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This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.

Neuropathic pain, arising from lesions of the somatosensory nervous system, presents with diverse symptoms including ongoing pain, paroxysmal pain, and provoked pain, usually accompanied by sensory deficits. Understanding the pathophysiological mechanisms behind these symptoms is crucial for targeted treatment strategies. Neurophysiological techniques such as nerve conduction studies, reflexes, and evoked potentials help elucidate these mechanisms by assessing large myelinated non-nociceptive fibres and small nociceptive fibres. This argumentative review highlights the importance of tailored neurophysiological assessments for improving our understanding of the pathophysiological mechanisms behind neuropathic pain symptoms. [ABSTRACT FROM AUTHOR]

[Display omitted] • Abnormal activation of Group I mGluRs induces central sensitization. • Blocking Group Ⅰ mGluRs can alleviate neuropathic pain. • The existing Group I mGluRs orthosteric site antagonists have limitations. • Allosteric Modulators exhibit natural advantages due to allosteric modulation. • Structure based drug discovery may promote drug discovery targeting Group I mGluRs. Neuropathic pain (NP) is a widespread public health problem that existing therapeutic treatments cannot manage adequately; therefore, novel treatment strategies are urgently required. G-protein-coupled receptors are important for intracellular signal transduction, and widely participate in physiological and pathological processes, including pain perception. Group I metabotropic glutamate receptors (mGluRs), including mGluR1 and mGluR5, are predominantly implicated in central sensitization, which can lead to hyperalgesia and allodynia. Many orthosteric site antagonists targeting Group I mGluRs have been found to alleviate NP, but their poor efficacy, low selectivity, and numerous side effects limit their development in NP treatment. Here we reviewed the advantages of Group I mGluRs negative allosteric modulators (NAMs) over orthosteric site antagonists based on allosteric modulation mechanism, and the challenges and opportunities of Group I mGluRs NAMs in NP treatment. This article aims to elucidate the advantages and future development potential of Group I mGluRs NAMs in the treatment of NP. [ABSTRACT FROM AUTHOR]

Diseases of joints are among the most frequent causes of chronic pain. In the course of joint diseases, the peripheral and the central nociceptive system develop persistent hyperexcitability (peripheral and central sensitization). This review addresses the mechanisms of spinal sensitization evoked by arthritis. Electrophysiological recordings in anesthetized rats from spinal cord neurons with knee input in a model of acute arthritis showed that acute spinal sensitization is dependent on spinal glutamate receptors (AMPA, NMDA, and metabotropic glutamate receptors) and supported by spinal actions of neuropeptides such as neurokinins and CGRP, by prostaglandins, and by proinflammatory cytokines. In several chronic arthritis models (including immune‐mediated arthritis and osteoarthritis) spinal glia activation was observed to be coincident with behavioral mechanical hyperalgesia which was attenuated or prevented by intrathecal application of minocycline, fluorocitrate, and pentoxyfylline. Some studies identified specific pathways of micro‐ and astroglia activation such as the purinoceptor‐ (P2X7‐) cathepsin S/CX3CR1 pathway, the mobility group box‐1 protein (HMGB1), and toll‐like receptor 4 (TLR4) activation, spinal NFκB/p65 activation and others. The spinal cytokines TNF, interleukin‐6, interleukin‐1β, and others form a functional spinal network characterized by an interaction between neurons and glia cells which is required for spinal sensitization. Neutralization of spinal cytokines by intrathecal interventions attenuates mechanical hyperalgesia. This effect may in part result from local suppression of spinal sensitization and in part from efferent effects which attenuate the inflammatory process in the joint. In summary, arthritis evokes significant spinal hyperexcitability which is likely to contribute to the phenotype of arthritis pain in patients. [ABSTRACT FROM AUTHOR]

The appearance of contralateral effects after unilateral injury has been shown in various experimental pain models, as well as in clinics. They consist of a diversity of phenomena in contralateral peripheral nerves, sensory ganglia, or spinal cord: from structural changes and altered gene or protein expression to functional consequences such as the development of mirror-image pain (MP). Although MP is a well-documented phenomenon, the exact molecular mechanism underlying the induction and maintenance of mirror-like spread of pain is still an unresolved challenge. MP has generally been explained by central sensitization mechanisms leading to facilitation of pain impulse transfer through neural connections between the two sides of the central nervous system. On the contrary, the peripheral nervous system (PNS) was usually regarded unlikely to evoke such a symmetrical phenomenon. However, recent findings provided evidence that events in the PNS could play a significant role in MP induction. This manuscript provides an updated and comprehensive synthesis of the MP phenomenon and summarizes the available data on the mechanisms. A more detailed focus is placed on reported evidence for peripheral mechanisms behind the MP phenomenon, which were not reviewed up to now. [ABSTRACT FROM AUTHOR]

Central pain sensitivity (CS) is defined as an increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold inputs. The main aim of this paper is to investigate if and how specific psychological constructs are related with CS burden in patients with chronic headache (CH). Specifically, research question 1 explores the association of temperament, personality, childhood adversities, defense mechanisms and mental pain with CS burden. Research question 2 aims to test the role of the best predictors of CS burden in affecting the quality of life (QoL) using path analysis. A total of 508 women with CH completed a psycho-diagnostic survey. Results showed that higher levels of low sensory threshold (β = 0.200), bodily threat traumatic experiences (β = 0.156), neurotic defenses (β = 0.109) and mental pain (β = 0.343) emerged as the best predictors of higher CS burden. The model presented demonstrated a satisfactory fit (GFI = 0.984; NFI = 0.966; CFI = 0.979; RMSEA = 0.056 [95% CI 0.028–0.085]) with large and medium effect sizes on physical (−0.654) and psychological QoL (−0.246). The study showed a key role of psychological dimensions in CS burden levels and their relationships with QoL in CH patients. From a clinical perspective, these results suggest the importance of evaluating the level of CS burden during the clinical assessment for chronic pain conditions such as CH, since it may contribute to guide patients to tailored psychological and medical treatments, thereby saving time and costs on diagnostic procedures for chronic pain. [ABSTRACT FROM AUTHOR]

Aim: Evaluate the efficacy and safety ® (olokizumab) in patients with rheumatoid arthritis (RA) in real‐world clinical practice, with a targeted assessment of patient report outcomes (PRO) and central sensitization. Methods: An open‐label observational non‐interventional study was conducted, enrolling 183 patients with moderate and severe RA activity. All patients received OKZ 64 mg SC as injections every 4 weeks (Q4W) with methotrexate. The patients' follow‐up period was 24 weeks or less. RA activity (DAS28‐CRP), pain severity (NRS), patient global assessment (PGA, NRS), functional impairment (NRS), fatigue (FACIT‐F), central sensitization (central sensitization inventory, CSI), and symptoms of neuropathic pain (PainDETECT) were evaluated. Results: The study cohort was comprised of 144 patients. And 39 patients were lost to follow‐up, refused OKZ treatment, or were not dosed with OKZ for administrative reasons. In 6 months, DAS28‐CRP decreased to 3.3 ± 0.9 (p <.001) and statistically significant reductions in pain intensity, PGA, functional impairment, and fatigue were achieved. Pain intensity decreased as early as 2 days after the first OKZ administration (p <.05). The number of patients with CSI >40 in 24 weeks decreased from 71.0% to 21.0% (p <.001), with PainDETECT >18 – from 21.5% to 13.2%. NSAIDs use decreased from 70.8% to 33.8% (р <.001), steroids – from 54.2% to 32.6%. AEs were reported in 14.2% patients, serious events were observed in three patients. Conclusion: OKZ is effective in reducing RA activity and controlling chronic pain related to dysfunction of the nociceptive system. [ABSTRACT FROM AUTHOR]

Breast cancer represents the most common type of malignant neoplasm worldwide. Advances in diagnosis and treatment have increased the life expectancy of patients. However, the sequelae associated with the treatment of the disease such as chronic pain, kinesiophobia and loss of physical function in breast cancer survivors (BCS) are a long-term health problem. Therapeutic strategies are required for the treatment of chronic sequelae in this population. To evaluate the effectiveness of a pain neuroscience education (PNE) and therapeutic exercise (TE) for the treatment of chronic sequelae in BCS. Quasi-experimental repeated measures study. The intervention lasted 9 weeks, with 3 educational and 24 exercise sessions. Pain frequency and intensity (VAS scale), neuropathic pain (DN4), kinesiophobia level (TSK-11V), central sensitization (CSI-Sp), functionality of the affected arm (ULFI-Sp) and active joint range (ROM) with goniometry were measured at baseline, 3rd, 6th and 9th week. Statistical analysis included Friedman's test and ANOVA according to normality criteria. A total sample of 26 BCS participate in the study. Significant statistical changes were found from the 3rd week of treatment in the frequency and intensity of pain, kinesiophobia and neuropathic pain (p < 0.05). All variables had significant changes at the 9th week (p = 0.001). The results of the present investigation suggest that the combination of PNE and TE are effective in treating sequelae at short term in BCS with chronic pain. [ABSTRACT FROM AUTHOR]

Background/Objectives: Fibromyalgia (FM) is a syndrome characterized by widespread chronic pain as the primary symptom. Neurophysiological pain mechanisms, such as the function of the descending inhibitory system, are impaired in this condition. The main objective of this study was to compare the results of two paradigms to evaluate CPM in women with FM. The secondary objective was to correlate the results of each CPM paradigm with the clinical status of patients with FM. Methods: One hundred and three FM women were divided into two groups: fifty patients diagnosed with FM were assigned to the conditioned pain modulation (CPM) group using a cold pressor stimulus, and fifty-three patients were assigned to the CPM group using the ischemic pressure stimulus. The main outcome measures were pain intensity, disability, mechanical hyperalgesia, and CPM. Results: The primary analysis revealed significant differences between the results obtained from the different CPM protocols. Poorer outcomes in the cold pressor test correlated with higher pain intensity and a greater disability index. Conclusions: Pain modulation abnormalities in FM patients were evident when using either the cold pressor or ischemic pressure stimuli to establish the CPM paradigm. The cold pressor conditioning stimulus elicited a stronger response than the ischemic pressure stimulus in FM patients. [ABSTRACT FROM AUTHOR]

Purpose: Exacerbations of osteoarthritis (OA) pain significantly impair activities of daily living and walking, thereby reducing quality of life. Despite various treatments, persistent pain remains a challenge, particularly in patients with hip OA, where pain perception mechanisms extend beyond nociceptive pain. This study examined the pain characteristics in patients with hip OA, with an emphasis on neuropathic pain and central sensitization (CS). Methods: A total of 421 patients scheduled for unilateral total hip arthroplasty were analyzed using the painDETECT score and Central Sensitization Inventory to classify the pain types as nociceptive (Noc), CS, neuropathic (Neu), or neuropathic with CS (NeuCS). Results: The results indicated that 72.9% of patients experienced Noc pain, while 5.0% experienced combined NeuCS pain. The Neu and NeuCS groups exhibited significantly lower modified Harris Hip Score and EuroQol-5 Dimensions Questionnaire (EQ-5D) scores than the Noc group, indicating worse clinical outcomes and quality of life. Neu pain was more intense at rest, and when combined with CS it significantly diminished the quality of life. Conclusion: These findings highlight the need for mechanism-based pain treatment strategies, such as Neu pain and CS components, which independently and cumulatively affect clinical scores and quality of life. This study highlights the importance of early recognition and targeted treatment of these pain mechanisms in patients with hip OA. Future research should focus on evaluating therapeutic interventions for Neu pain and CS to optimize patient outcomes.

Abstract Neuropathic pain, arising from lesions of the somatosensory nervous system, presents with diverse symptoms including ongoing pain, paroxysmal pain, and provoked pain, usually accompanied by sensory deficits. Understanding the pathophysiological mechanisms behind these symptoms is crucial for targeted treatment strategies. Neurophysiological techniques such as nerve conduction studies, reflexes, and evoked potentials help elucidate these mechanisms by assessing large myelinated non-nociceptive fibres and small nociceptive fibres. This argumentative review highlights the importance of tailored neurophysiological assessments for improving our understanding of the pathophysiological mechanisms behind neuropathic pain symptoms.

Abstract Galcanezumab, a monoclonal antibody targeting the calcitonin gene-related peptide pathway (CGRP mAb), acts peripherally due to its large size. However, recent studies have suggested that CGRP mAbs may also have a central mode of action. This study aimed to evaluate the central effects of galcanezumab on migraine central sensitization.This prospective real-world study was conducted at three headache centers in Japan between May 2021 and May 2022. Patients treated with galcanezumab for migraines were included in the study. The primary outcome was the change in the validated Central Sensitization Inventory (CSI) score from baseline to six months of treatment. We also assessed changes in the Allodynia Symptom Checklist (ASC-12) score. Eighty-six patients with migraine (73 female and 13 male) were analyzed. At 6 months, CSI and ASC-12 scores were significantly reduced compared to baseline (CSI: 36.0 vs. 29.3, p

Background: The insula and dorsal anterior cingulate cortex (dACC) are core brain regions involved in pain processing and central sensitization, a shared mechanism across various chronic pain conditions. Methods to modulate these regions may serve to reduce central sensitization, though it is unclear which target may be most efficacious for different measures of central sensitization.Objective/Hypothesis: Investigate the effect of low-intensity focused ultrasound (LIFU) to the anterior insula (AI), posterior insula (PI), or dACC on conditioned pain modulation (CPM) and temporal summation of pain (TSP). Methods: N = 16 volunteers underwent TSP and CPM pain tasks pre/post a 10 min LIFU intervention to either the AI, PI, dACC or Sham stimulation. Pain ratings were collected pre/post LIFU. Results: Only LIFU to the PI significantly attenuated pain ratings during the TSP protocol. No effects were found for the CPM task for any of the LIFU targets. LIFU pressure modulated group means but did not affect overall group differences. Conclusions: LIFU to the PI reduced temporal summation of pain. This may, in part, be due to dosing (pressure) of LIFU. Inhibition of the PI with LIFU may be a future potential therapy in chronic pain populations demonstrating central sensitization. The minimal effective dose of LIFU for efficacious neuromodulation will help to translate LIFU for therapeutic options.

Abstract Posttraumatic headache (PTH) is common following traumatic brain injury and impacts quality of life. We investigated descending pain modulation as one possible mechanism for PTH and correlated it to clinical measures. Pain-related evoked potentials (PREP) were recorded in 26 PTH-patients and 20 controls after electrical stimulation at the right hand and forehead with concentric surface electrodes. Conditioned pain modulation (CPM) was assessed using painful cutaneous electric stimulation (PCES) on the right hand as test stimulus and immersion of the left hand into 10 °C-cold water bath as conditioning stimulus based on changes in pain intensity and in amplitudes of PCES-evoked potentials. All participants completed questionnaires assessing depression, anxiety, and pain catastrophising. PTH-patients reported significantly higher pain ratings during PREP-recording in both areas despite similar stimulus intensity at pain threshold. N1P1-amplitudes during PREP and CPM-assessment were lower in patients in both areas, but statistically significant only on the hand. Both, PREP-N1-latencies and CPM-effects (based on the N1P1-amplitudes and pain ratings) were similar in both groups. Patients showed significantly higher ratings for anxiety and depression, which did not correlate with the CPM-effect. Our results indicate generalized hyperalgesia for electrical stimuli in both hand and face in PTH. The lacking correlation between pain ratings and EEG parameters indicates different mechanisms of pain perception and nociception.

The study aims to investigate the relationship between serum hornerin levels and disease severity and pain scores and to evaluate hornerin’s potential as a biomarker and its role in understanding the etiopathogenesis of fibromyalgia (FM).The study included 36 female patients diagnosed with FM and 36 healthy female volunteers, matched for age and body mass index (BMI). Disease functional status and pain intensity in FM were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and Visual Analog Scale (VAS), respectively. Serum hornerin levels were measured using a commercial ELISA kit.The mean age and BMI were 47.08 ± 9.76 and 27.17 ± 4.19 in the patient group and 43.61 ± 12.40 and 25.43 ± 5.25 in the control group. Serum hornerin levels averaged 2.64 ± 0.50 ng/mL in the patient group and 2.33 ± 0.49 ng/mL in the control group, showing significantly higher levels in the FM group (p=0.009). The median VAS score for FM patients was 8.0 (6.25–10) cm, and the mean FIQ score was 61.64 ± 15.09. The cutoff value for hornerin was determined to be 2.44 ng/mL (with 63.9 % sensitivity and 61.1 % specificity). A positive correlation was found between serum hornerin levels and BMI values.Elevated hornerin levels were observed in FM cases. Hornerin has the potential to be explored as a biomarker for diagnosing FM. [ABSTRACT FROM AUTHOR]

Galcanezumab, a monoclonal antibody targeting the calcitonin gene-related peptide pathway (CGRP mAb), acts peripherally due to its large size. However, recent studies have suggested that CGRP mAbs may also have a central mode of action. This study aimed to evaluate the central effects of galcanezumab on migraine central sensitization.This prospective real-world study was conducted at three headache centers in Japan between May 2021 and May 2022. Patients treated with galcanezumab for migraines were included in the study. The primary outcome was the change in the validated Central Sensitization Inventory (CSI) score from baseline to six months of treatment. We also assessed changes in the Allodynia Symptom Checklist (ASC-12) score. Eighty-six patients with migraine (73 female and 13 male) were analyzed. At 6 months, CSI and ASC-12 scores were significantly reduced compared to baseline (CSI: 36.0 vs. 29.3, p < 0.001; and ASC-12: 5.55 vs. 4.26, p < 0.01). Furthermore, these effects were observed as early as three months of treatment. In this study, we demonstrated the real-world efficacy of galcanezumab in improving central sensitization in migraine, with significant effects seen in the early phase of treatment.Please check and confirm whether the corresponding author mail ID is correctly processed We checked it. And, please kindly re-check !!!! !!! To use this Article for commercial purposes should be okay.!!! We asked you to publish this article with the following license; Creative Commons licence CC BY: This licence allows readers to copy, distribute and transmit the Article as long as it is attributed back to the author. Readers are permitted to alter, transform or build upon the Article, and to use the Article for commercial purposes.Please confirm the inserted city name is correct in affiliation 3 and amend if necessary.Checked.Per style, a structured abstract is not allowed so we have changed the structured abstract to an unstructured abstract. Please check and confirm.We Checked. And again, please kindly make sure the followings; !!! Please kindly re-check !!! To use this Article for commercial purposes should be okay.!!! We asked you to publish this article with the following license; Creative Commons licence CC BY: This licence allows readers to copy, distribute and transmit the Article as long as it is attributed back to the author. Readers are permitted to alter, transform or build upon the Article, and to use the Article for commercial purposes. Trial registration: This study was registered with UMIN-CTR on May 2, 2021 (UMIN000044096). [ABSTRACT FROM AUTHOR]

Introduction: Previously, we had observed that immediate pain reduction after one acupuncture treatment was associated with high temporal summation of pain (TS) at a pain free control site and younger age in a mixed population of chronic pain patients. The aim of the present study was to verify these results in chronic non-specific low back pain (LBP) and to collect pilot data on the association between TS and the response to an acupuncture series. Methods: TS at a pain free control site (back of dominant hand) and at the pain site was quantified by the pin-prick induced wind-up ratio (WUR) in 60 LBP patients aged 50 years or younger. Response to one acupuncture treatment was assessed by change in pain intensity and pressure pain threshold (PPT) at the pain site. The primary hypothesis was that a high TS (WUR > 2.5) would be associated with a clinically relevant reduction in pain intensity of at least 30%. In study part two, 26 patients received nine additional treatments. Response to the acupuncture series was assessed by the pain intensity during the last week, the PPT and the Hannover functional ability questionnaire (FFbH-R). Results: An immediate reduction in pain intensity of at least 30% was frequent irrespective of TS at the control site (low vs. high TS 58% vs. 72%, p = 0.266). High TS at the pain site was also not significantly associated with a clinically relevant immediate reduction in pain intensity (low vs. high TS 46% vs. 73%, p = 0.064). The PPT was not changed after one acupuncture treatment. Study part two did not reveal a consistent association between TS at the control site and any of the outcome measures but also a trend toward a higher chance for a clinically relevant response along with low TS at the pain site. Conclusion: Our results do not suggest an important role of TS for predicting a clinically important acupuncture effect or the response to a series of 10 acupuncture treatments in patients with chronic non-specific LBP. Overall high response rates imply that acupuncture is a suitable treatment option for LBP patients irrespective of their TS. [ABSTRACT FROM AUTHOR]

According to the neurocognitive model of attention to pain, when the attentional resources invested in a task unrelated to pain are high, limited cognitive resources can be directed toward the pain. This is supported by experimental studies showing that diverting people's attention away from acute pain leads to experiencing less pain. Theoretical work has suggested that this phenomenon may present a top-down modulatory mechanism for persistent pain as well. However, conclusive empirical evidence is lacking. To fill this gap, we used a preregistered, double-blind, between-subject study design to investigate whether performing a tailored, demanding, and engaging working memory task unrelated to pain (difficult) vs a task that requires less mental effort to be performed (easy), could lead to lower development of secondary hypersensitivity--a hallmark of central sensitization. Eighty-five healthy volunteers, randomly assigned to one of the 2 conditions, performed a visual task with a different cognitive load (difficult vs easy), while secondary hypersensitivity was induced on their nondominant forearm using high-frequency stimulation. To assess the development of secondary hypersensitivity, sensitivity to mechanical stimuli was measured 3 times: T0, for baseline and 20 (T1) and 40 (T2) minutes after the procedure. We did not observe any significant difference in the development of secondary hypersensitivity between the 2 groups, neither in terms of the intensity of mechanical sensitivity nor its spatial extent. Our results suggest that a top-down modulation through attention might not be sufficient to affect pain sensitization and the development of secondary hypersensitivity. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a common pain syndrome, which seriously affects the quality of life of patients. The mechanism of neuropathic pain is complex. Peripheral tissue injury can trigger peripheral sensitization; however, what really plays a key role is the sensitization of the central nervous system. Central sensitization is a key factor in the perception of chronic pain. Central sensitization refers to the increased sensitivity of the central nervous system to pain treatment, which is related to the change of the functional connection mode of the neural network. The current study aims to reveal the basic molecular mechanisms of central sensitization, including the involvement of P2 purine X4 receptor and brain-derived neurotrophic factor. In terms of treatment, although there are drugs and physical therapy, the accuracy of targeting is limited and the efficacy needs to be further improved. Future therapeutic strategies may involve the development of new drugs designed to specifically inhibit the central sensitization process. This article focuses on the effector molecules involved in central sensitization, aiming to elucidate the pathogenesis of neuropathic pain and provide a basis for the development of more effective treatment models. [ABSTRACT FROM AUTHOR]

Introduction: Nociplastic pain (NP), classified as a third type of pain alongside nociceptive and neuropathic pain, is chronic pain arising from the amplification of nociceptive stimuli through central sensitization, despite the absence of tissue damage, sensory nerve damage, or disease. An important clinical feature of NP is that it is not only associated with pain but also with sensory hypersensitivity to sound and light and cognitive dysfunction, including mood and attention disorders. Recent studies have suggested that depression and developmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), coexist with NP at high frequency. Additionally, cognitive impairment in individuals with NP may be associated with these psychiatric comorbidities. However, to our knowledge, there are no reports on (1) multidimensional evaluation and diagnostic details of abdominal NP in adults with ADHD/ASD; (2) how ADHD drugs and antidepressants are administered when ADHD and depression coexist with NP; and (3) how central sensitization, brain function, and family relationship problems underlying NP are altered by treatments of ADHD and depression. Case presentation: Herein, we present the case of a 51-year-old woman with abdominal NP. She developed severe right lower abdominal pain and underwent a thorough medical examination; however, the physical, medical cause remained unknown, making treatment challenging. Additionally, she took time off work as she began to complain of insomnia and anxiety. She was referred to our pain center, where a diagnosis of depression, ADHD, and ASD was confirmed, and treatment with ADHD medication was initiated. While ADHD medications alone did not yield sufficient improvement, a combination of methylphenidate and the antidepressant venlafaxine eventually led to improvements in abdominal NP, depression, ADHD symptoms, central sensitization, and family relationship issues. During treatment, cerebral blood flow in the anterior cingulate, prefrontal, and parietal cortices also improved. Conclusion: The treatment of comorbid depression is important while treating NP, and venlafaxine may be effective, especially in cases of comorbid ADHD/ASD. Screening for developmental disorders and depression is required in patients with abdominal NP. [ABSTRACT FROM AUTHOR]

Background. Chronic pain has been investigated in pathophysiology and different mechanisms underlying this condition has been described. Despite the plentiful literature regarding this topic and the different pharmacological treatments proposed, patients often referred inadequate relief from medication. The aim of this narrative review was to investigate the different rehabilitative approach in the management of chronic pain and their efficacy. Methods. A systematic narrative review has been conducted considering randomize controlled trials and systematic reviews published within the past 5 years. Results. 13 papers on chronic pain and 6 papers on nociplastic pain has been described in the main aspects analyzed. Conclusions. No one treatment appears to be more effective than another but often it is the combination of several treatments that gives the best results. More studies, evaluating in particular specific exercises with clear proprioceptive elements, should be conducted to best analyzed their role in the management of chronic pain. Clin Ter 2024; 175 (5):337-345 doi: 10.7417/CT.2024.5139 [ABSTRACT FROM AUTHOR]

Central sensitization and neuropathic pain may develop in rheumatological diseases. This study aimed to investigate the presence of central sensitization and neuropathic pain in patients with rheumatoid arthritis (RA). We used the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire to evaluate neuropathic pain (NP) in patients with RA. The presence of central sensitization in patients was evaluated using the central sensitization inventory (CSI). Demographic and clinical data were obtained from patients and interviews. Beck Depression Scale (BDS) was used to evaluate the mood of the patients, and the Short Form-36 (SF-36) quality of life scale was used to evaluate the quality of life. A total of 104 patients participated in our study, and 33 (31.7%) of them were found to be NP. CSI scores indicated central sensitization in 41 (39.4%) of the patients. A positive significant relationship was detected between LANSS and Visual Analog Scale (VAS), BDI, and Disease Activity Score 28 (DAS28). Central sensitization (CS) and neuropathic pain (NP) significantly contribute to functional disability in RA patients. Central sensitization and neuropathic pain significantly contribute to functional disability in patients experiencing neuropathic pain, with CS having a detrimental impact on their quality of life. Thus, it is imperative to consider neuropathic pain and CS during disease monitoring and follow-up. [ABSTRACT FROM AUTHOR]

Background/Objectives: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by peripheral arthritis, enthesitis, spondylitis and psoriasis. The objective of this study was to examine the prevalence of central sensitization (CS) and its impact on the clinical and functional aspects of PsA. Methods: Adult patients with PsA according to the Classification of Psoriatic Arthritis (CASPAR) criteria were included in this cross-sectional observational study. The Central Sensitization Inventory (CSI) was used to assess the presence of CS. The study evaluated the impact of CS on individuals by analyzing many factors including demographic information, laboratory findings, clinical features, disease activity, quality of life, severity of sleeplessness, frequency of depression and anxiety. The patients were categorized into distinct groups based on the existence and intensity of CS, and a comparative analysis was conducted on their respective outcomes. Results: A total of 103 PsA patients with a mean age of 43.2 (SD: 6.7) years and including 42 (40.8%) males were included. The mean CSI score was 45.4 (SD: 15.1), and 67 (65.1%) patients had CS. The logistic regression analysis revealed that the variables Psoriasis Area Severity Index (PASI), General Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI) exhibit considerable predictive power in relation to the outcome variable CS (p < 0.05). PASI was observed as the most important variable in predicting CS (OR 9.70 95% CI: 1.52–62.21). Conclusions: CS has demonstrable efficacy in influencing laboratory, clinical, and functional markers among individuals with PsA. When assessing pain sensitivity in these patients, it is important to take into account the presence of CS. [ABSTRACT FROM AUTHOR]

Objectives Central pain mechanisms may be prominent in a considerable subset of rheumatology patients with persistent pain. Several self-report instruments have been used in previous research to infer the presence and severity of central sensitization (CS) that stem from different definitions or approaches of CS. The current study aimed to evaluate and quantify the overlap of actual symptoms measured among self-report measures of CS in rheumatology. Methods We used Fried's (2017) comprehensive systematic approach to analyse the content of five commonly used or typical self-report measures (Generalized Pain Questionnaire, Pain Sensitivity Questionnaire, Central Sensitization Inventory, Central Aspects of Pain in the Knee scale and the painDETECT) used in rheumatology research and to visualize and quantify the overlap in symptoms measured. Results The five instruments together measured 39 different symptoms, most of which could be grouped into nociplastic pain manifestations (7 symptoms), neuropathic pain qualities (5 symptoms), and psychosomatic symptoms and emotional distress (25 symptoms). Most symptoms (74.4%) were unique to a single instrument. Thermal allodynia was the most frequently measured symptom across the different instruments, assessed in four of the measures. Average content overlap was very low and ranged from no overlap at all to moderate overlap (Jaccard index = 0.43) between pairs of instruments. Conclusion There is high heterogeneity and limited overlap in the content of self-report measures used to infer central pain sensitization. This may lead to results that are specific to the particular instrument and may limit the generalizability and comparability of study findings in rheumatology research. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia (FM) is a complex multidimensional disorder primarily characterized by chronic widespread pain, significantly affecting patients' quality of life. FM is associated with some clinical signs found with quantitative sensory testing (QST), sleep disturbance, or psychological problems. This study aims to explore the associations between pressure pain thresholds (PPTs), conditioned pain modulation (CPM), clinical status, and sleep quality in FM patients, offering insights for better clinical management and assessment tools. Methods: This secondary analysis utilized data from a clinical trial involving 129 FM patients. Various assessments, including the Fibromyalgia Impact Questionnaire (FIQ), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), and Jenkins Sleep Scale (JSS), were employed to evaluate the clinical and psychological status and sleep quality. PPTs and CPM were measured to understand their relationship with clinical parameters. Results: Our findings revealed that PPTs and CPM are not significantly associated with the clinical status or sleep quality of FM patients. Instead, pain catastrophizing and anxiety state showed a stronger correlation with the impact of fibromyalgia and sleep disturbances. These results highlight the importance of psychological and cognitive factors in managing FM. Conclusions: The study suggests that while PPTs and CPM may not be reliable biomarkers for clinical status in FM, the use of comprehensive assessments including FIQ, PCS, STAI, and JSS can provide a more accurate evaluation of patients' condition. These tools are cost-effective, can be self-administered, and facilitate a holistic approach to FM management, emphasizing the need for personalized treatment plans. [ABSTRACT FROM AUTHOR]

Human assumed central sensitization (HACS) is a potential pathophysiological mechanism underlying a group of musculoskeletal disorders. HACS may negatively influence the outcomes of surgical or interventional procedures. The present study aimed to investigate the impact of HACS on treatment outcomes of transforaminal epidural steroid injection (TFESI). Patients who received fluoroscopy-guided single-level lumbosacral TFESI between January 2020 and January 2021 were included in the study. The patients were divided into two groups with respect to the existence of HACS. Patients were assessed before the procedure, at the third week, and at the third month after the procedure. The presence of HACS was investigated by central sensitization inventory (CSI). The Numerical Rating Scale (NRS), Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI) were used for patient assessment. A total of 65 patients were included in the study. Thirty-one of the patients had HACS. There was no difference between the groups in terms of demographic data. Significant improvement in NRS was found at 3rd week and 3rd month compared to the baseline. BDI and ODI scores were also significantly reduced at the end of 3 months (p< 0.001). NRS scores at all time points were significantly lower in patients without HACS (p< 0.05). The presence of HACS has a negative effect on pain scores, disability, and mental state in patients undergoing TFESI. [ABSTRACT FROM AUTHOR]

Recently, we showed that while atogepant—a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist—does not fully prevent activation of meningeal nociceptors, it significantly reduces a cortical spreading depression (CSD)-induced early response probability in C fibres and late response probability in Aδ fibres. The current study investigates atogepant effect on CSD-induced activation and sensitization of high threshold (HT) and wide dynamic range (WDR) central dura-sensitive trigeminovascular neurons. In anaesthetized male rats, single-unit recordings were used to assess effects of atogepant (5 mg/kg) versus vehicle on CSD-induced activation and sensitization of HT and WDR trigeminovascular neurons. Single cell analysis of atogepant pretreatment effects on CSD-induced activation and sensitization of central trigeminovascular neurons in the spinal trigeminal nucleus revealed the ability of this small molecule CGRP receptor antagonist to prevent activation and sensitization of nearly all HT neurons (8/10 versus 1/10 activated neurons in the control versus treated groups, P = 0.005). In contrast, atogepant pretreatment effects on CSD-induced activation and sensitization of WDR neurons revealed an overall inability to prevent their activation (7/10 versus 5/10 activated neurons in the control versus treated groups, P = 0.64). Unexpectedly however, in spite of atogepant's inability to prevent activation of WDR neurons, it prevented their sensitization (as reflected their responses to mechanical stimulation of the facial receptive field before and after the CSD). Atogepant' ability to prevent activation and sensitization of HT neurons is attributed to its preferential inhibitory effects on thinly myelinated Aδ fibres. Atogepant's inability to prevent activation of WDR neurons is attributed to its lesser inhibitory effects on the unmyelinated C fibres. Molecular and physiological processes that govern neuronal activation versus sensitization can explain how reduction in CGRP-mediated slow but not glutamate-mediated fast synaptic transmission between central branches of meningeal nociceptors and nociceptive neurons in the spinal trigeminal nucleus can prevent their sensitization but not activation. [ABSTRACT FROM AUTHOR]

Chronic pain is a prevalent condition with a multifaceted pathogenesis, where epigenetic modifications, particularly DNA methylation, might play an important role. This review delves into the intricate mechanisms by which DNA methylation and demethylation regulate genes associated with nociception and pain perception in nociceptive pathways. We explore the dynamic nature of these epigenetic processes, mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes, which modulate the expression of pro- and anti-nociceptive genes. Aberrant DNA methylation profiles have been observed in patients with various chronic pain syndromes, correlating with hypersensitivity to painful stimuli, neuronal hyperexcitability, and inflammatory responses. Genome-wide analyses shed light on differentially methylated regions and genes that could serve as potential biomarkers for chronic pain in the epigenetic landscape. The transition from acute to chronic pain is marked by rapid DNA methylation reprogramming, suggesting its potential role in pain chronicity. This review highlights the importance of understanding the temporal dynamics of DNA methylation during this transition to develop targeted therapeutic interventions. Reversing pathological DNA methylation patterns through epigenetic therapies emerges as a promising strategy for pain management. [ABSTRACT FROM AUTHOR]

Endometriosis, often associated with chronic pelvic pain, can lead to anxiety and depression. This study investigates the role and mechanism of Glycine receptor alpha 3 (Glrα3) in the central sensitization of pain in endometriosis, aiming to identify new therapeutic targets. Using a Glrα3 knockout mouse model of endometriosis, we employed behavioral tests, qPCR, immunofluorescence, Nissl staining, MRI, and Western blot to assess the involvement of Glrα3 in central pain sensitization. Our results indicate that endometriosis-induced hyperalgesia and anxiety–depressive-like behaviors are linked to increased Glrα3 expression. Chronic pain in endometriosis leads to gray matter changes in the sensory and insular cortices, with Glrα3 playing a significant role. The inhibition of Glrα3 alleviates pain, reduces neuronal abnormalities, and decreases glial cell activation. The absence of Glrα3 effectively regulates the central sensitization of pain in endometriosis by inhibiting glial cell activation and maintaining neuronal stability. This study offers new therapeutic avenues for the clinical treatment of endometriosis-related pain. [ABSTRACT FROM AUTHOR]

Introduction: Chronic neck pain (CNP) is a global public health problem, with high prevalence and absenteeism rates. Central sensitization (CS) as a basis for chronic pain may play an essential role in its development and progression. It is often comorbid with low conditioned pain modulation (CPM) effects, cognitions, and psychological problems. Objectives: The purposes of this study were to (1) explore the relationship between pain-related cognitions and psychological factors, CPM effects, and the central sensitization inventory (CSI) scores; and (2) determine whether cognitions and psychological factors can predict CSI scores and CPM effects in individuals with CNP. Methods: Fifty-four individuals with CNP were recruited for this cross-sectional study. The following outcome measures were evaluated: The CSI (screening tool) was compared with the cold pressor test (CPT), which was the psychophysical test used to assess the CPM; neck pain intensity using the visual analogue scale (VAS), as well as pain-related cognitions (including kinesiophobia and pain catastrophization) and psychological states (including anxiety and depression) using self-report questionnaires. Results: CSI score was not associated with the CPM effect (r = 0.257, p > 0.05), and no cognitions or psychological factors were associated with CPM (p > 0.05), but CSI score was moderately positively correlated with kinesiophobia (r = 0.554, p < 0.01), lowly positively correlated with pain catastrophization (r = 0.332, p = 0.017) and anxiety (r = 0.492, p < 0.01), but not depression (r = 0.207, p = 0.132). Multiple linear regression analysis showed that kinesiophobia (B = 1.308, p < 0.01) and anxiety (B = 1.806, p = 0.02) were significant positive predictors of CSI score. Conclusions: The findings confirm some of our hypotheses. Accordingly, the findings inferred that the CSI does not seem to respond to CPM effect in patients with CNP effectively. In addition, CSI score was associated with cognitions and psychological factors, of which kinesiophobia and anxiety were effective predictors. In clinical practice, pain-related cognitions and psychological factors should be fully considered to manage neck pain efficiently. [ABSTRACT FROM AUTHOR]

Pain control and patient satisfaction after total knee arthroplasty (TKA) have room for improvement. While studies have reported better analgesic outcomes with antidepressants like duloxetine in patients who do not have central sensitivity (CS), we undertook this trial to determine the short and midterm analgesic role of low-dose duloxetine in patients who do not have CS. This prospective, double-blinded, randomized, placebo-controlled trial was conducted in 106 patients undergoing single-setting, bilateral TKA under spinal anesthesia. There were 2 matched groups, with one given 20 mg of duloxetine and the other given a placebo (similar in appearance and weight) from preoperative day 2 to postoperative day 28. Follow-ups were scheduled at 48-hours, 1-week, 2-weeks, 4-weeks, and 3-months. Pain was measured using a visual analogue scale at rest and visual analogue scale at mobilization (mVAS). Secondary measures included additional non-steroidal anti-inflammatory drug consumption, patient satisfaction, and safety profile. The visual analogue scale at rest in the duloxetine group was better in the first 48 hours (6.38 ± 1.32 versus 7.02 ± 0.99; P =.017), 1-week (4.76 ± 1.24 versus 5.89 ± 1.06; P <.001), and 2-weeks (3.34 ± 1.19 versus 4.26 ± 1.02; P <.001) follow-up. The mVAS remained significantly higher in the duloxetine group in the first 48 hours (7.23 ± 1.12 versus 8.21 ± 0.69; P <.001), 1-week (5.83 ± 1.11 versus 6.82 ± 0.92; P <.001), and 2 weeks (3.70 ± 0.89 versus 4.60 ± 1.03; P <.001) follow-up. Both outcomes became comparable from 4-week follow-up onward. Patient satisfaction (8.44 ± 1.68 versus 7.17 ± 1.04; P <.001) and additional non-steroidal anti-inflammatory drug consumption (2,770 ± 533.05 versus 3,566.04 ± 464.54; P <.001) were better in the duloxetine group, with a comparable safety profile. In patients who did not have CS, persistent pain after bilateral TKA can be managed safely and successfully by a daily dose of 20 mg Duloxetine, improving patient satisfaction and analgesic consumption in the acute postoperative phase. [ABSTRACT FROM AUTHOR]

Individuals with chronic pain due to knee osteoarthritis (OA) are insufficiently physically active, and alterations of facilitatory and inhibitory nociceptive signaling are common in this population. Our objective was to examine the association of these alterations in nociceptive signaling with objective accelerometer-based measures of physical activity in a large observational cohort. We used data from the Multicenter Osteoarthritis Study. Measures of peripheral and central pain sensitivity included pressure pain threshold at the knee and mechanical temporal summation at the wrist, respectively. The presence of descending pain inhibition was assessed by conditioned pain modulation (CPM). Physical activity was quantitatively assessed over 7 days using a lower back-worn activity monitor. Summary metrics included steps/day, activity intensity, and sedentary time. Linear regression analyses were used to evaluate the association of pain sensitivity and the presence of descending pain inhibition with physical activity measures. Data from 1873 participants was analyzed (55.9% female, age = 62.8 ± 10.0 years). People having greater peripheral and central sensitivity showed lower step counts. CPM was not significantly related to any of the physical activity measures, and none of the exposures were significantly related to sedentary time. In this cohort, greater peripheral and central sensitivity were associated with reduced levels of objectively-assessed daily step counts. Further research may investigate ways to modify or treat heightened pain sensitivity as a means to increase physical activity in older adults with knee OA. [ABSTRACT FROM AUTHOR]

Although the pathophysiology of fibromyalgia syndrome has been better understood in recent decades, a unified model of its pathogenesis and an effective therapeutic approach are still far from being realized. The main aim of this article will be to delve into the fundamental mechanisms of the pathophysiology of fibromyalgia conceptualized as stress intolerance syndrome. Using the biopsychosocial model of chronic pain syndromes, we will describe the potential role of the attachment system, C-tactile fibers, and oxytocinergic system dysfunction in the pathophysiology of fibromyalgia syndrome and other central sensitivity syndromes. At the end of the article, the therapeutic implications of this new global and translational pathophysiological model will be briefly discussed. [ABSTRACT FROM AUTHOR]

Posttraumatic headache (PTH) is common following traumatic brain injury and impacts quality of life. We investigated descending pain modulation as one possible mechanism for PTH and correlated it to clinical measures. Pain-related evoked potentials (PREP) were recorded in 26 PTH-patients and 20 controls after electrical stimulation at the right hand and forehead with concentric surface electrodes. Conditioned pain modulation (CPM) was assessed using painful cutaneous electric stimulation (PCES) on the right hand as test stimulus and immersion of the left hand into 10 °C-cold water bath as conditioning stimulus based on changes in pain intensity and in amplitudes of PCES-evoked potentials. All participants completed questionnaires assessing depression, anxiety, and pain catastrophising. PTH-patients reported significantly higher pain ratings during PREP-recording in both areas despite similar stimulus intensity at pain threshold. N1P1-amplitudes during PREP and CPM-assessment were lower in patients in both areas, but statistically significant only on the hand. Both, PREP-N1-latencies and CPM-effects (based on the N1P1-amplitudes and pain ratings) were similar in both groups. Patients showed significantly higher ratings for anxiety and depression, which did not correlate with the CPM-effect. Our results indicate generalized hyperalgesia for electrical stimuli in both hand and face in PTH. The lacking correlation between pain ratings and EEG parameters indicates different mechanisms of pain perception and nociception. [ABSTRACT FROM AUTHOR]

Background: Patients with vestibular migraine (VM) exhibit higher levels of central sensitization and share similar disorder characteristics with migraine with vestibular symptoms (MwVS), except in terms of disability. These patients experience fluctuating mechanical pain thresholds and persistent vestibular symptoms even without a migraine attack. Objective: This study aimed to investigate whether interictal allodynia or hyperalgesia can differentiate between VM, MwVS, and migraine only. Methods: We conducted a cross-sectional study of patients with episodic migraine aged between 18 and 65 years, categorized into three groups. A questionnaire was used to collect and compare demographic and clinical variables. Interictal widespread pressure hyperalgesia (IWPH) was evaluated using the Manual Tender Point Survey. Patients with tender point counts ≥7 were classified as having IWPH. Results: The study included 163 patients: 31 with VM, 54 with MwVS, and 78 with migraine without vestibular symptoms (migraine only). We found that aura (p = 0.042, odds ratio 3.50, 95% confidence interval 1.26-10.4), tender point count (p < 0.001, d = 0.889, median difference = 2), and IWPH (p = 0.002, odds ratio 5.3, 95% confidence interval 1.80-17.2) were significantly associated with VM compared to MwVS. Aura and IWPH were significantly associated with VM. However, there were no significant associations observed for interictal allodynia or hyperalgesia between the other two groups. Conclusion: IWPH and aura are associated with VM, indicating their potential roles in its pathogenesis. These findings may contribute to the differential diagnosis and management of migraine, potentially leading to targeted treatment strategies. [ABSTRACT FROM AUTHOR]

Clinical Scenario: Pain is a common symptom experienced by individuals who sustain an acute lateral ankle sprain and can continue to persist among those who develop chronic ankle instability. Most rehabilitation protocols for individuals with acute ankle sprains or chronic ankle instability focus on restoring physical impairments and have largely omitted any pain-relieving therapies. This impairment-based focus has led pain to be an understudied symptom among individuals with an ankle sprain history. Overlooking the role of pain has also left clinicians with little insight into whether pain experienced after an ankle sprain is local (i.e., peripheral sensitization) or widespread (i.e., central sensitization). Understanding the pain profiles for those with an ankle sprain history may represent an unexploited area for clinicians and future research to improve health outcomes for this patient population. Clinical Question: Is there evidence to suggest that pain mechanosensitivity levels are different between those with and without a history of lateral ankle sprain? Summary of Key Findings: The literature was systematically searched for Level 4 evidence or higher. The search yielded two cross-sectional case-control studies and one cross-sectional study that met the inclusion and exclusion criteria. Based on the available evidence, pain mechanosensitivity levels are lower across ligamentous stabilizers immediately after an acute ankle sprain and over lower extremity neuromuscular structures among individuals with chronic ankle instability. ClinicalBottom Line: There is weak evidence to support an ankle sprain history can affect local pain mechanosensitivity levels of structures surrounding the ankle but not at distant locations. Strength of Recommendation: Level 4 evidence is available according to the Center for Evidence-Based Medicine. [ABSTRACT FROM AUTHOR]

The insula and dorsal anterior cingulate cortex (dACC) are core brain regions involved in pain processing and central sensitization, a shared mechanism across various chronic pain conditions. Methods to modulate these regions may serve to reduce central sensitization, though it is unclear which target may be most efficacious for different measures of central sensitization. Objective/Hypothesis: Investigate the effect of low-intensity focused ultrasound (LIFU) to the anterior insula (AI), posterior insula (PI), or dACC on conditioned pain modulation (CPM) and temporal summation of pain (TSP). N = 16 volunteers underwent TSP and CPM pain tasks pre/post a 10 min LIFU intervention to either the AI, PI, dACC or Sham stimulation. Pain ratings were collected pre/post LIFU. Only LIFU to the PI significantly attenuated pain ratings during the TSP protocol. No effects were found for the CPM task for any of the LIFU targets. LIFU pressure modulated group means but did not affect overall group differences. LIFU to the PI reduced temporal summation of pain. This may, in part, be due to dosing (pressure) of LIFU. Inhibition of the PI with LIFU may be a future potential therapy in chronic pain populations demonstrating central sensitization. The minimal effective dose of LIFU for efficacious neuromodulation will help to translate LIFU for therapeutic options. • Low-intensity focused ultrasound (LIFU) can non-invasively target subregions of the insula and anterior cingulate. • LIFU to the posterior insula reduced pain ratings during temporal summation of pain but not conditioned pain modulation. • Estimated in vivo pressure varies across participants and brain targets and may help explain LIFU's effects. [ABSTRACT FROM AUTHOR]

Pain sensitivity is the main finding of central sensitization (CS) and can occur in patients with chronic shoulder pain. However, there is limited evidence concerning the distribution of pain sensitivity in shoulders, forearms, and legs in patients with CS associated with chronic shoulder pain. The present study aimed to determine the distribution of pain sensitivity in patients with CS associated with chronic subacromial pain syndrome (SPS). This cross-sectional study included 58 patients with chronic SPS and CS (patient group) and 58 healthy participants (control group). The presence of CS was determined using the Central Sensitization Inventory (CSI). To determine the distribution of pain sensitivity, pressure pain threshold (PPT) measurements were performed from the shoulders, forearms, and legs. There was no significant difference between the two groups in terms of sociodemographic data (p > 0.05). The patient group had a significantly higher CSI score (p < 0.001) and lower PPTs in all regions (p < 0.05) than the control group. Unlike the control group, the patient group had lower PPTs on the affected side for the shoulder [mean difference (MD) 95% confidence interval (CI): 1.2 (−1.7 to −0.6)], forearm [MD 95% CI: 1.1 (−1.7 to −0.6)], and leg [MD 95% CI: 0.9 (−1.4 to −0.3)] compared with the contralateral side (p < 0.001). Pain sensitivity is more pronounced in the affected shoulder and the forearm and leg located on this side than in those on the contralateral side in patients with CS associated with chronic SPS. • Pain sensitivity occurs in shoulders, forearms, and legs in patients with central sensitization associated with chronic subacromial pain syndrome. • Pain sensitivity is more pronounced in the forearm and leg on the side of the painful shoulder than in the symmetrical ones on the contralateral side. • The difference in pain pressure threshold between the distal and proximal regions is similar to that of healthy people. [ABSTRACT FROM AUTHOR]

Introduction: Aromatase inhibitor (AI)-induced musculoskeletal symptoms (AIMSS) can decrease health-related quality of life and lead to discontinuation of AI therapy for postmenopausal women with breast cancer (BC). Although central sensitization (CS) may contribute to AIMSS, the relevance of CS-related symptoms to AIMSS has not been fully clarified. This study aimed to investigate the relationship between AIMSS and CS-related symptoms in women with BC who received AI therapy. Methods: This cross-sectional study recruited women who underwent BC surgery before at least 1 year and were taking AI for at least 6 months. Participants were assessed for joint pain and CS-related symptoms using the central sensitization inventory (CSI). The severity of CS-related symptoms was classified into three groups, and the prevalence of AIMSS was calculated. Multiple logistic regression analysis was used to assess the relationship between AIMSS and factors of possible relevance to AIMSS, including CSI severity. Results: Of the 73 women who were included in this study, 31 (42.4%) were categorized into the AIMSS group and 42 (57.6%) into the non-AIMSS group. Participants with a history of chemotherapy and higher CSI score were significantly more likely to have AIMSS. Multiple logistic regression analysis showed that a history of chemotherapy (odds ratio = 4.21) and higher CSI severity (odds ratio = 13.43) had significantly associated with AIMSS. Conclusion: CS-related symptoms assessed using CSI may be strongly associated with AIMSS. Further longitudinal studies to investigate the causal relationship and effectiveness of CS-targeted interventions are needed to prevent and treat AIMSS effectively. [ABSTRACT FROM AUTHOR]

AbstractPurpose Based on a potential shared pathophysiology tied to mast cell activity and neurogenic inflammation that may link pruritus and chronic cough (CC), this study, leveraging the All of Us database, examines the association between the two conditions.Materials and methods A nested case-control comparison was used to examine the association, identifying cases with SNOMED codes 418363000 (pruritus) and 68154008 (CC). Matching was performed on a 1:4 ratio by age, sex, and ethnicity using the MatchIt package in R, followed by maximum likelihood method to estimate odds ratios (ORs) and 95% confidence intervals from 2x2 contingency tables.Results CC patients (n = 2,388) were more than twice as likely to be diagnosed with pruritus (OR: 2.65) and pruritus patients (n = 22,496) were more than twice as likely to be diagnosed with CC (OR: 2.57), than respective matched controls.Conclusions These results highlight the potential bidirectional relationship between CC and pruritus, suggesting possible shared immune and neural pathways. Treatments like difelikefalin and nalbuphine that modulate these pathways, alongside P2X3 targeting agents, are emerging as potential therapeutic approaches for itch and chronic cough given the possible interconnected pathophysiology. This study’s insights into the associations between pruritus and CC may pave the way for targeted therapeutic strategies that address their shared mechanisms.

Objectives: To investigate the presence and severity of central sensitization (CS) and its associations with clinical measures and quality of life (QoL) in individuals with a history of paralytic poliomyelitis with and without post-polio syndrome (PPS). Methods: In this cross-sectional study, we included 98 individuals with a history of poliomyelitis, in whom 82 (83.6%) met the criteria of PPS. We used CS Inventory (CSI) to evaluate the presence and severity of CS. We evaluated the severity of fatigue, pain, polio-related impairments, and QoL using a Numerical Rating Scale in addition to Fatigue Severity Scale, Self-reported Impairments in Persons with late effects of Polio rating scale (SIPP), and Nottingham Health Profile (NHP). Results: CS was present in 52.4% of patients with PPS, of which 63% are classified as severe to extreme. Those with CS reported more severe symptoms, more polio-related impairments, and worse QoL than those without CS. Severity of CS showed significant positive correlations with severity of fatigue, pain, SIPP, and NHP scales in those with PPS. CSI did not indicate CS in any of those without PPS. Conclusion: CS was present in more than half of the individuals with PPS and correlated with more severe pain, fatigue, and more polio-related impairments, in addition to poorer QoL. These findings suggest that CS may contribute to the clinical picture in a subgroup of individuals with PPS. Thus, identification and appropriate management of CS patients may potentially help alleviate their symptoms and improve their QoL.

Relevance. The phenomenon of central sensitization occurs when physiological activity in nociceptive pathways increases and leads to abnormal sensitivity; it is defined as “increased sensitivity of nociceptive neurons of the central nervous system to their normal or subthreshold afferent input,” according to the definition provided by the International Association for the Study of Pain (IASP). The excitability of spinal cord neurons significantly modifies the gain of the somatosensory system. Chronic pain syndromes, anxiety-depressive disorder, sleep disorders are currently very common in the population, significantly reducing the quality of life of the population; the pathogenesis of these nosologies lies in central sensitization. Objective. To study the clinical manifestations of central sensitization in patients with episodic migraine associated with neck pain or cervicogenic headache. Materials and methods. The longitudinal prospective study included 180 patients, divided into 3 groups: 1) patients with a combination of migraine and cervicogenic headache – 60 people (study group); 2) patients with a combination of migraine and cervicalgia diagnoses – 60 people (control group); 3) patients diagnosed with migraine without complaints of pain and limitation of movements in the cervical spine – 60 people (additional group). Results. In patients with migraine and comorbid cervical headache, more pronounced central sensitization was revealed when compared with comorbid cervicalgia. Myofascial pain syndrome involving the trapezius and temporal muscles can resolve on its own with specific migraine therapy with monoclonal antibodies, however, to relieve tension and soreness in the masseter and inferior oblique muscles, the addition of therapeutic exercises and gentle manual techniques is more effective. Taking into account the identified direct relationships of moderate strength between the number of painful points of exit of the trigeminal nerve, the muscles of the pericranial region involved, as well as the effect of treatment of migraine attacks with monoclonal antibodies, it can be concluded that central sensitization is more pronounced when the masseter and inferior oblique muscles are involved. Conclusions. During examination of patients with migraine with comorbid active cervicalgic factor or even if it is absence, it is necessary to make a thorough examination of the facial and cranioverebral region muscles, even in the absence of patient complaints of pain in the face or neck, and also prescribe specific therapeutic exercises to increase the effectiveness of treatment. In all patients with migraine, regardless of chronicity, it is necessary to assess the intensity of central sensitization for timely and more complete provision of medical care.

Abstract Introduction Chronic neck pain (CNP) is a global public health problem, with high prevalence and absenteeism rates. Central sensitization (CS) as a basis for chronic pain may play an essential role in its development and progression. It is often comorbid with low conditioned pain modulation (CPM) effects, cognitions, and psychological problems. Objectives The purposes of this study were to (1) explore the relationship between pain-related cognitions and psychological factors, CPM effects, and the central sensitization inventory (CSI) scores; and (2) determine whether cognitions and psychological factors can predict CSI scores and CPM effects in individuals with CNP. Methods Fifty-four individuals with CNP were recruited for this cross-sectional study. The following outcome measures were evaluated: The CSI (screening tool) was compared with the cold pressor test (CPT), which was the psychophysical test used to assess the CPM; neck pain intensity using the visual analogue scale (VAS), as well as pain-related cognitions (including kinesiophobia and pain catastrophization) and psychological states (including anxiety and depression) using self-report questionnaires. Results CSI score was not associated with the CPM effect (r = 0.257, p > 0.05), and no cognitions or psychological factors were associated with CPM (p > 0.05), but CSI score was moderately positively correlated with kinesiophobia (r = 0.554, p

Rani Othman, Abdulrahman Mohammed Bajaber, Anas Mohammed Alhabshi, Majed Albadi, Rawan Aldhabi, Muataz Almaddah, Abdullah Alqarni Physical Therapy Department, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Rani Othman, Email rhothman@kau.edu.saBackground: Central sensitization (CS) has been proposed as a possible contributor to persistent shoulder pain. Measures of sensitivity, such as quantitative sensory tests (QSTs) and sensitivity to movements evoked pain (SMEP), have been increasingly used to investigate CS in a wide range of painful conditions. However, there is a lack of data on whether QST and SMEP are reliable among individuals with shoulder pain. Therefore, the present study aimed to investigate the intra-rater test–retest reliability of QST and SMEP in individuals with chronic shoulder pain.Materials and Methods: Forty-seven individuals with chronic shoulder pain were enrolled in the study. The QST measures, including pressure pain threshold (PPT) and mechanical temporal summation (MTS), were tested, and SMEP was measured with a lifting task. Relative and absolute reliability were analyzed using intraclass correlation coefficients (ICC 3,1) and standard error of the measurement (SEM), respectively.Results: The results showed that the ICC coefficients for all sensitivity measures were moderate to good, ranging from 0.63 to 0.86. The SEM% for the QST measures at all sites ranged from 21.4% to 36%, with TS at the forearm demonstrating a high SEM% (greater than 30%). The SMEP measure also showed a high SEM% (46%).Conclusion: The results showed that the sensitivity measures had moderate to good reliability among individuals with shoulder pain. Acceptable limits of accuracy of measurements were demonstrated for TS and PPT measures, while SMEP demonstrated high error, highlighting the need for further refinement of this measure among these populations.Keywords: shoulder pain, quantitative sensory testing, sensitive to movement evoked pain, central sensitization, reliability