Boullon Laura, Finn David P, Llorente-Berzal Álvaro
Pharmacology and Therapeutics, School of Medicine, Human Biology Building, University of Galway, Galway, Ireland; Galway Neuroscience Centre, University of Galway, Galway, Ireland; Centre for Pain Research, University of Galway, Galway, Ireland.
Pharmacology and Therapeutics, School of Medicine, Human Biology Building, University of Galway, Galway, Ireland; Galway Neuroscience Centre, University of Galway, Galway, Ireland; Centre for Pain Research, University of Galway, Galway, Ireland; Department of Physiology, School of Medicine, Autonomous University of Madrid, Madrid, Spain.
J Pain. 2025 Feb;27:104752. doi: 10.1016/j.jpain.2024.104752. Epub 2024 Dec 1.
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.
超过40%的神经性疼痛患者会出现情绪和认知障碍，通常对镇痛药的反应降低，其中受影响最严重的是女性。这凸显了生物性别在疼痛相关的情感和认知障碍中的关键作用，因此有必要了解与疼痛相关的情绪和认知回路，以改进治疗策略。然而，临床前疼痛模型中关于性别差异的研究尚缺。本研究旨在使用 spared nerve injury (SNI) 大鼠模型调查这些差异，在损伤后100天内进行一系列全面的行为测试，以确定观察与疼痛相关状况的性别特异性行为的关键时间点。研究结果显示，与雄性大鼠相比，雌性大鼠在神经损伤后表现出更高的机械性和冷敏性，并更早出现与抑郁相关的行为，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，在损伤后第14周，雌性大鼠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。认识到生物性别对疼痛引起的情感和认知改变的影响，尤其是在损伤后期，对于加深我们对这种复杂疼痛障碍的理解至关重要。观点：本手稿报告了慢性疼痛中性别差异长期研究的相关性。它显示了男性和女性在体感敏感性、负面情绪状态和认知障碍方面的不同发展。它强调在疼痛相关机制和治疗管理的研究中纳入两性受试者的重要性。
