Sex differences in the affective-cognitive dimension of neuropathic pain: Insights from the spared nerve injury rat model

IF 4 2区医学 Q1 CLINICAL NEUROLOGY

Journal of Pain Pub Date : 2025-02-01 DOI:10.1016/j.jpain.2024.104752

Laura Boullon , David P. Finn , Álvaro Llorente-Berzal

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引用次数: 0

Abstract

Over 40% of neuropathic pain patients experience mood and cognitive disturbances, often showing reduced response to analgesics, with most affected individuals being female. This highlights the critical role of biological sex in pain-related affective and cognitive disorders, making it essential to understand the emotional and cognitive circuits linked to pain for improving treatment strategies. However, research on sex differences in preclinical pain models is lacking. This study aimed to investigate these differences using the spared nerve injury (SNI) rat model, conducting a comprehensive series of behavioural tests over 100 days post-injury to identify key time points for observing sex-specific behaviours indicative of pain-related conditions. The findings revealed that female rats exhibited greater mechanical and cold hypersensitivity compared to males following nerve injury and showed earlier onset of depression-related behaviours, while males were more prone to anxiety, social, and memory-related alterations. Interestingly, by the 14th week post-injury, females displayed no signs of these emotional and cognitive impairments. Additionally, fluctuations in the oestrous cycle or changes in testosterone and oestradiol levels did not correlate with sex differences in pain sensitivity or negative affect. Recognizing the influence of biological sex on pain-induced affective and cognitive alterations, especially in later stages post-injury, is crucial for enhancing our understanding of this complex pain disorder.

Perspective

This manuscript reports the relevance of long-term investigations of sex differences in chronic pain. It shows differential development of somatosensory sensitivity, negative affective states and cognitive impairments in males and females. It emphasizes the importance of including subjects of both sexes in the investigation of pain-related mechanisms and therapeutic management.

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神经性疼痛的情感-认知维度的性别差异：来自神经损伤大鼠模型的见解。

超过40%的神经性疼痛患者会出现情绪和认知障碍，通常对镇痛药反应降低，其中大多数患者为女性。这凸显了生理性别在疼痛相关的情感和认知障碍中的关键作用，因此了解与疼痛相关的情感和认知回路对于改善治疗策略至关重要。然而，缺乏关于临床前疼痛模型性别差异的研究。本研究旨在利用SNI大鼠模型研究这些差异，在损伤后100天进行一系列全面的行为测试，以确定观察与疼痛相关的性别特异性行为的关键时间点。研究结果显示，与雄性相比，雌性大鼠在神经损伤后表现出更大的机械和冷超敏反应，并表现出更早的抑郁相关行为，而雄性大鼠更容易出现焦虑、社交和记忆相关的改变。有趣的是，在受伤后的第14周，雌性没有表现出这些情绪和认知障碍的迹象。此外，发情周期的波动或睾酮和雌二醇水平的变化与疼痛敏感性或负面影响的性别差异无关。认识到生理性别对疼痛引起的情感和认知改变的影响，特别是在损伤后的后期阶段，对于增强我们对这种复杂疼痛障碍的理解至关重要。数据可用性：可以从该出版物的通讯作者处请求访问构成本文中提出的发现的原始数据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pain 医学-临床神经学

CiteScore

6.30

自引率

7.50%

发文量

441

审稿时长

42 days

期刊介绍： The Journal of Pain publishes original articles related to all aspects of pain, including clinical and basic research, patient care, education, and health policy. Articles selected for publication in the Journal are most commonly reports of original clinical research or reports of original basic research. In addition, invited critical reviews, including meta analyses of drugs for pain management, invited commentaries on reviews, and exceptional case studies are published in the Journal. The mission of the Journal is to improve the care of patients in pain by providing a forum for clinical researchers, basic scientists, clinicians, and other health professionals to publish original research.