Frontiers in Pain Research

BackgroundHigh-frequency repetitive transcranial magnetic stimulation (rTMS) has been reported to yield promising, albeit variable, outcomes in chronic pain therapy and management. A factor contributing to the treatment success is individual neuroplastic capacity. Neuroplasticity can be assessed in various ways with TMS, e.g. through neural repetition suppression (RS) based on habituation. The present study aimed to evaluate the TMS-induced RS in patients with chronic pain, undergoing conventional rTMS treatment, and observing whether RS is indicative of the experienced analgesic effects. MethodsTwenty-one patients received standard 10-Hz rTMS treatment in five or ten daily sessions. Twenty RS trials, each consisting of four TMS pulses given 1 s apart, were given and assessed for motor evoked potentials (MEPs) before the first rTMS therapy session. For analysis purpose, the RS paradigm was evaluated through two states: 1) "dynamic" state (spontaneous excitability), first to second pulse, and 2) "stable" state (suppressed excitability), suppressed responses induced by second to fourth pulse. Analgesic effect from rTMS was assessed using Brief Pain Inventory (BPI), and painDETECT screening questionnaire, both conducted before and after the rTMS treatment. ResultsBoth the dynamic and the stable state RS exhibited good accuracy (0.789 - 0.944) in identifying patients showing analgesic effect in response to rTMS. Also, significantly greater suppression of MEPs (p<0.05) were observed in the RS between those who benefitted from rTMS and those who did not. ConclusionsThese indicative findings provide support for the potential of RS to set a premise for improved individualized neuromodulation treatments.

ObjectiveInadequate pain control during early zoster-associated pain (ZAP) can lead to postherpetic neuralgia (PHN), and traditional treatments have limitations. This retrospective analysis compares the analgesic effects of burst (BurstSCS) versus traditional tonic (TonicSCS) spinal cord stimulation in early ZAP patients, using retrospective data. It also evaluates differences in psychological state and sleep quality. The findings offer insights into the multidimensional effects of these SCS modalities for future research. MethodsRetrospective analysis included 40 consecutive early ZAP patients undergoing SCS trial (From March 1, 2023 to March 1, 2025). Groups: BurstSCS (n=20) vs. TonicSCS (n=20) based on documented treatment selection. Outcomes assessed at baseline, 14, and 30 days: visual analog scale (VAS), Pittsburgh Sleep Quality Index (PSQI), Pain Vigilance and Awareness Questionnaire (PVAQ). Intergroup comparisons used independent t-tests (significant at P<0.05). ResultsAt 14 days, BurstSCS achieved greater pain reduction (VAS: 1.95 {+/-} 0.76 vs 2.65 {+/-} 0.75; *P*=0.006) and better secondary outcomes:PSQI: 7.00 {+/-} 2.08 vs 8.90 {+/-} 1.89,PVAQ: 15.55 {+/-} 2.80 vs 22.20{+/-}2.42,(all *P*<0.05). At 30 days, VAS was comparable (1.40{+/-}1.23 vs 1.80{+/-}0.95) but BurstSCS maintained lower PSQI (4.90{+/-}1.33 vs 5.85{+/-}1.60) and PVAQ (9.00{+/-}1.56 vs 18.50{+/-}2.16) (*P*<0.05). ConclusionsBurstSCS provided superior early pain reduction (>70% VAS decrease at 14 days) and sustained improvements in sleep quality and pain vigilance in early ZAP patients. These findings support its potential for multidimensional symptom management, warranting validation through prospective trials. KEYWORDS:Spinal cord stimulation; Neuralgia, Postherpetic; Retrospective studies; Pain management.

Background and aimsChronic pain is a major part of the disease burden in Charcot-Marie-Tooth (CMT) disease. Current pharmacotherapies to manage symptoms of CMT disease, particularly pain, are inadequate. This exploratory study examined the patient reported efficacy of medical cannabis among CMT patients. MethodsParticipants (N = 56; 71.4% female; Age = 48.9, SD = 14.6; 48.5% CMT1) were recruited though the Hereditary Neuropathy Foundations Global Registry for Inherited Neuropathies. The online survey contained 52 multiple choice questions about demographics, medical cannabis use, symptomology, efficacy, and adverse effects. ResultsWhen asked about how much relief they experience from using cannabis as a method of symptom relief, respondents reported an average of 69.6% (SEM + 2.6). Women were more likely to report experiencing pain than men (p < .05). Participants who perceived support from their providers were more likely to inform them of their cannabis use (p < .05). InterpretationPatients reported that cannabis was effective to manage symptoms. More prospective and controlled research needs to be conducted to better serve and optimize the potential use of cannabis to treat CMT. Graphical AbstractPatient Reported Outcomes of Medical Cannabis for Managing Pain in Patients with Charcot-Marie-Tooth Disease Priscilla C. Canals, Alexia G. Aguilar, Gregory T. Carter, Marion McNabb, Andrew M. Westerkamp, Miyabe Shields, Meg DElia, Joy Aldrich, Robert N. Moore, Allison T. Moore, Brian J. Piper* O_LIThere is no prior research of medical cannabis experiences among Charcot-Marie-Tooth (CMT) patients. C_LIO_LICMT patients (N=56) were recruited though the Hereditary Neuropathy Foundations Global Registry for Inherited Neuropathies and completed an online survey. C_LIO_LISymptom relief from using cannabis was moderately-high (70% + 3). C_LIO_LICMT patients that received support from their providers were significantly more likely to inform them of their cannabis use. C_LIO_LIThese descriptive results should be verified using prospective and randomized controlled trials. C_LI O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/22278591v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@108bafcorg.highwire.dtl.DTLVardef@2c0e83org.highwire.dtl.DTLVardef@6ceedcorg.highwire.dtl.DTLVardef@1b5d9d8_HPS_FORMAT_FIGEXP M_FIG C_FIG

IntroductionChronic pain is the most common qualifying condition found in states with medical cannabis (MC). We conducted a study assessing the geographic distribution of MC certifications for severe chronic or intractable pain in Pennsylvania (PA) between 2018 to 2024, identifying relationships between median household income and ethnic background with the percentage of adults with a MC certification for pain. MethodsUsing data from the PA Department of Health (PDOH) from 2018 to 2024 (N = 44,645 to 165,740 certifications for pain / year), we mapped Zip codes associated with MC certifications for pain to counties and Zip code tabulation areas (ZCTAs). The difference between the highest and lowest counties was determined. A linear regression evaluated correlations between community variables and the percentage of adults in geographical areas with a MC certification for pain in 2024. ResultsThere was an almost a four-fold difference in the percent of adults with a MC certification for pain in the highest (Perry = 2.3%) versus lowest (Tioga = 0.6%) counties in 2024. Bradford and Tioga County had a significantly (p < 0.05) lower percentage certified relative to the county-wide average. There was a significantly higher proportion of certifications for pain in counties with larger population densities of adults (1.76 +/- 0.12%) than counties with smaller population densities (1.38% +/- 0.14%) of adults (t(65) = 4.66, p < 0.001, d = 1.14). At the county level, higher median household income was associated with a greater percentage of adults with MC (r(65) = +0.34, p < 0.01). At the ZCTA level, the proportion of non-White individuals, including Hispanics, showed a modest, but significant, inverse association with MC certification (r(1,722) = -0.07, p < 0.01). ConclusionsThis study identified four-fold county level disparities in MC certifications for pain. The association between median household income and MC pain certifications may indicate differences in accessibility of MC based on financial status. Further research may be warranted pending any changes to the legal status or demand for MC.

Evidence for the objective clinical evaluation of scar hyperesthesia is lacking. This exploratory study investigated the clinical relevance and responsiveness of objective scar evaluation measures in adults following hand surgery. With ethical approval and consent, participants were enrolled from one NHS hospital. Patient reported and investigator completed scar morphology, cosmesis, pain and function were evaluated at 1- and 4-months post-surgery. Statistical analysis investigated the responsiveness of outcome measures and association of physical measures with the Palmar Pain Severity Scale (PPS). 21 participants enrolled prior to premature study closure due to the COVID-19 pandemic; 13 completed follow up. Scar pain (p=.002); scar interference (PPI [p=.009]) and Brief Pain Inventory (BPI) scores (p=.03) improved. Neuropathic Pain Symptom Inventory (NPSI) scores demonstrated heterogeneity in scar pain; evoked pain predominated. Patient Scar Assessment Questionnaire (PSAQ) indicated improvement in cosmetic dissatisfaction and consciousness (p=.03; p=.003), respectively. Baseline psychological screening scores correlated with scar pain (p=.04), and interference (p< .001). Scar morphology, pliability and inflammation were not associated with scar pain. Significant differences in scar mechanical pain sensitivity (p=.04) and cold pain threshold (p=.05) were identified. PPS and PPI scores were responsive in a heterogeneous hand surgery sample. BPI worst pain identified severe pain, suggesting composite scar pain scores are required. The PSAQ robustly measured scar appearance and consciousness. Psychophysical tests of mechanical and thermal sensitivity are potential candidate objective measures of scar hyperesthesia. The NPSI demonstrates clinical utility for exploring scar pain symptoms and may support the elucidation of the drivers of persistent scar pain.

BackgroundFibromyalgia is a chronic pain disorder, affecting 2-3% of the population, characterised by widespread pain, fatigue, sleep and cognitive symptoms. Despite symptom overlap between functional motor disorder (FMD) and fibromyalgia, the prevalence of fibromyalgia in FMD and its impact on health-related quality of life (HRQoL) remain unclear. ObjectivesTo assess the prevalence of fibromyalgia in FMD using the 2016 American College of Rheumatology diagnostic criteria and to evaluate its impact on HRQoL. MethodsA total of 139 consecutive patients with clinically established FMD (115 females, mean age 44.6 (SD 11.3) years) completed Fibromyalgia Survey Questionnaire, subjective motor symptoms and HRQoL assessments. Motor symptoms were objectively rated using the Simplified FMD Rating Scale (S-FMDRS). Major physical illnesses, neurological, and psychiatric comorbidities, and the use of centrally acting and nociceptive pain medication was recorded. ResultsFibromyalgia was present in 44.6% of FMD patients (95%CI: 36.2-53.3%). Those with fibromyalgia had higher S-FMDRS scores (p < 0.01), lower HRQoL (p < 0.001), more frequent use of centrally acting and nociceptive pain medication (p < 0.01). Fibromyalgia severity was positively correlated with both subjective motor symptom severity (p < 0.01) and S-FMDRS (p < 0.05). Higher fibromyalgia severity (p < 0.001), S-FMDRS (p < 0.001), and psychiatric comorbidity (p < 0.001) were independent predictors of lower HRQoL. ConclusionsIn this study, fibromyalgia was common in FMD and associated with more severe motor symptoms, greater medication use and reduced quality of life, highlighting the importance of recognising and managing fibromyalgia in FMD.

BackgroundChronic pain is usually refractory to treatment. Ketamine is often used to treat chronic refractory pain.In France most of the patients are treated in pain units day hospital. This study aims to evaluate the effectiveness of continuous four days of Ketamine infusion associated with magnesium sulfate for inpatients. MethodsA total of 89 patients received a 4 days continuous subanesthetic IV ketamine infusion associated with 1000 mg/day of magnesium sulfate.Primary outcome was mean pain intensity (Numerical Rating Pain Scale) 30 days after infusion. Patient Impression of Change (PGIC), Anxiety and depression (HADS), Neuropathic Pain (NPSI), quality of life (SF-12) were secondary outcomes. ResultsKetamine continuous infusion was associed with decrease of NRS (7.54 {+/-} 1.35 at d0 to 5.59 {+/-} 2.2 at d30 [26%; p < 0.001]).The PGIC improved in 68.7 % patients (36.2 % reports "much improved" or "very much improved").There was a significant decrease of Npsi total score (-28% ; p < 0.0001) and an increase of SF12 (Mental health dimension from 31.4 {+/-}7.9 to 36.4 {+/-} 8.9 [+15.9 % ; p < 0.0001]; Physical health dimension from 30.2 {+/-} 6.7 to 32.8 {+/-} 6.8 [+8.6% ; p:0.0007]).The mean HADS Depression decreased from 10 {+/-} 4.5 at d0 to 8.2 {+/-} 4.6 at d30 (-15% ; p:0.0012) ; The mean HADS Anxiety decreased from 11.35 {+/-} 4.7 at d0 to 9.38 {+/-} 4.5 at d30 (-14% ; p < 0.0001). Conclusions Findings suggests that continuous low-dose infusion of ketamine is effective for chronic pain relief to inpatients.

The concept nociplastic pain has been developed for patients in whom clinical and psychophysical findings suggest a predominant central sensitization type of pain that is not fully explained as nociceptive or neuropathic. Here we tested, how well the recently published grading system differentiates between chronic primary pain or chronic secondary pain conditions. We recruited patients with Fibromyalgia (FMS, 41), Complex Regional Pain Syndrome (CRPS, 11), Osteoarthritis (OA, 21) or Peripheral Nerve Injury (PNI, 8). We used clinical history, pain drawings, Quantitative Sensory Testing (QST) and questionnaires to classify patients pains as possibly or probably nociplastic in nature. All FMS and CRPS patients exhibited widespread or regional pain that was not explainable by nociceptive nor neuropathic mechanisms. Widespread pain in 12 OA patients was fully explained as nociceptive and regional pain in 4 PNI patients as neuropathic in all but one in each group. QST provided evidence for hypersensitivity in 9/11 CRPS patients but only 27/41 FMS patients (possible nociplastic pain). 82% of the CRPS patients but only 54% of FMS patients reported a history of hypersensitivity and mental comorbidities (probable nociplastic pain). We suggest that clinical examination of hypersensitivity should be done in more than one region and that adding a high tender point count as evidence for hypersensitivity phenomena may be useful. Further we suggest to switch the sequence of steps so that self-reported hypersensitivity and comorbidities come before clinical examination of hypersensitivity; Since the nociplastic pain concept calls for brainstem and cortical plasticity we discuss in detail potential measurement strategies.

ObjectiveTo estimate the magnitude of the placebo and nocebo responses in chronic peripheral neuropathic pain (CNP) and explore possible associations with trial characteristics. MethodsWe searched CENTRAL, MEDLINE, and Embase for randomized controlled trials (RCTs) from inception to May 2020. We included placebo-controlled RCTs of [&ge;]8 weeks investigating first-line pharmacological interventions for CNP. Primary endpoints were the placebo response, the proportion of patients receiving placebo with pain intensity reduction (PIR) [&ge;]30% from baseline, and the nocebo response, the proportion of patients receiving placebo experiencing adverse events (AEs). Screening, data extraction, and bias assessment (with the Cochrane risk of bias tool) were conducted by independent reviewers. We pooled data using a random-effects model. ResultsWe included 50 trials, with a combined 5,693 participants allocated to placebo, conducted between 1998 and 2020. Overall, 38% of patients receiving placebo reported PIR[&ge;]30% (95% CI 34 to 42, I2=86%); 23% reported PIR[&ge;]50% (95% CI 20 to 26; I2=81%). 50% of patients receiving placebo reported AEs (95% CI 0.43 to 0.58; I2=97%); 2% reported serious AEs (95% CI 2 to 3; I2=58%). In patients receiving active interventions, the placebo response accounts for 75% of the treatment effect on PIR[&ge;]30%, and the nocebo response accounts for 75% of the AEs. Interpreted inversely, only 25% of responses and 25% of adverse events can be attributed to the intervention. Publication year positively correlated with PIR[&ge;]30% and negatively correlated with AEs. Female sex negatively correlated with AEs. ConclusionsThe placebo and nocebo responses in parallel-designed RCTs in CNP are substantial and should be considered in trial interpretation and in the design of future trials.

AimWe investigated the heterogeneity of treatment effects in transcranial direct current stimulation (tDCS) with mindfulness-based meditation (MBM) and within each individual study group (tDCS alone, MBM alone, and sham) among individuals with symptomatic knee osteoarthritis. We also explored participant characteristics underlying this heterogeneity. MethodsThis secondary analysis drew on a double-blind, randomized, sham-controlled, phase II, parallel-group trial in which 200 participants were assigned to one of four groups: (1) active tDCS + active MBM, (2) active tDCS + sham MBM, (3) sham tDCS + active MBM, or (4) sham tDCS + sham MBM. Participants received ten 20-minute tDCS sessions (active or sham) administered concurrently with MBM (active or sham). Latent class growth analysis was used to identify subgroups with distinct treatment response trajectories (responders vs. non-responders) based on changes in clinical pain (Numeric Rating Scale) from baseline to post-intervention. Generalized linear models were then applied to determine baseline factors associated with participants response classification, including demographic, clinical, and psychological characteristics; quantitative sensory testing battery; and pain-related cortical hemodynamic activity measured using functional near-infrared spectroscopy (fNIRS) in response to punctate and thermal stimuli. ResultsResponders in the active tDCS + active MBM and active tDCS + sham MBM groups demonstrated greater improvements in clinical pain from baseline to post-intervention than non-responders (p < 0.001). In the active tDCS + active MBM group, greater cortical activation in the fNIRS channel S06-D06 of the left somatosensory cortex in response to punctate stimuli, identifying as white, and lower conditioned pain modulation (reflecting less efficient endogenous pain modulation), were significantly associated with being responders (p < 0.05). In the active tDCS + sham MBM group, younger age and lower heat pain tolerance at the knee were significantly associated with being responders (p < 0.05). No clear response patterns were observed in the remaining groups. ConclusionFactors underlying heterogeneity of treatment effects, including somatosensory cortical activation and pain modulatory profiles, may provide preliminary insights to inform the development of personalized neuromodulation (stimulation) protocols.

IntroductionDespite limited scientific evidence, trigeminal nerve blocks are alternative therapies for refractory trigeminal neuralgia (RTN). The duration of analgesia far exceeds the length of the conduction block. This study evaluated the quality of life 15 days after performing this block to treat RTN. MethodsThis retrospective study included all patients who, after informed consent, received iterative trigeminal blocks to treat a RTN between 2014 and 2018 in a university hospital. Patients received 0.5% levobupivacaine in combination with clonidine and a corticosteroid (cortivazol or betamethasone according their availability). Data were obtained from patients medical data files and a telephone questionnaire for the SF-12 score. The main criteria of evaluation was the change in quality of life according SF-12 performed at day 15. ResultsTwenty-one patients aged 62 {+/-}14 years were included. All patients exhibited RTN after many different clinical treatments according ICHD-3 criteria. Seventy-one per cent of RTN occurred after trauma or surgery. Before receiving blocks, SF-12 physical (SF12-PS) and mental (SF-12 MS) scores reached respectively 35 {+/-} 14 and 29 {+/-} 11. A mean time of 4 {+/-} 5 years elapsed between the occurrence of RTN and nerve blockade. At day 15, SF-12 PS increased by a 3 point mean value and SF-12 MS by 5 points. Approximately half of the patients (55%) were considered as non-responders with a cut-off value of less than 10% variation of their initial SF-12 score. When excluding these patients, SF-12 PS and SF-12 MS were increased by 17 and 9 points respectively. The mean duration of blocks lasted 15 {+/-} 59 days and no severe adverse effects were observed. Patient satisfaction was correlated with increased SF-12 PS (r2 = 0.3 p = 0.01) and with the length of analgesia (r2 = 0.51 p = 0.001) but not to SF-12 MS variation (p = 0.12). ConclusionTrigeminal nerve blocks are temporarily effective on pain that may increase the quality of life in responder patients. The reason why some patients are unresponsive to this treatment and why durations in efficacy are so variable remain unsolved. However, in responders, trigeminal nerve blocks seem simple, harmless, not excessively cumbersome and without severe adverse effects.

Chronic pain is prevalent among U.S. military personnel and often accompanied by comorbid behavioral health disorders and other medical conditions that further complicate its management. According to the Centers for Disease Control and Prevention, the prevalence of chronic pain among active-duty Service members is 1.5 to 2 times higher than the 20% of American adults who live with chronic pain. Recent report findings determined that Service members make up a large population within the Military Health Systems (MHS), and that this population is disproportionately affected by lost duty days, early retirement, loss of readiness, and increased burden to the MHS. To date, the Department of Defense (DOD) and MHS have emphasized multimodal, multidisciplinary, stepped treatment for chronic pain that prioritizes nonpharmacologic therapies and non- opioid pain medications. Though the DOD and MHS have invested in several pain treatment types, our level of understanding needs to better distinguish between acute and chronic pain and identify risk factors and mechanisms responsible for the chronification of pain, as it is the chronic pain which compromises functioning and readiness to a greater degree across the force. The novel information generated by this study will enhance our understanding of how ankle fracture elicits pathological risk factors for bone fracture associated neuropathic pain (BFNP), which ultimately impairs health-related quality of life. Due to the high prevalence of ankle fractures and the subsequent risk of developing chronic pain after ankle fracture, we will utilize this patient population to provide the preliminary evidence on whether bone fracture and subsequent BFNP phenotypes are reflected in specific genetic profiles and activated states of immune cells.

AbstractO_ST_ABSBackgroundC_ST_ABSReferred sensation (RS) is described as the sensation evoked in the skin areas other than the stimulated region. The aim of the study was to identify and map RS in traumatic brachial plexus injury (TBPI) patients through a standardised assessment. MethodsIn Experiment 1, 12 patients underwent an RS screening by stimulating 22 skin areas distributed in both upper limbs, neck, and face with a cotton swab. In Experiment 2, a detailed RS mapping employing Semmes-Weinstein monofilament was performed at the reinnervated forearm of three subjects who showed RS in experiment 1 screening. In one of these patients, RS mapping was performed over a time span of 6.3 years. ResultsScreening of TBPI patients submitted to different reconstructive surgeries revealed RS only in the patients who underwent intercostal to musculocutaneous nerve (ICN-MCN) transfer. RS systematic mapping of these patients revealed a unique distribution in the forearm and the chest, without any clear topographic organisation. Longitudinal assessment in one of the tested participants showed a scattered expansion of the RS throughout time. ConclusionsThis is the first study to map systematically the RS in patients with TBPI. RS was identified only after ICN-MCN transfer. A possible explanation for this phenomenon is that the greater distance between the representations of the donor and receptor nerves at the primary somatosensory cortex (S1) could constrain plastic reorganisation and thus limit the disentangling of the forearm and chest sensations.

A critical aspect for much human pain research is the ability of participants to communicate their first person, experiential perspective to a third person observer. This communication is frequently accomplished via pain ratings. The type of scale and how participants/patients may differentially use the scale has a major influence on the communication of pain experiences. The present study examined the role of sex on the pain rating process using both noxious and innocuous stimuli and two different types of rating scales. Participants underwent noxious heat, auditory and visual stimulation paradigms. Pain intensity and unpleasantness ratings were collected using the visual analog scale (VAS) and numerical rating scale (NRS) in a random order. For noxious heat stimuli, low (44-45{degrees}C) and high (47-48{degrees}C) intensity stimuli were delivered. To identify if one rating scale allows better discrimination between different stimulus intensities and if this is dependent on sex, discrimination thresholds were calculated. Significant effect for rating scale and intensity level of stimuli were found for all stimulus modalities (noxious heat, auditory and visual) indicating that higher intensity and unpleasantness ratings were found using the NRS compared to the VAS. No effect of sex or interaction with sex was found. No differences in rating scale and sex were found for the discrimination thresholds. Biases in rating scales usage exist with NRS yielding higher ratings to the same stimuli. However, this bias does not appear to contribute significantly to sex differences in pain.

Quantitative sensory testing (QST) is a psychophysical test of sensory function which may assist in assessing neuropathic pain (NP). This study compares QST findings with a standardized NP questionnaire to assess their agreement among Jamaicans with sickle cell disease (SCD). A cross sectional study consecutively recruited SCD patients 14 years and older, not pregnant, and without history of clinical stroke or acute illness in Kingston, Jamaica. QST identified thresholds for cold detection, heat detection, heat pain and pressure pain at the dominant thenar eminence, opposite dorsolateral foot and the subjects most frequent pain site. The Douleur Neuropathique 4 (DN4) was interviewer-administered to diagnose NP. Subjects were divided into low and high sensitization groups if below the 5th and above the 95th percentiles, respectively on QST measures. Kappa agreement coefficients, and receiver operator characteristic (ROC) curves were performed to compare QST with the DN4. Two-hundred and fifty-seven SCD subjects were recruited (mean age 31.7 {+/-} 12.2 years, 55.7% female, 75% SS genotype). Kappa agreements were fair (0.2-0.4) to good (0.6-0.8) between DN4 individual items of itching, hypoesthesia to touch, hypoesthesia to pinprick and brush allodynia with various QST sensitization groups. However, kappa agreements between the NP overall diagnosis on the DN4 with sensitization groups were poor (<0.2). Only heat detection (0.75) and heat pain (0.75) at the leg as a pain site showed satisfactory area under the curve (>0.7). QST may assist in assessing individual components of NP but its use should be limited as a tool to augment clinical assessments.

Neuropathic pain is one of the most common secondary complications occurring after spinal cord injury (SCI), and often surpasses motor and sensory deficits in the patient population preferences of the most important aspects to be treated. Despite the better understanding of the molecular and physiological mechanisms of neuropathic pain, reliable treatments are still lacking and exhibit wide variations in efficiency. Previous reports have suggested that the most effective pain management is early treatment. To this end, we utilized the TRACK-SCI prospective clinical research database to assess the neuropathic pain status of all enrolled patients and identify acute care variables that can predict the development of neuropathic pain 6- and 12-months post SCI. 36 out of 61 patients of our study cohort reported neuropathic pain at the chronic stages post SCI. Using multidimensional analytics and logistic regression we discovered that (1) the number of total injuries the patient sustained, (2) the injury severity score (ISS), (3) the lower limb total motor score, and (4) the sensory pin prick total score together predict the development of chronic neuropathic pain after SCI. The balanced accuracy of the corresponding logistic regression model is 74.3%, and repeated 5-fold cross validation showed an AUC of 0.708. Our study suggests a crucial role of polytrauma in chronic pain development after SCI and offers a predictive model using variables routinely collected at every hospital setting.

IntroductionOpiate misuse is increasingly common and can result from a single opiate exposure. High pain catastrophizing scores have been linked with greater reported pain and increased opiate use in outpatient studies, but this association has not previously been established in a perioperative setting. MethodsA quantitative, cross-sectional pilot study was conducted on 21 patients undergoing total knee arthroplasty surgery. Pain Catastrophizing Scale (PCS) scores and patients ASA Physical Status classifications were collected prior to surgery. Postoperative pain scores were measured using an 11-point numeric rating scale (NRS) and postoperative opiate consumption was measured using modified morphine equivalents (MMEs). Data were analyzed using Spearman rank correlation coefficients. ResultsSignificant correlations were found between NRS pain scores at 6 hours post-surgery and 48 hours post-surgery (.455); and NRS pain scores at 6 hours post-surgery and opiate consumption within the first 24 hours post-surgery (.591). A significant correlation was also found between ASA Physical Status classification and total opiate consumption (.522). While rumination scores within the Pain Catastrophizing Scale were also moderately positively correlated with reported pain scores 12 hours post-surgery (.41) and morphine dosing at 48 hours (.40), they were not significant. ConclusionsEarly preemptive pain management is an important component of overall postoperative pain management and to reduce opiate use. Results support that the ASA Physical Status classification scores may be helpful in identifying patients at risk for high opiate use. For the PCS, more data are needed to determine the clinical usefulness of the PCS as an adjunct to overall postoperative pain management.

ObjectiveTo create a questionnaire that can identify patients who will respond well to high-frequency spinal cord stimulation. Materials and MethodsThirty-three patients who received permanent implantation of a high-frequency spinal cord stimulator were followed for up to one year. Preoperative patient data in the form of a packet containing pain metrics, the Douleur Neuropathique 4 (DN4) questionnaire, and a questionnaire thought to contain clinically useful questions were collected. Visual analog scale (VAS), Oswestry Disability Index (ODI), and subjective overall percent pain reduction were collected at time points of 6 weeks, 3 months, 6 months, and 12 months. ResultsPatients who revealed that they could walk before a long period of time before their pain worsened, whose pain was consistent throughout the day, whose pain wakes them up from sleep and whose pain is worse when leaning side to side had a significant increase in ODI following SCS. Additionally, patients who reported only being able to sit or lie down for less than thirty minutes before having to move experienced significantly decreased ODI. ConclusionsWhile literature has shown that patients with neuropathic pain respond to SCS, identifying which patients clinically would have an optimal response remains a challenge. Future studies on a greater number of patients are needed to further develop a questionnaire to better identify clinical signs consistent with low back pain that will respond to spinal cord stimulation. Statements and DeclarationsO_ST_ABSSources of Financial SupportC_ST_ABSFinancial support for this project was provided by Nevro Conflict of InterestsDr. Ashwini Sharan reports personal fees from Neuspera, personal fees from Medtronic, grants and personal fees from Dixi, personal fees and other from Cerebral Therapeutics, outside the submitted work. Dr. Chengyuan Wu reports grants from Nevro, during the conduct of the study; personal fees from Nevro, personal fees from Abbott, personal fees from Medtronic, personal fees from Boston Scientific, personal fees from MicroSystems Engineering, outside the submitted work.

Complex Regional Pain Syndrome (CRPS) exhibits persistent disproportionate limb pain and hyperalgesia associated with neuroinflammatory and autonomic changes, typically after inciting limb injury. However, little is known about the progression of somatosensory changes over time. We reviewed cross-sectional studies employing standardised Quantitative Sensory Testing (QST) in accordance with the DFNS comprehensive somatosensory test protocol, stratified for CRPS duration. This study was registered with PROSPERO ID CRD42020216485. Reporting follows PRISMA guidelines. Databases searched were PubMed, Cochrane Library, Google Scholar, EMBASE, Web of Science and Scopus. Studies of adult patients with CRPS and QST according to the DFNS protocol were included. 1415 articles were screened and 23 studies meeting the inclusion criteria were included in quantitative analysis and narrative synthesis. Analysis was stratified by CRPS duration into an early ([&le;] 6 months), intermediate (6-12 months) and late (> 12 months) time window. Across all studies encompassing 2059 CRPS patients all somatosensory parameters deviated significantly from healthy subject profiles (all P < 0.001). All non-nociceptive detection parameters displayed a significant loss of sensitivity, while all nociceptive parameters as well as thermal and mechanical dysesthesias, i.e., paradoxical heat sensation and allodynia displayed a significant gain of sensitivity. Pressure pain threshold (PPT) showed the most drastic sensory gain with a large effect size (> 2 SD; Hedges g = 0.9) equivalent to more than half of CRPS patients exhibiting abnormal pressure hyperalgesia. Moreover, PPT significantly increased progressively with increasing CRPS duration (from 1.7 to 2.2 and 2.8 SD above normal). In late CRPS (> 12 months), additionally contralateral, mirror image test site sensory loss (P < 0.001) and pressure hyperalgesia (P < 0.001) became evident. Stratification for magnitude of pain did only modestly predict relevant differences in somatosensory profiles. Quantitative analysis of 23 cross-sectional QST studies in CRPS demonstrates pressure hyperalgesia as the signature CRPS sensory abnormality, distinguishing CRPS from neuropathic pain conditions. Further, pressure hyperalgesia exhibits a peculiar dramatic step progression between 4-12 months, without equivalent in other parameters. In late CRPS, somatosensory profiles become significantly abnormal at contralateral areas indicating loss of regionality. These findings have important implications for the classification of CRPS as a chronic primary pain condition, for understanding challenges to rehabilitative interventions, and for condition-subtyping.

Deficient descending pain inhibition assessed by conditioned pain modulation (CPM) is considered a common feature of various chronic pain disorders. Typically, CPM studies focus on one particular disorder making direct comparisons between disorders difficult. This cross-sectional study aimed to compare CPM effects between three clearly distinct chronic pain disorders and pain-free controls. Furthermore, patients were pooled with controls to explore whether subgroups showing different CPM effects could be separated independent of cohort membership. One hundred and forty participants (patients: 53 non-specific chronic low back pain [nsCLBP], 15 complex regional pain syndrome [CRPS], 14 neuropathic pain after spinal cord injury [painSCI]; 58 controls) were included. CPM effects were assessed in a remote, pain-free area using pressure pain thresholds as test stimulus and a cold water bath as conditioning stimulus. Cohort differences in CPM effects were analyzed using linear mixed models. The presence of subgroups showing different CPM effects was tested using latent class linear mixed models. CPM effects differed between cohorts (p = 0.011), driven mainly by reduced inhibitory CPM effects in patients with nsCLBP compared to patients with painSCI. Latent class analysis detected 3 subgroups with varying degrees of significant inhibitory CPM effects (ps [&le;] 0.002). All subgroups comprised patients and controls. These results oppose deficient descending pain inhibition as a common feature of chronic pain disorders. Additionally, the failure to identify subgroups without inhibitory CPM effects within a heterogenous patient/control sample challenges the utility of deficient CPM as predictor of chronic pain or treatment efficacy. PerspectiveInhibitory conditioned pain modulation, a measure of descending pain inhibition, is not consistently impaired across distinct chronic pain disorders. Furthermore, identifying individuals with impaired conditioned pain modulation within a heterogenous sample is difficult. Thus, for conditioned pain modulation to be clinically useful, its variability needs to be better understood.