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Neuropathic pain (NP) is the cardinal symptom of neural injury, and its underlying molecular mechanism needs further investigation. Complements, especially complement 3 (C3), are involved in the pathophysiology of many neurological disorders, while the specific role of C3 in NP is still obscure. In this study, we found that both C3 and its receptor C3aR were upregulated in the spinal dorsal horn in a rat chronic constriction injury (CCI) model. In addition, C3 was mainly detected in astrocytes, while C3aR was expressed in microglia and neuron. Intrathecal injection of C3 antibody and C3aR antagonist alleviated NP in CCI model together with reduced M1 polarization of microglia. Our finding suggested that blockade of the C3/C3aR pathway might be a novel strategy for NP.

To examine the association between chronic spontaneous urticaria (CSU) and interstitial cystitis/bladder pain syndrome (IC/BPS).

Early diagnosis and treatment of endometriosis affecting adolescent women are important in preventing chronic pain. Our aim was to analyze the clinical characteristics and severity of symptoms in adolescent patients with endometriosis compared to older patients.

GLIMMER assessed dose-response, efficacy, and safety of linerixibat, an ileal bile acid transporter inhibitor in development for cholestatic pruritus associated with primary biliary cholangitis (PBC).

Accurately identifying high-need, high-cost (HNHC) patients to reduce their preventable or modifiable health care use for their chronic conditions is a priority and a challenge for U.S. policymakers, health care delivery systems, and payers.

Peripheral nerve injury sensitizes a complex network of spinal cord dorsal horn (DH) neurons to produce allodynia and neuropathic pain. The identification of a druggable target within this network has remained elusive, but a promising candidate is the neuropeptide Y (NPY) Y1 receptor-expressing interneuron (Y1-IN) population. We report that spared nerve injury (SNI) enhanced the excitability of Y1-INs and elicited allodynia (mechanical and cold hypersensitivity) and affective pain. Similarly, chemogenetic or optogenetic activation of Y1-INs in uninjured mice elicited behavioral signs of spontaneous, allodynic, and affective pain. SNI-induced allodynia was reduced by chemogenetic inhibition of Y1-INs, or intrathecal administration of a Y1-selective agonist. Conditional deletion of in DH neurons, but not peripheral afferent neurons prevented the anti-hyperalgesic effects of the intrathecal Y1 agonist. We conclude that spinal Y1-INs are necessary and sufficient for the behavioral symptoms of neuropathic pain and represent a promising target for future pharmacotherapeutic development of Y1 agonists.

To investigate experiences and reflections on challenges in everyday life of people living with limb-girdle muscular dystrophy (LGMD) and chronic pain in order to improve rehabilitation services.

The importance of pain education is widely accepted and recognized. This is a key part of educating the undergraduate and postgraduate healthcare workforce is an essential strategy for promoting effective pain practice. This study aims to evaluate the pain management module training courses for newly graduated doctors to address the knowledge gap between specialist care and primary care physicians. This was an observational study of an evaluation of a pain education project focused on neuropathic pain management core competency was provided. Multimodal teaching approaches such as didactic teaching and vignettes of cases discussion, video teaching, and learning module. A pretest survey was carried out to assess the baseline knowledge of the participants. Completion of the post-test and participant experience questionnaire were collected. Comparison of the pre-and post-test scores for all participants was undertaken using the Wilcoxon signed-ranked test with effect size calculated. The participant's experience questionnaire scores were analyzed descriptively to produce mean and standard deviations from each question. A total of 274 participants completed all of the course sections from the average of 350 eligible participants. Of 274 participants, more than half were female (64.96%), with more than half participants being General Practitioner (54.38%) followed by a neurologist (35.04%). For all sessions, a Wilcoxon signed-rank test outlined that differences between all pre-and post-test scores were significant (P < .001). There was a marked improvement in the post-test as evidenced by statistically significant increases in mean scores differences. We developed an educational training courses for physicians to address the limitation in existing medical undergraduate training of neuropathic pain management. The training led to improvement in participant's knowledge and skills with positive outcomes.

Good clinical outcomes in orthopaedics are largely dictated by the biomedical model, despite mounting evidence of the role of psychosocial factors. Understanding orthopaedic providers' conceptualizations of good clinical outcomes and what facilitates and hinders them may highlight critical barriers and opportunities for training providers on biopsychosocial models of care and integrating them into practice.

The rostral ventromedial medulla (RVM) exerts bi-directional descending modulation of pain, attributable to the activity of electrophysiologically-identified pro-nociceptive ON and anti-nociceptive OFF neurons. Here we report that GABAergic ON neurons specifically express G protein-coupled estrogen receptor (GPER). GPER+ neurons exhibited characteristic ON-like responses upon peripheral nociceptive stimulation. Optogenetic activation of GPER+ neurons facilitated, whilst their ablation abrogated pain. Furthermore, activation of GPER caused depolarization of ON cells, potentiated pain and ameliorated morphine analgesia through desensitizing μ-type opioid receptor (MOR)-mediated activation of potassium currents. In contrast, genetic ablation or pharmacological blockade of GPER attenuated pain, enhanced morphine analgesia and delayed the development of morphine tolerance in diverse preclinical pain models. Our data strongly support GPER as a marker for GABAergic ON cells and also illuminate the mechanisms underlying hormonal regulation of pain and analgesia, highlighting GPER as a promising target for the treatment of pain and opioid tolerance.