The Centralized Pain Score: A Method to Identify Nociplastic Pain in Electronic Health Records.

This study was conducted in 3 phases. In Phase 1 we developed the CPS based on ICD diagnostic codes for 8 COPC-related conditions to which empirical central sensitization weights were applied ( Schirle et al., 2023 ). In Phase 2, we performed manual record review of clinical notes to identify patients documented to have clinical “centralized pain” or pain related to “central sensitization”, which became the Nociplastic Pain Group ( Figure 1 ). In Phase 3, we compared CPS values in the Nociplastic Pain Group to a General Population Group and an Age- and Sex-Matched Group. These 3 phases are explained in more detail below. A detailed description of the CPS development has previously been published ( Schirle et al., 2023 ). Briefly, the weighting used to calculate the score was derived from a combination of previously published studies that have used the CSI Part A in a population of patients who have one of the targeted COPCs (listed below) and the categories of central sensitization established by the CSI authors ( Neblett et al., 2017 ). The CSI Part A is a validated measure of extent of central sensitization symptoms consisting of 25 items that capture the frequency of common central sensitization-related symptoms (0-never, 1-occasionally, 2-sometimes, 3-frequently, 4-always). It has a possible score ranging from 0–100 ( Mayer et al., 2012 ) and total scores are categorized based on prior work into subclinical (0–29), mild (30–39), moderate (40–49), severe (50–59) and extreme (>60) central sensitization ( Neblett et al., 2013 ). To minimize bias, only conditions with > 1 published study quantifying the CSI score within the particular COPC diagnosis were included in initial score development and mean scores across studies were weighted by study sample size. For example, two studies examined central sensitization burden in IBS patients using the CSI ( Falling et al., 2020 ; Neblett et al., 2013 ). The average CSI score among the two studies was 54.3, however one study had a significantly larger sample size (N=208 versus N=18). To mitigate bias due to disparate sample sizes, a CSI average weighted by sample size was performed, which resulted in an overall average CSI for IBS of 48.9, consistent with moderate central sensitization, based upon the categories established by Neblett and colleagues described above ( Neblett, et al., 2013 ). Using these categories, we then assigned severity weights for each COPC (range = 1–4), based upon these average CSI scores (1= mild, 2= moderate, 3= severe, and 4= extreme) ( Supplemental Table 2 ). Fourteen studies addressing 8 chronic pain conditions were included: fibromyalgia [FM], interstitial cystitis [ISC], temporal mandibular dysfunction pain [TMD], irritable bowel syndrome [IBS], tension-type and migraine headache [HA], chronic low back pain [cLBP], osteoarthritis [OA], and rheumatoid arthritis [RA]. While pain in the latter two conditions is not generally considered nociplastic, a growing body of evidence supports the presence of central sensitization in a significant subset of these populations that warrant investigation ( Nijs et al., 2021 ). We weighted each of the pain conditions above by the degree of central sensitization indicated by the average CSI scores in the published studies for that condition. Then, at the individual patient level, the weights associated with all COPC-related diagnoses recorded in the EHR for a given patient were summed. This procedure resulted in a single CPS value comprising the total of the weights for all COPCs present in a given patient record, thus quantifying central sensitization burden for each patient. Centralized Pain Scores have possible ranges from 0–14, with higher scores indicating higher central sensitization burden. We interpret a score of “3” to indicate severe central sensitization, as this is the score of fibromyalgia, a chronic pain condition considered the prototype of central sensitization ( Neblett et al., 2013 ). This study utilized data from a large academic medical center in the southern United States. The Synthetic Derivative (SD) - a multi-source database of de-identified clinical data derived from the clinical EHR was used. The SD duplicates the clinic EHR with removal of patient and provider names and other identifiers while otherwise maintaining semantic integrity. ( Roden et al., 2008 ). Data from the SD are not synthesized but represent an accurate reflection of clinical EHR data. Using the search function in the SD database, all clinical notes for 3,965,634 individuals were searched for the terms “centralized pain”, or “central sensitization”. A total of 6,431 individuals resulted. Notes were manually searched by Author 1, a nurse anesthetist and pain researcher, until 100 cases of clinically documented nociplastic pain were determined, representing a clinical ‘gold standard’ of nociplastic pain. To ensure this manual review identified confirmed cases where a clinician believed that nociplastic pain was a component of the patient’s pain, individual notes were searched for the terms “centralized pain” or “central sensitization”, or “nociplastic” or any variation of those terms within a note and where the text indicated a change in treatment approach based upon this determination. Individual records that met both of these criteria were selected for the Nociplastic Pain Group. Records were not included in the Nociplastic Pain Group if the clinician only documented they suspected or were ruling out nociplastic pain. Manual review ceased once 100 records were verified to document nociplastic pain. The Nociplastic Pain Group skewed highly female (83%) with a mean age of 53.63 years. To generate a Sex- and Age-Matched comparison group, an SD dataset from prior CPS research with genotyped data (no genetics were used for this study) was used ( Schirle et al., 2023 ). The full genotyped dataset of 55,340 individuals was used to represent a General Population Group. The MatchIt package version 4.6.0 in R version 4.4.2 was used to select a 1:5 nociplastic pain to age- and sex-matched comparison dataset using the nearest neighbor method ( Figure 1 ) ( Thoemmes & Kim, 2011 ; Zakrison et al., 2018 ). We used MatchIt to construct a matched dataset (Age- and Sex-Matched Group) close to the mean age (53.63) and sex distribution (83%F) of the Nociplastic Pain Group. To perform this the General Population dataset was loaded into R statistical program, and the MatchIt package estimated a distance measure (propensity score) for the variables of age and sex . To test the usefulness of the CPS as a proxy for nociplastic pain, CPS scores in the manually identified Nociplastic Pain Group (N=100) were compared to the larger General Population Group (N=55,340) and the Age-and Sex-Matched Group (N=500). During manual review, it was noted that an ICD code (ICD9–380.0 or ICD10-G89.0) or the term “central pain syndrome” that was originally intended for post-stroke or “thalamic pain” was being used to document nociplastic pain. Two authors performed a post-hoc content analysis on the clinical notes in the Nociplastic Pain Group to examine the various terminology used to describe nociplastic pain. Descriptive analysis of groups included mean (standard deviation) and median (interquartile range) for continuous variables and percentages for categorical variables. Independent sample t-tests were used to compare the mean CPS score for the manually identified Nociplastic Pain Group (N=100) to CPS values in the General Population Group (N=55,340) and the Age- and Sex-Matched Group (n=500). Distributions of the CPS score among the 3 groups and of sex-stratified COPC were visualized via bar charts. In the post-hoc content analyses, clinical notes from the 100 Nociplastic Pain Cases in which clinicians documented their determination that the patient has nociplastic pain, and treatment options that they have or will be implementing for this pain mechanism are copied into a spreadsheet and loaded into the online qualitative data analysis tool Dedoose (Version 9.0.107). Next, 2 clinical researchers (Author 1 and Author 2) independently reviewed language in the clinical notes to identify terminology used by clinicians to denote the nociplastic pain concept. Short (1–4 word) terms were selected from these notes and collapsed into codes. A deductive approach was used in which the researchers were instructed to identify common terms clinicians used to describe a centralized pain mechanism, and common changes to pain treatment clinicians described in response to this centralized pain determination ( Naeem et al., 2023 ). Using this process Author 1 and Author 2 independently coded the clinical note data. Pain terminology and treatment codes were then collapsed into categories, categories were compared, and any differences were resolved through consensus. No instances of disagreement occurred. A-priori power analysis was not possible in this EHR-based study because the distribution of the CPS values are not known in advance. Minimally statistically significant analyses indicated this study was powered to detect CPS differences between the 3 groups, and sex differences within the General Population Group.

The mean CPS score in the manually identified Nociplastic Pain Group was 3.7 [SD=2.9], significantly higher than the Sex- and Age-Matched Group (CPS mean 0.47, p<.001) and the General Population Group (CPS mean 0.43, p<.001) ( Table 1 ). Distribution of CPS values in Nociplastic Pain and Age- and Sex-Matched Groups are depicted in Figure 2 . In the Nociplastic Pain Group, 71% of individuals met the threshold for severe nociplastic pain (CPS≥3), whereas 5.8% of in those in the Age- and Sex-Matched Group had CPS values ≥3. Sex differences between groups were noted. Overall, there were more females than males in all groups. There was a significant difference in CPS values between females and males in the General Population Group (t= −35.52, p <.001) ( Table 2 ). Due to low sample sizes, we were unable to calculate sex difference significance in CPS scores in the Nociplastic Pain Group or the Sex- and Age-Matched Group. The most common pain condition in the Nociplastic Pain Cases was FM, with 60% of the Nociplastic Pain Cases containing a FM ICD code in both females and males, followed in frequency by cLBP (F 47%, M 59%) and HA (F 33%, M 35%) ( Figure 3 ). Males and females demonstrated generally similar distributions of pain conditions, although males had more cLBP ICD codes and females had more OA ICD codes. The most common term used by clinicians to describe nociplastic pain was central pain syndrome (35 notes), followed by central pain sensitization (26 notes), central sensitization (19 notes), central pain (14 notes), and centralized pain (8). Infrequent terms included central pain sensitivity (3 notes), centrally mediated pain (3), and central processing abnormality (1) ( Table 4 ). In the 100 Nociplastic Pain Group records, no clinicians used the IASP term “Nociplastic Pain”. Terms were often accompanied by the terms “features of”, “components of”, “elements of”. Overall, the most common treatments recommended by clinicians to address nociplastic pain were gabapentinoids (Gabapentin and pregabalin) (36 notes) and duloxetine (35 notes). Other recommended medications include a variety of antidepressants other than duloxetine (12 notes), and non-steroidal anti-inflammatory drugs (8 notes). Opioids were mentioned in 31 notes, most commonly to suggest weaning or to educate patients against use (23 notes), however 8 notes documented prescription renewal, often with stipulations such as signed opioid contract or limited supply. Non-pharmacological treatment recommendations were home exercise (26 notes), physical therapy (22 notes), acupuncture (11 notes), movement therapy such as yoga or tai chi (8 notes), and integrative medicine referral (8 notes). In 8 notes interventional pain management was mentioned, half of these recommended interventional procedures, and half recommended against them. In 30 notes, clinician documented patient education on chronic pain topics related to central sensitization in the form of consultation, videos, or group classes.

The purpose of this project was to develop and validate the CPS as a method to identify nociplastic pain in real world clinical data. Compared to the General Population Group and the Age-and Sex-Matched Group, the CPS was 8-fold higher in the Nociplastic Pain Group, a group representing real-world clinical use of the nociplastic pain concept. These findings, combined with our previous work which showed the CPS significantly correlates with polygenic risk scores for pain ( Schirle, et al., 2023 ), suggest the CPS has value as an EHR tool to investigate nociplastic pain. In the Nociplastic Pain Group, 17 individuals had a CPS score of 0. A review of these individual’s clinical notes demonstrated no ICD codes for the 8 COPCs included in the CPS, but a “central pain syndrome” ICD code (ICD9 338.0 or ICD10 89.0) was present in 13 of the 17 records. Central Pain Syndrome is a chronic pain condition resulting from damage or dysfunction within the central nervous system including the brain, brainstem, or the spinal cord ( NINDS, 2024 ). The Central Pain Syndrome diagnostic pain code was not intended to be used for nociplastic pain. A 2015 article published in the medical news site, MedCentral , advised clinicians that a clinical diagnosis of pain centralization should be made to fit into the current ICD9 and ICD10 codes, and instructed clinicians to use the central pain syndrome code to denote centralized pain, ( Force, 2015 ) despite the acknowledged differences between the original intent of the central pain syndrome ICD codes and pain resulting from central sensitization. The article states “Practitioners who wish to use terms for centralized pain not found in ICD9 and ICD10, such as neuropathic, intractable, thalamic, persistent, spontaneous, or sensitization, should attach the words central or centralized to their preferred term. For example, we suggest central neuropathic or central intractable pain”. This confusion of terms predates the IASP attempt to clarify the definition of pain terms and the inclusion of ‘nociplastic pain’ as a separate pain classification ( Nicholas et al., 2019 ). Further discussion regarding the central pain syndrome term is presented in the content analysis section below. Overall, 83% of the Nociplastic Pain Group were female, consistent with established beliefs that COPCs, central sensitization, and nociplastic pain are predominantly female conditions ( Clauw, 2024 ; Kaplan et al., 2024 ). Given that COPC diagnoses are more prevalent in females and the CPS was built on ICD codes for COPCs, this is not an unexpected finding. In the General Population Group, females demonstrated a significantly higher CPS value than males. However, this may represent the lower potential for males to receive certain COPC diagnoses and underreporting of nociplastic pain conditions generally (discussed in detail below). One surprising finding in this study was that although FM prevalence is considered much higher overall in females (70–96% female) ( Ruschak et al., 2023 ; Soroosh, 2024 ), FM was identified in equal proportions of females and males (60%) in the Nociplastic Pain Group. Differences have been described in symptomology between females and males with FM ( Ruschak et al., 2023 ). While females with FM report higher pain intensity than males, males report more severe impact and more catastrophic impressions of pain on their lives than females. It has been suggested that these differences in FM characteristics may in part due to resistance of clinicians to diagnosis FM in males until more pronounced symptoms are present. Researchers now believe FM is underdiagnosed in male populations due to overly strict previous diagnostic criteria and clinician gender bias ( Srinivasan et al., 2019 ; Wolfe & and Häuser, 2011 ) and have revised the estimated female to male ratio closer to 2:1 ( Wolfe et al., 2018 ). The equal proportion of FM between females and males in the Nociplastic Pain Group aligns with the premise that a smaller difference in FM prevalence exists between the sexes than previously understood. Finally, males only represented 17% of the Nociplastic Pain Group, therefore sex differences could not be examined statistically. However, interesting COPC patterns were noted. Overall, CPS values appear strongly driven by diagnoses of FM in both males and females in this sample. Fibromyalgia is considered the prototype of a nociplastic pain condition, but as indicated above, the equal proportion between the sexes was unexpected. In this study, similar patterns were identified for HA (which include both migraine and tension-type), with males having a higher proportion of ICDs than females despite HA being significantly more prevalent in general population than females ( Burch et al., 2018 ; Neumeier et al., 2021 ). In addition, a higher proportion of male records contained a diagnosis of RA than females despite an estimated prevalence of 3:1 for females to males in the general population ( Maranini et al., 2022 ). One potential hypothesis for the unexpected proportion of female to male prevalence in COPC diagnoses detected in this study may be the greater burden needed for a documentation of central pain for males due to clinician gender bias. This hypothesis requires larger studies powered to investigate sex differences. Clinician notes documented nociplastic pain using a variety of terms. The most common term was Central Pain Syndrome (often accompanied by the ICD9 code 338.0/ ICD10 code G89.0). As discussed above, central pain syndrome is a diagnostic code intended for use in post-stroke syndrome pain or thalamic pain. In our data sample, over 1/3 rd of the records included the term central pain syndrome to describe nociplastic pain cases. Of note, our Nociplastic Pain Group did not include individuals with conditions typical of central pain syndrome, such as traumatic brain injury, stroke, or other central nervous system damage. Despite this a substantial number of notes adopted the term ‘central pain syndrome’ to represent nociplastic pain. Examples of such notes include: 338.0 Central Pain Syndrome- Ms. XXX has multiple centrally mediated conditions including IBS, IC and fibromyalgia… I have counseled at length on chronic pain and a multi-modal approach to managing it, Diagnoses: Central pain syndrome, He has a significant history of trauma as a child which I believe significantly contributes to overall central sensitization, especially in the setting of other chronic illnesses. Given the pervasiveness of records utilizing the central pain syndrome term and ICD codes to document nociplastic pain, future CPS versions may consider sensitivity analyses of including the central pain syndrome ICD code. Although no records contained the recommended term nociplastic pain, the intent of the manual review was to create a dataset of 100 individuals manually adjudicated as having nociplastic pain with which to test the CPS score and did not use a randomized or exhaustive record search. 338.0 Central Pain Syndrome- Ms. XXX has multiple centrally mediated conditions including IBS, IC and fibromyalgia… I have counseled at length on chronic pain and a multi-modal approach to managing it, Diagnoses: Central pain syndrome, He has a significant history of trauma as a child which I believe significantly contributes to overall central sensitization, especially in the setting of other chronic illnesses. Several limitations limit the generalizability of study findings. All phases of the study were conducted in a single healthcare setting. We only analyze data that are documented in the EHR. Undocumented pain conditions or treatments were not analyzed, and no data imputation methods were used to attempt to fill in missing data. In addition, content analysis of clinical notes in the EHR focuses on clinician documentation only, and the deidentification process obscures important context such as clinic specialty, and no temporal exploration was performed. Terminology and ICD coding for COPCs and nociplastic pain may vary at other institutions. In addition, only 8 COPCs are included in the CPS. Future CPS updates may include additional COPCs as the literature evolves. Similarly, the CPS was created before publication of a suggested list of ICD10 codes to be used in COPC research ( Schrepf et al., 2020 ). Future CPS updates may also utilize the suggested ICD10 codes for these COPCs. Since the manual review identified cases by requiring clinician documentation of centralized pain and a therapeutic intervention targeting centralized pain, risk of bias in clinical note interpretation was minimized. However, risk of bias in interpretation of EHR data is always a consideration, and due to referrals from outside institutions, the date of initial determination of centralized pain may not be identifiable. Finally, the small number of males included in the Nociplastic Pain Group limited statistical power and prohibited analyses on comparisons of differences in the frequencies of COPCs by sex, and decreased generalizability of study results. Future studies with larger male cohorts will be necessary to investigate potential sex differences. Validation of the CPS is needed in external data sources. As more studies employing the CSI in other chronic pain conditions are published, we will update the CPS to include these conditions. We also plan to investigate using the Central Pain Syndrome ICD codes in future CPS analyses.

Clinicians are recognizing and documenting nociplastic pain in clinical notes and consequently altering treatment plans with interventions more effective for pain involving a centralized component (e.g. GABA-agonists, psychological therapies). The CPS appears to capture nociplastic pain, and while ICD codes for central-pain syndrome were not originally intended to capture nociplastic pain, this term and associated ICD codes are frequently used to describe central sensitization and centralized pain. Engaging a method to identify nociplastic pain in EHR data will accelerate use of large-scale examination of health trajectories of pain conditions as well as examination of genetic underpinnings of nociplastic pain through use of genetic biorepositories linked to EHR data, with the ultimate goal of improving diagnosis and treatment of nociplastic pain. Implications for nursing: The CPS is a tool that can assist nurse scientists with large-scale exploration of nociplastic pain in EHRs and biorepositories. Findings from this study inform nurses about potential central sensitization burden associated with common chronic pain conditions. Nurses are apprised of common terminology that may alert to the presence of nociplastic pain and may require altered analgesic plans. The CPS is a tool that can assist nurse scientists with large-scale exploration of nociplastic pain in EHRs and biorepositories. Findings from this study inform nurses about potential central sensitization burden associated with common chronic pain conditions. Nurses are apprised of common terminology that may alert to the presence of nociplastic pain and may require altered analgesic plans.

Nociplastic pain, a third type of pain mechanistically different from nociceptive or neuropathic pain, presents with amplified pain symptoms including hyperalgesia, allodynia, and widespread pain non-responsive to standard peripherally-focused pain therapies ( Clauw, 2024 ).The term ‘nociplastic pain’ was adopted by the International Association for the Study of Pain (IASP) in 2017, defining it as “pain that arises from altered nociception not fully explained by nociceptive or neuropathic pain mechanisms” ( Kosek et al., 2016 ). Prior to this, several terms were used to describe the nociplastic pain phenomena including ‘centralized pain’, ‘central sensitivity syndrome’, ‘functional pain syndrome’ and ‘chronic overlapping pain conditions’ (COPCs) ( Kaplan et al., 2024 ). This last term describes a group of chronic pain conditions for which nociplastic pain is thought to be the predominant pain mechanism, leading some researchers to recommend use of the term “Nociplastic Pain Syndromes” ( Rodríguez-Palma et al., 2024 ). Chronic Overlapping Pain Conditions include, but are not limited to, fibromyalgia (FM), irritable bowel syndrome (IBS), temporal mandibular disorders (TMD), urological chronic pelvic pain syndrome (CPP), myalgic encephalomyelitis/chronic fatigue syndrome (CFS), vulvodynia, painful endometriosis (EM), migraine and tension-type headache [HA], and chronic low back pain (cLBP) and co-occur at a rate higher than expected by individual disease prevalence ( Maixner et al., 2016 ; Schrepf et al., 2024 ). Individuals who develop COPCs often display a pattern of central sensitization symptoms early in life (i.e. pain amplification, fatigue, sleep disturbance, sensory sensitivity) with co-occurring or sequential development of additional chronic painful conditions ( Aaron & Buchwald, 2001 ; Harte et al., 2018 ) leading to the hypothesis that COPCs represent a single lifelong disease that manifests in different body regions over time. ( Williams & Clauw, 2009 ; Woolf, 2011 ) Not everyone with a COPC exhibits central sensitization symptoms, but as the number of COPCs within an individual increases, the likelihood of central sensitization and nociplastic pain increases ( Maixner et al., 2016 ) and is associated with worse pain, psychosocial, and functional outcomes, suggesting a common underlying causal mechanism. ( Barad et al., 2021 ; Bartley et al., 2024 ; Boggero et al., 2024 ; Fall et al., 2024 ; Justribó-Manion et al., 2024 ; Ohrbach et al., 2020 ; Till et al., 2022 ; Zheng et al., 2024 ) Central sensitization, an amplification of neural signaling within the central nervous system (CNS) that elicits hypersensitivity ( Woolf, 2011 ), is believed to be at least partially responsible for the amplified pain (i.e. nociplastic pain) and other CNS symptoms inherent in COPCs ( Clauw, 2024 ; Fitzcharles et al., 2021 ; Harte et al., 2018 ). Central sensitization is now recognized as an important underlying mechanism of neuropathic and nociplastic chronic pain types ( Nijs et al., 2021 ). In essence, COPCs are chronic pain states that are believed to have a common underlying mechanism of sensitization of the CNS (central sensitization), leading to nociplastic pain. Although no single gold standard exists to identify central sensitization ( Nijs et al., 2023 ), several measures exist to quantify it including objective quantitative sensory testing (QST) and subjective patient report tools such as the Central Sensitization Inventory (CSI) and Pain Sensitivity Questionnaire (PSQ) ( Adams et al., 2022 ). Electronic health records (EHR) hold significant value in pain research, providing rich, longitudinal, real-world clinical data for large-scale investigations of pain trajectories, treatment effectiveness, identification of pain phenotypes and endophenotypes, and genomic exploration ( Tang et al., 2024 ). A requirement of EHR research is the availability of a data point to capture the concept of interest, which often involves the presence of a diagnostic code ( Gianfrancesco & Goldstein, 2021 ). Currently there is no diagnostic code for nociplastic pain, which hampers large-scale clinical research. However, International Classification of Diseases (ICD) codes do exist for COPCs. The purpose of this study was to develop and validate the Centralized Pain Score (CPS) as a method to identify nociplastic pain in EHRs by comparing CPS values across a clinically determined Nociplastic Pain Group, an Age- and Sex-Matched Group, and a General Population Group. We developed the Centralized Pain Score (CPS) using ICD codes for COPCs weighted by the degree of central sensitization for each of these pain conditions identified through previous research. ( Schirle, et al., 2023 ). A total of 76 ICD9, and 204 ICD10 codes were used in the development of the CPS score ( Supplemental Table 1 ). We have previously reported genomic correlation between the CPS and other pain phenotypes ( Schirle, et al., 2023 ). Of note, we have chosen the Centralized Pain Score title because it is built from COPC scores weighted by the degree of central sensitization as measured by the Central Sensitization Inventory, a term that predated the adoption of nociplastic pain term. Throughout this manuscript we will use the modern term, nociplastic pain, to denote amplified pain associated with central sensitization. Similar to the lack of diagnostic codes to identify a nociplastic pain condition, there are currently no accepted gold standard to identify individuals with nociplastic pain ( Irwin & Smith, 2022 ). Although the IASP has suggested several clinical criteria to classify nociplastic pain (i.e. pain ≥ 3 months duration, regional pain distribution, pain not explained by nociceptive or neuropathic mechanisms, and pain hypersensitivity) ( Kosek et al., 2021 ), these criteria may not be readily present in EHR data. Given this limitation, we have chosen to use documentation of a central component to the patient’s pain in clinical notes and documentation of a recommended change in treatment based upon this judgement, representing real-world clinical use of the nociplastic pain concept as a “gold standard”. The CPS aligns with clinical criteria for the determination of nociplastic pain ( Kosek et al., 2021 ) through the use of chronic pain ICD codes (indicating pain > 3 months), and the CSI (items rating hypersensitivity and comorbidities of sleep disturbance, fatigue, and cognitive problems) ( Mayer et al., 2012 ). The use of EHR data to study nociplastic pain will allow large-scale examination of health trajectories of nociplastic pain conditions which can help clinicians pinpoint early markers of nociplastic pain development, evaluate pain management response in subgroups of patients experiencing chronic nociplastic pain, as well as examination of genetic underpinnings of nociplastic pain through use of genetic biorepositories linked to EHR data. Institutional Review Board approval was obtained for this study.