The expression of hormonal receptors in pain-processing regions complicates understanding the hormonal effects on pain mechanisms. This study investigates androgen receptor (AR) involvement in pain sensitivity and sex differences in pain perception. Mechanical pain thresholds were higher in normal male mice compared to gonadectomized (GDX) male and normal female mice, correlating with serum testosterone levels. In the dorsal root ganglia (DRG), AR was expressed in normal males but undetectable in GDX males and normal females. Androgen receptor overlapped with NeuN, a neuronal nuclei marker, indicating androgen signaling activation in sensory neurons. In male sensory neuron–selective AR conditional knockout (AR-cKO) mice, mechanical pain thresholds were significantly lower than in wild-type males, with the greatest AR depletion in calcitonin gene–related peptide (CGRP) ⁺ neurons. Electrophysiological analyses revealed increased excitability of spinal dorsal horn neurons in both GDX males and AR-cKO males. In female mice, administration of testosterone propionate or dihydrotestosterone significantly raised mechanical pain thresholds, accompanied by increased AR expression in the DRG. This effect was abolished in AR-cKO females, where AR depletion was most prominent in CGRP ⁺ neurons, consistent with male findings. These results indicate that primary sensory neurons, particularly CGRP ⁺ neurons, are critical targets of androgen in regulating mechanical pain sensitivity. Therefore, manipulating androgen signaling in sensory neurons may offer a promising approach to managing mechanical pain.

It is well‐established that spinal microglia and peripheral macrophages play critical roles in the etiology of neuropathic pain; however, growing evidence suggests sex differences in pain hypersensitivity owing to microglia and macrophages. Therefore, it is crucial to understand sex‐ and androgen‐dependent characteristics of pain‐related myeloid cells in mice with nerve injury‐induced neuropathic pain. To deplete microglia and macrophages, pexidartinib (PLX3397), an inhibitor of the colony‐stimulating factor 1 receptor, was orally administered, and mice were subjected to partial sciatic nerve ligation (PSL). Following PSL induction, healthy male and female mice and male gonadectomized (GDX) mice exhibited similar levels of spinal microglial activation, peripheral macrophage accumulation, and mechanical allodynia. Treatment with PLX3397 significantly suppressed mechanical allodynia in normal males; this was not observed in female and GDX male mice. Sex‐ and androgen‐dependent differences in the PLX3397‐mediated preventive effects were observed on spinal microglia and dorsal root ganglia (DRG) macrophages, as well as in expression patterns of pain‐related inflammatory mediators in these cells. Conversely, no sex‐ or androgen‐dependent differences were detected in sciatic nerve macrophages, and inhibition of peripheral CC‐chemokine receptor 5 prevented neuropathic pain in both sexes. Collectively, these findings demonstrate the presence of considerable sex‐ and androgen‐dependent differences in the etiology of neuropathic pain in spinal microglia and DRG macrophages but not in sciatic nerve macrophages. Given that the mechanisms of neuropathic pain may differ among experimental models and clinical conditions, accumulating several lines of evidence is crucial to comprehensively clarifying the sex‐dependent regulatory mechanisms of pain.

The quality of clinical practice guidelines (CPGs) should be extensively evaluated. This study aimed to evaluate Japanese CPGs that include recommendations for acupuncture. In a literature search, CPGs including recommendations for acupuncture published in Japan until October 2021 were sought. We assessed (1) whether the CPGs were developed in accordance with the Grading Recommendations Assessment, Development and Evaluation (GRADE) system, (2) the quality of the CPGs using the Appraisal of Guidelines for Research and Evaluation (AGREE) II, and (3) whether the strength of the recommendations for acupuncture was consistent with each CPG's predefined procedure. Seventeen CPGs including 23 recommendations in total were identified and assessed. (1) Three CPGs were in accordance with the GRADE system. (2) The mean score of overall assessment using AGREE II was 4.5 on a 7-point Likert scale. The mean domain scores were 77% for domain 1 (scope and purpose), 54% for domain 2 (stakeholder involvement), 48% for domain 3 (rigor of development), 78% for domain 4 (clarity of presentation), 20% for domain 5 (applicability), and 51% for domain 6 (editorial independence). (3) The strength of the recommendations for acupuncture in two CPGs was judged to be underestimated. Some of the CPGs contained elementary problems that were not considered in AGREE II. The methodological quality of Japanese CPGs including recommendations for acupuncture was not necessarily high. Since technical issues exist in each field of therapy, the respective experts should be involved in developing and reviewing CPGs to disseminate accurate health information.

Recent studies have revealed marked sex differences in pathophysiological roles of spinal microglia in neuropathic pain, with microglia contributing to pain exacerbation exclusively in males. However, the characteristics of pain-enhancing microglia, which are more prominent in males, remain poorly understood. Here, we reanalyzed a previously published single-cell RNA sequencing dataset and identified a microglial subpopulation that significantly increases in the spinal dorsal horn (SDH) of male mice following peripheral nerve injury. CC-chemokine ligand 4 (CCL4) was highly expressed in this subpopulation and its mRNA levels were increased in the SDH after partial sciatic nerve ligation (PSL) only in male mice. Notably, CCL4 expression was reduced in male mice following microglial depletion, indicating that microglia are the primary source of CCL4. Intrathecal administration of maraviroc, an inhibitor of the CCL4–CC-chemokine receptor 5 (CCR5) signaling pathway, after PSL, significantly suppressed mechanical allodynia only in male mice. Furthermore, intrathecal administration of CCL4 induced mechanical allodynia in both sexes, accompanied by increased expression of c-fos, a neuronal excitation marker, in the SDH. These findings highlight a sex-biased difference in the gene expression profile of spinal microglia following peripheral nerve injury, with elevated CCL4 expression in male mice potentially contributing to pain exacerbation.

オランダで開催予定であった2020年の世界鍼灸学会連合会(WFAS)年次大会は、新型コロナウイルス感染症の世界的な感染拡大のため中止となり、11月28日、29日に中国・海南省海口市においてその代替大会が開催された。今回の大会の最大の特徴は、on-siteとonlineでのハイブリッド形式での初めての開催にある。28日の夕方に開かれた執行理事会では、59名もの執行理事が顔をそろえ報告や審議が行われた。前回のトルコでの執行理事会においてJSAMが提案し承認された、WFAS倫理綱領へのヘルシンキ宣言の追加について1年あまり進展がないため、再度の提案を行った。本稿では、執行理事会における報告および審議事項に関する概要の報告と、同日に開催された標準化委員会での診療ガイドライン策定に関連する講演の内容を紹介する。