Zaheer Fariya, Levine Gabriel J, Simal Ana Leticia, Fatemi Tabatabaei Seyed Reza, Martino Tami A, Descalzi Giannina
Department of Biomedical Sciences, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Center for Cardiovascular Investigations, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
eNeuro. 2025 Feb 3;12(2). doi: 10.1523/ENEURO.0244-24.2024. Print 2025 Feb.
Chronic pain is a debilitative disease affecting one in five adults globally and is a major risk factor for anxiety ( Goldberg and McGee, 2011; Lurie, 2018). Given the current dearth of available treatments for both individuals living with chronic pain and mental illnesses, there is a critical need for research into the molecular mechanisms involved in order to discover novel treatment targets. Cellular homeostasis is crucial for normal bodily functions, and investigations of this process may provide better understanding of the mechanisms driving the development of chronic pain. Using the spared nerve injury (SNI) model of neuropathic pain, we found contrasting roles for BECLIN-1 in the development of pain hypersensitivity and anxiety-like behaviors in a sex-dependent manner. Remarkably, we found that male SNI mice with impaired BECLIN-1 function demonstrated heightened mechanical and thermal hypersensitivity compared with male wild-type SNI mice, while female SNI mice with impaired BECLIN-1 function demonstrated similar thresholds to the female wild-type SNI mice. We also found that disruptions of BECLIN-1 prevented SNI-induced increases in anxiety-like behaviors in male mice. Our data thus indicate that BECLIN-1 is differentially involved in the nociceptive and emotional components of chronic pain in male but not female mice.
慢性疼痛是一种使人衰弱的疾病，全球五分之一的成年人受其影响，并且是焦虑的主要风险因素（戈德堡和麦吉，2011年；卢里，2018年）。鉴于目前针对慢性疼痛患者和精神疾病患者的可用治疗方法匮乏，迫切需要对其中涉及的分子机制进行研究，以便发现新的治疗靶点。细胞稳态对于正常身体功能至关重要，对这一过程的研究可能有助于更好地理解驱动慢性疼痛发展的机制。利用神经性疼痛的 spared nerve injury（SNI）模型，我们发现 BECLIN-1 在疼痛超敏反应和焦虑样行为的发展中以性别依赖的方式发挥着相反的作用。值得注意的是，我们发现 BECLIN-1 功能受损的雄性 SNI 小鼠与雄性野生型 SNI 小鼠相比，表现出更高的机械性和热超敏反应，而 BECLIN-1 功能受损的雌性 SNI 小鼠与雌性野生型 SNI 小鼠表现出相似的阈值。我们还发现，BECLIN-1 的破坏可防止 SNI 诱导的雄性小鼠焦虑样行为增加。因此，我们的数据表明，BECLIN-1 在雄性而非雌性小鼠慢性疼痛的伤害感受和情绪成分中发挥着不同的作用。
