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Patellofemoral pain (PFP) has poor long-term recovery outcomes. Central sensitization describes central nervous system changes altering pain modulation, which can complicate recovery (poorer prognosis and worse function). Signs of central sensitization include amplified pain facilitation, pain hypersensitivity, and impaired pain inhibition, which can be measured with temporal summation of pain (TSP), pressure pain thresholds (PPTs), and conditioned pain modulation (CPM), respectively. Sex differences exist for these test responses, but female-only PFP investigations of sensitization are uncommon. Understanding pain modulation in females with PFP could improve treatment protocols. To determine whether females with PFP exhibit signs of central sensitization (greater TSP, lower PPTs, and reduced CPM) compared with pain-free females. Cross-sectional study. Laboratory. Thirty-three females ([20 PFP, 13 pain free]; age: PFP 29.2 ± 7 years, pain free 28 ± 7 years; height: PFP 166.7 ± 5.9 cm, pain free 166 ± 9.5 cm; mass: PFP 66.7 ± 9.6 kg, pain free 69.3 ± 7.5 kg). Temporal summation of pain was assessed with 10 punctate stimuli applied to the knee and calculated by the difference in pain intensity between beginning and end responses. Pressure pain thresholds were tested at 4 sites (3 for local hypersensitivity [knee] and 1 for widespread hypersensitivity [hand]). Conditioned pain modulation was conducted by comparing PPTs during 2 conditions (baseline and ice immersion). Conditioned pain modulation response was defined as the percent difference between conditions. Between-groups differences in TSP response were analyzed with a Welch test. Separate Welch tests analyzed group comparisons of PPTs and CPM responses at 4 sites. Females with PFP exhibited greater TSP response (P =.019) and lower CPM response at patella center (P =.010) and hand sites (P =.007) than pain-free females. Pressure pain thresholds group differences were not observed at any site (P >.0125). Females with PFP modulate pain differently than pain-free females. Clinicians should recognize signs of central sensitization and their potential effect on treatment options. [ABSTRACT FROM AUTHOR]

Background: Achilles tendinopathy is a common overuse condition that can become persistent despite conservative treatment. Sensitization of both the peripheral and central nervous systems may contribute to the persistent pain. Both exercise and electrical stimulation have the potential to modulate the nervous system's sensitivity to painful stimuli. Hypothesis/Purpose: The purpose of this study was to describe the changes in pain sensitivity and self-reported function in runners with chronic Achilles tendon pain following sequential treatment with noxious electrical stimulation (NxES) and eccentric plantarflexion exercise. Study Design: Single group, repeated measures design. Methods: Sixteen participants with chronic Achilles tendinopathy completed the Lower Extremity Functional Scale (LEFS) and the Victorian Institute of Sport Assessment-Achilles scale (VISA-A) and quantitative sensory tests (pressure pain threshold, heat temporal summation, and heat pain threshold) at baseline, one week, seven weeks, and then at a one month post intervention follow-up. The NxES was applied for one week, then followed by plantarflexion eccentric exercise for six weeks. Changes across timepoints were assessed using repeated measures ANOVA and post hoc analysis to describe differences. Hedges g effect sizes were also calculated. Results: There was a significant improvement in LEFS (p < 0.001) and VISA-A (p < 0.001) from baseline to one month follow-up, with a mean change of 9.6 ± 7.7 and 19.4 ± 17.7 points respectively. Pressure pain threshold of the involved Achilles tendon increased over time (p < 0.001) with significant improvements after NxES application (p = 0.002) and after six weeks of eccentric exercise (p < 0.001). There were significant improvements from baseline to one month follow-up for heat temporal summation (p = 0.001) and heat pain threshold (p < 0.001). Conclusions: For individuals with chronic Achilles tendinopathy, a sequential treatment of NxES followed by eccentric exercise resulted in a clinically significant improvement in self-reported pain and function. During the first week of treatment there was a reduction in mechanical hyperalgesia during the NxES-only phase, while a large reduction in primary heat hyperalgesia and additional desensitization to mechanical pain occurred during the eccentric training phase of treatment. Level of Evidence: 2b [ABSTRACT FROM AUTHOR]

The home quantitative sensory testing tool-kit presented may help to provide tools for future research requiring cost-effective sensory testing that can be offered through telehealth. Quantitative sensory testing (QST) is a set of methods for quantifying somatosensory functioning. Limitations of laboratory-based QST (LQST) include high cost, complexity in training, lack of portability, and time requirements for testing. Translating QST to a home setting could facilitate future research and clinical care. The objective of this study was to develop a home QST (HQST) tool-kit that is cost-effective, easy to use, and detects changes in sensory and pain processing. Thirty-two young healthy adults underwent sensory testing on their nondominant forearm using standard in-person LQST, followed by "simulated HQST" using video guidance in a separate room from the investigator before and after application of either a lidocaine or capsaicin cream. We observed good agreement between HQST and LQST scores, with significant correlations observed between the pinprick, pressure, cold and heat measures (|ρ| range = 0.36-0.54). The participants rated the HQST protocol as highly acceptable and safe but can be improved in future implementations. Home QST was able to detect hypoesthesia to vibration after lidocaine cream application (P = 0.024, d = 0.502) and could detect hypoalgesia and hyperalgesia to pressure and heat pain sensitivity tests after application of lidocaine and capsaicin creams, respectively (P -value range = <0.001-0.036, d -value range = 0.563-0.901). Despite limitations, HQST tool-kits may become a cost-effective, convenient, and scalable approach for improving sensory profiling in clinical care and clinical research. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess subclinical peripheral diabetic neuropathy (PDN) in adolescents with type 1 diabetes mellitus (T1DM). Methods: Subjects included 53 T1DM patients (age (mean ± SE): 15.8 ± 0.54 years, disease duration: 6.0 ± 0.51 years and HbA1c: 7.9 ± 0.19%), and 37 healthy gender matched controls (age: 15.6 ± 0.52 years). PDN was assessed by vibration perception threshold (VPT) and by quantitative sensory testing (QST). In controls, 95% confidence intervals were calculated. Results: Among patients, VPT prevalence of abnormality ranged from 60–73.4% on different sites. Higher VPT was found in patients on all examined sites (p < 0.01). In controls, VPT correlated with height (r = 0.48, p = 0.05). Regarding QST prevalence of abnormality, cold detection threshold (CDT) ranged 7.3–39.0%, cold pain threshold (CPT) ranged 22.22–29.63%, hot detection threshold (HDT) ranged 34.14–63.41%, and hot pain threshold (HPT) ranged 15.79–36.84%. In patients, CPT correlated with BMI (r = 0.42, p = 0.05) and diabetes duration, (r = 0.40, p = 0.05), HPT correlated with age (r = 0.36, p = 0.05) and height (r = 0.35, p = 0.05), while in controls with BMI (r = 0.51, p = 0.05). No correlation of VPT or QST with HbA1c was observed. Conclusion: Adolescents with T1DM in this study, although asymptomatic, showed a high prevalence of impaired indices of PDN, highlighting potential clinical implications of early identification of PDN. [ABSTRACT FROM AUTHOR]

Background: Healthy individuals demonstrate considerable heterogeneity upon dynamic quantitative sensory testing assessment of endogenous pain modulatory mechanisms. For those who stratify into a 'pro-nociceptive profile' cohort, consisting of inefficient conditioned pain modulation (CPM) and elevated temporal summation of pain (TSP), the optimal approach for balancing the net output of pain modulatory processes towards anti-nociception remains unresolved. In this translational healthy human and rat study, we examined whether descending modulation countered spinal amplification during concurrent application of a CPM and TSP paradigm alongside pupillometry since pontine activity was previously linked to functionality of endogenous pain modulatory mechanisms and pupil dilation., Methods: Perceptual (quantitative sensory testing) and spinal neuronal (in vivo electrophysiology) assessment was performed in healthy humans and rats respectively upon application of parallel CPM/diffuse noxious inhibitory controls (cuff algometry) and TSP/wind-up (pinprick) paradigms alongside pupillometry., Results: In humans, repetitive pinprick stimulation produced TSP while concurrent application of a noxious conditioning stimulus did not affect pain ratings to a single pinprick stimulus, repetitive stimulation or the wind-up ratio. In rats, repetitive pinprick produced neuronal wind-up while concurrent application of a noxious conditioning stimulus inhibited neuronal responses to a single stimulus and repetitive stimulation but not the wind-up ratio. For pupillometry experiments, dilatory responses did not increase during application of a TSP or CPM paradigm in humans, while reliable rat responses were not obtained., Conclusions: Under the conditions of our study, spinal amplification mechanisms surpassed descending inhibitory controls while pupillometry did not offer a reliable indicator of endogenous pain modulatory mechanism function., Significance: In this translational healthy human and rat study, activity in descending inhibitory controls did not counter spinal amplification processes underpinned by wind up. Despite pupil dilation being previously linked to modulatory mechanisms, dilatory responses did not offer a reliable indicator of functionality. For pro-nociceptive individuals exhibiting inefficient conditioned pain modulation and/or high temporal summation of pain, dampening faciliatory mechanisms rather than augmenting top-down inhibitory processes may be a more effective pain-relief strategy., (© 2025 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Purpose of Review: Allodynia is characterized by a painful response to a non-noxious stimulus. This article reviews the pathophysiology, clinical presentation, differential diagnosis, diagnostic testing, and management approaches for the causes of allodynia., Recent Findings: Allodynia remains difficult to evaluate and manage. Despite ongoing research, significant progress is still needed to optimize the management of allodynia. Allodynia is a debilitating condition that can be difficult to treat. Diagnostic modalities and treatment options are limited. Advancements in diagnostic and treatment options are necessary to improve patient care., Competing Interests: Declarations. Ethics Approval and Consent to Participate: This article does not contain any studies with human or animal subjects performed by any of the authors. Papers of particular interest, published recently, have been highlighted as: * Of importance. **Of major importance. Competing Interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Fibromyalgia syndrome (FMS), a chronic pain syndrome affecting 0.2-6.6% of the general population, is known for its challenging diagnosis and treatment. The known dysregulation in the Endogenous Pain Modulatory System (EPMS) characteristic of the pathology contributes to enhanced pain sensitivity. Fibromyalgia patients, who are often overmedicated, may experience, in addition to the drug-related known adverse effects, effects on fibromyalgia sensory-related outcomes. Therefore, the focus of this analysis is to explore the bidirectional drug-sensory outcome interactions, indexed by the conditioned pain modulation (CPM), an important assessment element in regard to an EPMS's efficacy., Methods: Baseline data from a randomized, double-blind, single-center (Boston-based tertiary hospital) clinical trial (NCT03371225) were analyzed. Participants aged 18-65 with an FMS diagnosis and resistance to common analgesics were included. Demographic, clinical, and sensory variables, including CPM, temporal summation, and Pain-60 outcomes, were collected alongside a pain medication diary. Multivariable regression models adjusted for confounders were applied to explore associations between medication classes and quantitative sensory outcomes., Results: Out of 101 recruited FMS patients, we categorized the use of the following medications: antidepressants with 50% use ( n = 50), muscle relaxants with 26% use ( n = 26), and gabapentin with 25% use ( n = 25). The results showed that antidepressant use correlated with worsened CPM, Odds Ratio = 0.39 (95% CI = 0.17-0.91), while muscle relaxants were linked to increased TSPS, β coefficient = 0.72 (95% CI = 0.0021-1.4431). On the other hand, gabapentin use was associated with elevated Pain-60, OR = 2.68 (95% CI = 0.98-7.31). Interestingly, the use of low doses of opioids was not associated with altered sensory measures., Conclusion: This cross-sectional analysis suggests that common pain medications may affect quantitative sensory outcomes in FMS patients. We provided important insights into bidirectional drug-sensory outcome interactions and their influence on pain medicine.

Objective: As outlined in our previous study, this study aims to investigate the role of body mass index (BMI) as an effect modifier in the relationship between conditioned pain modulation (CPM) and clinical outcomes, including depression, quality of life, and pain in individuals with knee osteoarthritis (KOA)., Methods: This cross-sectional analysis is part of the DEFINE Study in Rehabilitation. A total of 113 participants with KOA, admitted to the Instituto de Medicina Física e Reabilitação (IMREA) rehabilitation program, were included. Clinical and neurophysiological assessments were conducted, focusing on CPM, the Hamilton Depression Rating Scale (HDRS), and the SF-36 health survey. BMI was stratified into two categories based on the mean BMI of 31.99 kg/m 2 , and linear regression models were used to evaluate BMI as an effect modifier in the relationship between CPM and clinical outcomes. p -values below 0.10 for interaction terms (CPM × BMI) indicated effect modification., Results: In participants with BMI < 31.99 kg/m 2 , increased CPM was significantly associated with improved depression scores (lower HDRS) and enhanced physical functioning, emotional well-being, and reduced limitations due to emotional problems (SF-36). In contrast, no significant associations between CPM and these outcomes were found in participants with BMI ≥ 31.99 kg/m 2 . The results suggest that a higher BMI disrupts the salutogenic effects of endogenous pain control, diminishing the beneficial associations between CPM and both physical and psychological outcomes, as previously observed in fibromyalgia patients., Conclusions: BMI acts as an effect modifier in the relationship between CPM and clinical outcomes in individuals with KOA. Obesity appears to hinder the beneficial relationships between clinical symptoms and CPM, leading to a less favorable link between physical and emotional functioning and CPM. These findings highlight the importance of considering BMI in treatment strategies for KOA, particularly when addressing the impact of lifestyle and other modifiable factors that influence pain modulation.

Introduction: Fibromyalgia has a high female predominance and research work has been focussing mainly on women., Objectives: We aimed to answer (1) gender differences in pain scores and quality of life, (2) any gender-specific subgroups defined by quantitative sensory testing (QST), and (3) correlations of QST parameters with pain intensity and questionnaire scores., Methods: We evaluated clinical presentations and QST profiles from 38 male and 38 age-matched female patients., Results: Women reported significantly higher scores in average daily pain, daily sleep interference score, average weekly pain, weekly sleep interference score, and revised fibromyalgia impact questionnaire (rFIQ). Based on LOGA classification, L0G2, mechanical allodynia or hyperalgesia without abnormal sensory loss, was the most common QST subtype which accounted for 28.9% of men and 26.3% of women. Approximately 34.2% of men and 26.3% of women displayed loss of function of small fibres with an increased cold or warm detection threshold. Cold detection threshold was negatively correlated with pain intensity and functional impairment, suggesting a peripheral mechanism. Central sensitization, defined as allodynia and hyperalgesia to thermal or mechanical stimuli, was found in two-thirds of male and female patients. Mechanical pain sensitivity was positively correlated with the severity of pain and associated symptoms in women, but not men., Conclusion: There was a marked gender difference in reported pain and quality of life. We have confirmed that central sensitization is a major mechanism for women. Our data suggested an important role of small fibre pathology in both men and women., Competing Interests: The authors have no conflict of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)