further verification.
• "Chronic Pain and Sleep Disturbances: A Pragmatic Review of Their Relationships, Comorbidities, and Treatments." (2020) — PMID 31909797 — Co-occurrence of both conditions is linked to greater pain intensity, longer duration, higher disability, and lower physical activity, while cognitive behavioral therapy for insomnia long-term improves sleep in chronic pain patients.
• "Exercise for chronic musculoskeletal pain: A biopsychosocial approach." (2017) — PMID 28371175 — It is widely accepted that secondary pathologies resulting from persistent pain—such as fear of movement, catastrophizing, anxiety, and nervous system sensitization—serve as primary contributing factors to pain and disability, with consensus supporting personalized, supervised, safe, and non-threatening exercise, though considerable uncertainty remains regarding prescription implementation.
• "Evaluating psychosocial contributions to chronic pain outcomes." (2018) — PMID 29408484 — The biopsychosocial approach explains pain and disability through a multidimensional and dynamic integration where physiological, psychological, and social factors mutually influence one another.
• "Fifteen Years of Explaining Pain: The Past, Present, and Future." (2015) — PMID 26051220 — Reconceptualizing pain from a marker of tissue damage into a marker of the need to protect the body, this approach does not consist of behavioral or cognitive advice nor deny the contribution of peripheral nociceptive signals, and yields reductions in catastrophizing alongside short-term decreases in pain and disability.
• "The biopsychosocial model is lost in translation: from misrepresentation to an enactive modernization." (2023) — PMID 35645164 — The biopsychosocial model is applied in a biomedicalized, fragmented, and reductionist manner and implemented only partially in clinical practice (critical narrative review).
• "Central sensitization, chronic pain, and other symptoms: Better understanding, better management." (2023) — PMID 37011956 — Patients misunderstand the causes of their symptoms and pursue unnecessary tests and treatments, making clinician patient education influential for perception, management, function, and quality of life.
• "Physical exercise as non-pharmacological treatment of chronic pain: Why and when." (2015) — PMID 26267006 — Physical activity of appropriate frequency, duration, and intensity significantly improves pain and related symptoms; while rigid guidelines are absent, frequent movement outperforms a sedentary lifestyle, with personalized and progressive progression proving most successful.
• "Some types of exercise are more effective than others in people with chronic low back pain: a network meta-analysis." (2021) — PMID 34538747 — Across 217 trials involving 20,969 participants, most exercises outperformed minimal treatment, and while certain types yielded superior efficacy, enjoyable exercises are recommended to foster adherence.
• "Psychological therapies for the management of chronic pain (excluding headache) in adults." (2020) — PMID 32794606 — In a Cochrane review of 75 trials, cognitive behavioral therapy yielded small benefits over usual care and very small benefits over active controls regarding pain, disability, and distress, with effects compared to usual care largely sustained at follow-up unlike those compared to active controls, while evidence for adverse events remained scarce and evidence for behavioral therapy and acceptance and commitment therapy stayed highly uncertain.
• "Acceptance and Commitment Therapy for chronic pain on functioning: A systematic review of randomized controlled trials." (2021) — PMID 34536462 — Across 12 randomized trials, low- to moderate-quality evidence indicated improvements in functioning immediately following treatment, though maintenance over time remained mixed.
• "Pain Neuroscience Education for Adults With Chronic Musculoskeletal Pain: A Mixed-Methods Systematic Review and Meta-Analysis." (2019) — PMID 30831273 — In 12 randomized trials involving 755 participants, effects on pain and disability showed low clinical relevance both short- and medium-term, whereas fear of movement decreased by clinically meaningful margins in the short term.
• "The effectiveness of pain neuroscience education in people with chronic non-specific low back pain: An umbrella review with meta-analysis." (2025) — PMID 41005108 — Across 19 systematic reviews involving 5,200 participants, pain education alone reduced short-term pain with inconsistent long-term effects, while pairing it with physical therapy and exercise amplified pain reduction.
• "Multidisciplinary biopsychosocial rehabilitation for chronic low back pain: Cochrane systematic review and meta-analysis." (2015) — PMID 25694111 — Across 41 trials involving 6,858 participants compared to usual care, multidisciplinary rehabilitation yielded a standardized mean difference (SMD) in pain of 0.21 (roughly 0.5 points on a 10-point scale) and a disability reduction of about 1.5 points on a 24-point scale, supported by moderate-quality evidence.
• "Multidisciplinary biopsychosocial rehabilitation for chronic low back pain." (2014) — PMID 25180773 — Effects were modest and must be weighed against the time and resources required, making referrals appropriate primarily for individuals showing indicators of significant psychosocial impact.
• "CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022." (2022) — PMID 36327391 — Encompassing four domains covering initiation, selection and dosage, duration and follow-up, and risk assessment—where harms involve use disorders, overdose, and death—clinicians should carefully weigh the benefits and risks of all treatments against individual patient circumstances without applying rigid standards.
• "Prevalence of Problematic Use of Opioids in Patients with Chronic Noncancer Pain: A Systematic Review with Meta-analysis." (2021) — PMID 33528858 — Across 19 studies (largely from the US, pain specialty clinics, and mainly using questionnaires), problematic use—defined as reporting any single instance of abuse, misuse, addiction, dependence, or aberrant behavior—stood at 36.3% (I²=99.64%).
• "Non-opioid psychiatric medications for chronic pain: systematic review and meta-analysis." (2024) — PMID 39449766 — Out of 29 trials evaluated via meta-analysis of 20, certain drugs showed short-term efficacy in fibromyalgia, whereas treatments including amitriptyline and desipramine failed to reach significance for neuropathic pain and chronic low back pain, data remained insufficient to judge medications like gabapentin and pregabalin for neuropathic pain, long-term benefits proved inconsistent, heterogeneity ran very high, and clinicians should avoid jumping to the premature conclusion that treatments are ineffective.
• "What does best practice care for musculoskeletal pain look like? Eleven consistent recommendations from high-quality clinical practice guidelines: systematic review." (2020) — PMID 30826805 — Eleven common recommendations drawn from 11 high-quality clinical practice guidelines on musculoskeletal pain (covering back, osteoarthritis, neck, and shoulder) included patient-centered care, screening for red flag conditions, assessing psychosocial factors, selective imaging use, physical examination, education, and exercise.
• "Most red flags for malignancy in low back pain guidelines lack empirical support: a systematic review." (2017) — PMID 28708761 — Out of 13 malignancy red flags across 16 guidelines, sources and diagnostic accuracy remained unclear for many, leaving only a "history of cancer" and "strong clinical suspicion" supported by evidence of accuracy.
• "Psychological interventions for chronic, non-specific low back pain: systematic review with network meta-analysis." (2022) — PMID 35354560 — Across 97 trials involving 13,136 participants, psychological therapy paired with physical therapy proved most effective, with cognitive behavioral therapy and pain education yielding clinically important improvements in function immediately post-treatment, while pain education and behavioral therapy showed the most sustained yet still uncertain long-term effects.