Pain science: central sensitization and chronic pelvic pain

Central sensitization is a term for a change in how the spinal cord and brain handle pain signals: the nervous system becomes more responsive, so pain can be stronger, wider or longer lasting than the amount of tissue injury would predict. Nociplastic pain is the label pain researchers now use for pain that arises mainly from this kind of altered processing. Neither term means the pain is imagined, exaggerated or "in the head." The International Association for the Study of Pain states that a person's report of pain should be respected ^[1], and the changes described under these terms have been measured with sensory testing and brain imaging ^[5][28][31]. In chronic pelvic pain, studies have found signs of sensitization in some women with endometriosis and in some women with no endometriosis found at surgery ^[28][29][31]. Most of those studies are small, observational and cross-sectional, so they describe association rather than cause ^[30]. This article explains the terms, what the research found, how researchers try to measure sensitization, where experts disagree, and what the evidence cannot yet say.

What pain is, and why it differs from nociception

Before sensitization makes sense, the word "pain" needs a careful definition. In 2020 the International Association for the Study of Pain (IASP) revised its definition after a task force of 14 people from several countries reviewed comments from members and the public over two years. The revised text describes pain as an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage ^[1]. The accompanying notes state that pain is always a personal experience shaped to varying degrees by biological, psychological and social factors, that pain and nociception are different phenomena, and that pain cannot be inferred solely from activity in sensory neurons ^[1].

Nociception is the nervous system's detection and signaling of potentially harmful stimuli. Pain is what a person feels. Usually the two travel together, which is why a cut finger hurts. The IASP notes make clear that they can separate. The same notes say that a person's report of an experience as pain should be respected ^[1]. That sentence sets the frame for everything below: a report of pain is taken as real, and the open question is which mechanisms produce it.

Three descriptors: nociceptive, neuropathic and nociplastic

Nociceptive pain is caused by ongoing inflammation and damage of tissues, and neuropathic pain is caused by nerve damage. Nociplastic pain is the term suggested for a third category that is mechanistically distinct from both, arising from altered nociception despite no clear evidence of tissue damage activating nociceptors or of a lesion of the somatosensory system ^[8]. A review of nociplastic pain adds that it can occur alone or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain ^[8].

A Lancet review of nociplastic pain describes it as a third category, mechanistically distinct from nociceptive pain (caused by ongoing inflammation and tissue damage) and neuropathic pain (caused by nerve damage). The authors write that the mechanisms are not entirely understood, and that augmented central nervous system pain and sensory processing and altered pain modulation are thought to play prominent roles. They describe typical features as multifocal pain that is more widespread or intense than the identifiable tissue or nerve damage would predict, together with fatigue, sleep, memory and mood problems. They also state that nociplastic pain can occur alone, as in fibromyalgia, or as part of a mixed-pain state alongside nociceptive or neuropathic pain ^[8].

Fibromyalgia is often used as the reference example of a "centralized" pain condition. A JAMA clinical review reports that fibromyalgia is present in 2% to 8% of the population and is characterized by widespread pain, often with fatigue, memory problems and sleep and mood disturbances, a pattern the author describes as central nervous system pain amplification ^[37].

Chronic pain as a diagnosis in its own right

An IASP working group developed a systematic chronic pain classification for the eleventh edition of the International Classification of Diseases (ICD-11), in cooperation with the World Health Organization. Chronic pain is defined there as pain that persists or recurs for more than three months ^[2]. The classification separates chronic primary pain, in which pain may be conceived as a condition in its own right, from chronic secondary pain, where pain is at least initially a symptom of an underlying disease ^[2].

The chronic primary pain article describes the diagnosis as appropriate when pain has lasted more than three months, is associated with significant emotional distress or functional disability, and is not better accounted for by another condition. It adopts a biopsychosocial framework in which biological, psychological and social factors contribute to each case, and it says the diagnosis is appropriate independently of identified biological or psychological contributors unless another diagnosis better explains the symptoms ^[3].

A companion article covers chronic secondary visceral pain, meaning pain from internal organs of the head, neck, chest, abdomen or pelvis. It states that the intensity of this pain is not necessarily fully correlated with the disease process and that the pain may persist beyond successful treatment of the underlying cause ^[4].

What central sensitization is, at the level of nerves

Central sensitization has been studied in laboratories for decades. A review in Pain by Woolf defines it as a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, triggered by inputs from nociceptors. The review lists how it shows up in people: pain from light touch (dynamic tactile allodynia), spread of tenderness beyond an injured area (secondary hyperalgesia), pain that lingers after a stimulus ends, and enhanced temporal summation, meaning that repeated identical stimuli feel progressively worse. These effects can be elicited quickly in healthy volunteers by experimental noxious stimulation of skin, muscle or viscera, and they come with secondary changes in brain activity that can be detected by electrophysiology or imaging ^[5].

A 2009 review in The Journal of Pain describes the mechanism as an enhancement of the function of neurons and circuits in nociceptive pathways, from increased membrane excitability, stronger synaptic efficacy and reduced inhibition. Because the change sits in the central nervous system, the authors write, the pain is no longer coupled to the presence, intensity or duration of noxious stimuli from the body in the way acute nociceptive pain is. Normal inputs, including touch that usually feels innocuous, can then evoke pain ^[6].

An overview of central sensitization across chronic pain conditions adds that different neuroplastic processes can produce gain or loss of function in the nociceptive system, and that the clinical signs differ by condition. It names local and widespread sensitization, central summation and descending pain modulation as translational mechanisms, and it notes that they can be assessed with quantitative pain testing ^[7].

Woolf also lists open questions. It is not known whether some people have a higher inherited tendency to develop central sensitization, and the review calls for objective biomarkers and agreed diagnostic criteria ^[5]. A rheumatology review notes that, within each pain condition, the presence and magnitude of central sensitization varies widely from patient to patient, and that it has been documented in fibromyalgia, osteoarthritis, rheumatoid arthritis, headache and spinal pain, among others ^[10]. The same review reports that central sensitization predicts poor treatment outcomes in multiple patient populations ^[10].

Why this is not the same as imagined pain

The idea that sensitized pain is "all in your head" survives because of a logical slip. If a scan or surgery shows little or no tissue damage, the reasoning goes, there is nothing to hurt, so the pain must be invented. The research above does not support that reasoning, for four reasons that can be stated from the sources.

First, the IASP definition separates pain from nociception and says pain cannot be inferred solely from sensory neuron activity. A mismatch between visible damage and pain is therefore expected to occur sometimes, and the definition itself says the person's report should be respected ^[1].

Second, central sensitization is a physiological process with measurable consequences. It can be induced experimentally in healthy volunteers, and it changes how neurons respond to the same input ^[5][6]. The mechanism is described in terms of neurons, synapses and reduced inhibition, not in terms of belief or intent.

Third, the changes appear in the data. In pelvic pain studies, researchers have reported lower pain thresholds at body sites far from the pelvis, differences in brain gray matter volume, and differences in brain chemistry and connectivity (described in later sections) ^{[27][29][31][32]}. These are measured differences between groups, reported by independent research teams.

Fourth, the chronic primary pain classification explicitly treats persistent pain without a sufficient explanatory condition as a real diagnosis, appropriate regardless of identified contributors ^[3]. The classification group treats chronic pain as a health condition in its own right ^[2].

Pain is described as influenced by biological, psychological and social factors ^[1][3]. In a study of women with pain suggestive of endometriosis, those with higher anxiety and depression scores were more likely to show sensitization, but the study was cross-sectional and could not tell which came first ^[28]. That finding, like the others in this article, is an association.

How researchers try to detect sensitization

No single accepted test identifies central sensitization in an individual patient. Researchers use several approaches.

Questionnaires. The Central Sensitization Inventory (CSI) is a 25-item self-report form scored from 0 to 100. In its development study, it had a test-retest reliability of 0.817 and an internal consistency (Cronbach's alpha) of 0.879 in a normative group. People with fibromyalgia scored highest and the normative group lowest, and the prevalence of previously diagnosed central sensitivity syndromes followed the same order ^[11]. A follow-up study of 121 patients referred to a multidisciplinary pain center found that 74% met clinical criteria for one or more central sensitivity syndromes. A score of 40 out of 100 best separated that patient group from a comparison group of 129 people who were not patients (area under the curve 0.86, sensitivity 81%, specificity 75%) ^[12].

Sensory testing. Quantitative sensory testing measures thresholds to pressure, heat and cold, and the way pain builds with repeated stimuli. These methods are used in research, and the overview of central sensitization notes that how sensitization appears varies from condition to condition ^[7].

Clinical examination and imaging. Some studies use a clinical exam for allodynia and hyperalgesia, and others use brain imaging. A scoping review of endometriosis research found 30 papers, out of 379 citations retrieved, that mentioned a tool for detecting central sensitization or nociplastic pain. Fourteen studies used only patient-reported questionnaires, six used quantitative sensory testing, two used clinical assessments and eight combined approaches. The authors conclude that there are no standardized methods for detecting central sensitization or nociplastic pain in endometriosis and that the validity of the tools needs further evaluation ^[13].

A registry study looked at a shorter questionnaire, the Pain Sensitivity Questionnaire Minor (PSQ-M), among 983 people with endometriosis. It correlated only weakly with the CSI (r = 0.099), and the authors concluded it may not be the best proxy for central sensitization in endometriosis ^[14].

How common chronic pelvic pain is, and what overlaps with it

Prevalence estimates for chronic pelvic pain depend on the definition and the population. A systematic review of prevalence studies published between 2005 and 2012 found only seven relevant studies and reported prevalence in general ranging from 5.7% to 26.6%. The review points to a lack of consensus on how chronic pelvic pain is defined ^[17]. The GaPP2 trial report states that chronic pelvic pain affects 2% to 24% of women worldwide ^[38]. A UK primary care database analysis covering 284,162 women aged 12 to 70 identified 24,053 chronic pelvic pain cases over five years, with an annual prevalence of 38.3 per 1000 among women who had contacted a general practice. The authors noted that prevalence in the general population is likely to be considerably higher ^[15].

Chronic pelvic pain often occurs with other symptoms. In a postal survey of 2,304 women aged 18 to 49 in Oxfordshire (a 74% response), half of the 483 women with chronic pelvic pain also reported genitourinary symptoms, irritable bowel syndrome or both. Dysmenorrhea (81% versus 58%) and dyspareunia (41% versus 14%) were more frequent in women with chronic pelvic pain than in women without it. Fifty percent of the women with chronic pelvic pain had never received a diagnosis ^[16]. This survey asked about symptoms by questionnaire and did not examine the women.

Among 987 new referrals to a pelvic pain clinic between 1993 and 2000, 35% met Rome I criteria for irritable bowel syndrome. Characteristics associated with irritable bowel syndrome in that group included age 40 or older, depression, six or more pain sites and a history of adult physical abuse. The authors concluded that irritable bowel syndrome and chronic pelvic pain are not simply manifestations of the same disorder ^[19]. That was a cross-sectional study of a specialty clinic population, so it does not show how common these patterns are elsewhere.

A review of chronic overlapping pain conditions describes the high co-occurrence of many common chronic pain conditions and points to shared mechanisms and biopsychosocial influences. The authors argue that trials rarely account for this overlap, so participants may not be representative of many people with chronic pain, and treatment effects may be small when treatments are tested in people with overlapping conditions ^[20].

A genetic study offers one possible clue about shared biology. A meta-analysis of genome-wide association studies that included 60,674 endometriosis cases and 701,926 controls of European and East Asian ancestry found 42 genome-wide significant regions. It found significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back pain and multisite chronic pain, and several implicated genes were linked to pain perception, including NGF ^[21]. A genetic correlation shows that inherited variants are shared in part. It does not show that one condition causes another or that any individual's pain arises from these variants.

The American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin on chronic pelvic pain states that it addresses chronic pelvic pain not completely explained by identifiable pathology of the gynecologic, urologic or gastrointestinal organ systems, and that when the evidence is limited, recommendations are extrapolated from other chronic pain conditions ^[18].

Pelvic sources of pain still matter

Central sensitization does not replace local causes. It sits alongside them, and current reviews of endometriosis pain describe several layers at once.

A review of endometriosis-associated pain states that symptom severity correlates poorly with the extent of macroscopic disease. It discusses pelvic factors, including new nerve fiber growth, peritoneal fluid and inflammation, along with central nervous system and stress system contributions ^[23]. A systematic review of peripheral changes reported that endometriotic lesions and peritoneal fluid had pronounced neuroangiogenic properties: new nerve fibers, a shifted balance of sensory and autonomic fibers in some locations, and raised neurotrophins. Deep infiltrating and bowel lesions had higher nerve fiber densities than peritoneal lesions and endometriomas. The authors state that a clear link between these findings and pain in patients had not been demonstrated ^[24]. An earlier review proposed that new nerve fibers in endometriotic implants may influence dorsal root neurons and increase pain perception, which the authors describe as belief rather than established fact ^[25].

A further review describes endometriosis-associated pain as a product of peripheral sensitization, central sensitization and cross sensitization, and lists comorbid conditions such as bladder pain syndrome, irritable bowel syndrome, abdominopelvic myalgia and vulvodynia. The authors acknowledge limitations in current understanding ^[26].

The practical meaning is that "sensitization" and "disease in the pelvis" are not rival explanations in this literature. Reviews describe nociceptive and nociplastic pain as able to coexist ^[8], and studies in endometriosis are consistent with a mixed picture ^[23][26].

What studies of chronic pelvic pain have reported about sensitization

The following studies are described with their design and size, because both shape what they can show.

A 2003 study compared 10 women with laparoscopically confirmed endometriosis with 10 healthy age-matched women. The researchers injected hypertonic saline into a muscle in the low back, a site where menstrual pain is often felt, and into a hand muscle that served as a distant control site. Pain intensity and pain areas at the hand were greater in women with endometriosis, and pressure hypersensitivity was also reported. At the back site the groups did not differ. The authors interpreted the hand result as central sensitization from persistent nociceptive input ^[27]. The sample was very small.

A cross-sectional prospective study examined 18 women with biopsy-proven endometriosis and pain, 11 women with pain and no endometriosis at surgery, and 20 pain-free volunteers. Participants with pain had laparoscopic excision of suspicious lesions with histologic confirmation. Regional allodynia and hyperalgesia were found in 83% and 82% of the two pain groups and 15% of volunteers. Myofascial trigger points were found in 94% and 91% of the pain groups. Women with any history of endometriosis who had pain had the highest proportion with sensitization (87%, compared with 67% and 15%). Higher anxiety and depression scores, and the presence of myofascial trigger points, were associated with sensitization. The authors suggest that classifying pain by disease, duration and anatomy is inadequate and should be replaced with a mechanism-based evaluation ^[28]. The sample was small.

A study used quantitative sensory testing in 55 healthy women and 37 women with persistent pelvic pain admitted for diagnostic laparoscopy on suspicion of endometriosis. The women with pain had lower thresholds for heat, cold and pressure. Among them, thresholds did not differ between those with biopsy-proven endometriosis (13 women) and those without (24 women). Longer pain duration correlated with lower thresholds. The authors read this as widespread alterations indicative of central sensitization with a time-dependent correlation ^[29]. A cross-sectional design cannot show that longer pain causes lower thresholds, and the group with confirmed endometriosis was small.

A systematic review of central sensitization in urogynecological chronic pelvic pain retained 29 full-text articles, all observational (27 case-control and two cohort studies), of low to good methodological quality. It reported evidence of hyperexcitability of the central nervous system: altered brain morphology and function, generalized hyperalgesia to different stimuli, overactive bottom-up nociceptive mechanisms and autonomic dysregulation. Diffuse noxious inhibitory control appeared normal. The reviewers concluded that the level of evidence was low and that it was unclear whether the central changes are secondary or primary to chronic pelvic pain ^[30].

A narrative review of central changes in chronic pelvic pain and endometriosis reached a similar overall description. It reported changes in behavioral and central responses to noxious stimulation, differences in brain structure (both increases and decreases in volume of specific regions), altered activity of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, and psychological distress. The authors state that the review was not systematic and that pain is often disproportionate to the extent of disease identified ^[22].

Brain imaging studies

A voxel-based morphometry study compared four groups: 17 women with endometriosis and chronic pelvic pain, 15 with endometriosis and no chronic pelvic pain, six with chronic pelvic pain and no endometriosis, and 23 healthy controls, with all patients surgically confirmed. Women with endometriosis-associated chronic pelvic pain had decreased gray matter volume in regions involved in pain perception, including the left thalamus, left cingulate gyrus, right putamen and right insula. Women with chronic pelvic pain without endometriosis had decreased volume in the left thalamus. The endometriosis group without pain did not show these decreases ^[31]. The authors concluded that central pain system changes may play a role regardless of endometriosis. The groups were small, and the design could not show whether the brain differences preceded the pain or followed it.

A later study used proton spectroscopy and resting functional connectivity imaging. Women with endometriosis-associated chronic pelvic pain had higher combined glutamine-glutamate levels in the anterior insula, an area linked to pain processing, and stronger connectivity between that region and the medial prefrontal cortex, compared with pain-free controls. The connectivity was correlated with insula chemistry, anxiety, depression and pain intensity. Women with endometriosis but without pain did not differ from controls ^[32]. As in the first study, these are cross-sectional correlations.

A large network study, the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network, analyzed 1,079 participants with urological chronic pelvic pain syndrome, healthy controls and patients with fibromyalgia. A subset (110 with the syndrome, 23 with fibromyalgia, 49 controls) had brain imaging. People with the syndrome reported pain ranging from localized to widespread. Those with widespread pain had increased gray matter volume and functional connectivity involving sensorimotor and insular cortices, and the same pattern appeared in the fibromyalgia group. Widespread pain was also linked to lower physical and mental function independent of pain severity ^[33]. This was a study of urological pelvic pain, not gynecologic pelvic pain specifically, and imaging was done in a subset of 182 participants.

Reading across these studies, the consistent finding is that group-level differences exist in some brain regions in people with chronic pelvic pain. What remains unresolved is direction and individual meaning. The studies cited here compare groups of people, and none of them presents a brain scan as a test for sensitization in one patient.

Sensitization measures and later pain outcomes

Several observational studies ask whether sensitization measures are associated with how pain looks after endometriosis treatment.

In a prospective cohort at a tertiary center in British Columbia, 239 patients aged 18 to 50 with diagnosed or suspected endometriosis who had surgery and follow-up data more than four months later (a 71.0% follow-up rate, mean follow-up 16.1 months) were analyzed. Higher baseline CSI scores were associated with higher chronic pelvic pain (odds ratio 1.02 per point, 95% confidence interval 1.00 to 1.03), deep dyspareunia, dyschezia and back pain at follow-up, after controlling for baseline pain. The CSI scores themselves barely changed from baseline (43.8) to follow-up (41.7), and people with high baseline scores still had high scores at follow-up ^[35]. A tertiary referral population may differ from other patients, and 29% were lost to follow-up.

A 2026 prospective study of 114 consecutive symptomatic patients at a single tertiary-level referral center looked at hormonal therapy. A CSI of 40 or higher was found in 40.4%. Higher scores, and a CSI of 40 or more, were associated with "hormonal therapy failure" (less than a 30% fall in pain score at six months) for chronic pelvic pain, deep dyspareunia and dyschezia ^[36]. The study is observational, from one center, and covers a short follow-up. It cannot show that sensitization caused the lack of response.

The registry study mentioned above found no change in the PSQ-M and a small change in the CSI after endometriosis surgery, and the authors suggest that surgical treatment of endometriosis does not directly address central sensitization ^[14]. That is the authors' interpretation of two questionnaire results.

A review of endometriosis, sensitization and myofascial pain states that hormonal and surgical therapies target the lesions and do not directly address pain from central sensitization or myofascial dysfunction, which the authors say can continue after traditional treatments are optimized ^[34].

What trials of centrally targeted and multimodal approaches have reported

This section reports study results, not recommendations about what any person should do.

The GaPP2 trial tested gabapentin, a drug that acts on the nervous system, in 306 women aged 18 to 50 at 39 UK hospital centers. Participants had chronic pelvic pain of at least three months and no obvious pelvic pathology at laparoscopy. They were randomized to gabapentin or placebo for 16 weeks. There were no significant differences in worst or average pain scores at weeks 13 to 16 (for worst pain, adjusted mean difference -0.20, 97.5% confidence interval -0.81 to 0.42). More women in the gabapentin group had a serious adverse event (7% versus 2%), and dizziness, drowsiness and visual disturbances were more common ^[38]. Participants had no obvious pelvic pathology at laparoscopy, so the trial population differs from women with identified endometriosis.

A systematic review and meta-analysis of nonpharmacological conservative therapies for chronic pelvic pain included 38 randomized controlled trials with 2,168 women. The authors reported that multimodal physical therapy resulted in lower pain intensity compared with inert or nonconservative treatments in the short and intermediate term, that predominantly psychological approaches showed no difference in pain intensity and a slight difference in sexual function, and that the evidence on acupuncture was too limited to judge ^[39]. A second review of eight studies found that multidisciplinary treatment was associated with lower pain scores (mean difference -2.19) and greater sexual function improvements than single discipline treatment, with no difference in quality of life. The authors rated the certainty of the evidence as moderate to very low and said future research may change the findings ^[40].

The abstracts of these reviews do not report sensitization as an outcome, and the included studies cover different treatments. The Lancet review on nociplastic pain argues that pain of this type responds differently from nociceptive pain, with reduced responsiveness to peripherally directed therapies such as anti-inflammatory drugs, opioids, surgery and injections ^[8]. That is an expert statement from a review. The pelvic pain trials above cannot confirm it.

Where experts disagree

The term nociplastic is not universally accepted. A published reply to the proposal to add a third mechanistic descriptor argued that the new terminology is too vague to help clinical thinking or research, that "altered nociceptive function" was never clearly defined, that central changes such as altered brain networks appear in almost all persistent pain and so do not explain why pain arises, and that claims about better response to centrally acting therapies were unreferenced ^[9]. The author also stresses that pain is a felt experience and that nociceptor activity alone is not pain ^[9]. Those objections concern the label and its explanatory power.

The measurement problem adds to the debate. The CSI was developed to identify central sensitivity syndromes and screens for symptoms across the body, such as those linked to fibromyalgia and irritable bowel syndrome ^[11][12]. Scoring high does not show where the amplification occurs or what is causing it. In endometriosis, reviewers note the absence of standardized detection methods ^[13], and the questionnaires disagree with one another ^[14]. Researchers also state that it is unclear whether central changes are primary or secondary to pelvic pain ^[30].

What this does not tell you

This article describes studies of groups of women. It cannot tell any person whether she has central sensitization, nociplastic pain, endometriosis, adenomyosis or any other condition.

A questionnaire score or a threshold on a sensory test does not identify a cause. The cutoffs discussed here were derived by comparing groups, and the authors of the endometriosis studies report that no standardized method exists ^[12][13].

Evidence of sensitization does not rule out other sources of pain. Peritoneal, bowel, bladder, muscle, nerve and pelvic floor sources can coexist with central changes, and reviews of nociplastic pain describe it as able to occur together with nociceptive or neuropathic pain ^[8]. A normal scan or a surgery without visible lesions is a finding about what was seen, and this article does not treat it as proof that nothing is wrong in the pelvis or as proof of a particular mechanism.

Most pelvic pain studies cited here are cross-sectional, small or from specialty centers. They cannot say whether brain and sensory differences are a cause or a consequence of years of pain, and the 2013 systematic review says so directly ^[30]. Several findings come from different populations (for example urological pelvic pain ^[33]), and results from one condition do not automatically apply to another.

The trial and review results in the treatment section report averages and do not predict how an individual will respond. This article does not recommend, compare or rank treatments. Decisions about evaluation and care belong with a person and her clinician.

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