Chronic neuropathic pain affects 7–10 % of the population and is often accompanied by comorbid emotional disorders, which greatly reduce the quality of life of the patients, impairing physical, cognitive, emotional, and social functioning. Despite the higher prevalence and severity of chronic pain in women, the number of publications using female animals remains scarce. While in the chronic constriction injury (CCI) model the development of mechanical/thermal hyperalgesia, allodynia and spontaneous pain has been shown in both sexes, little is known on CCI-induced emotional impairments and sciatic nerve histopathology in female rats, as well as on the contributions of ovarian hormones to peripheral nerve injury.

In this work, young adult rats (Wistar Han) were assigned to one of five groups: gonadally intact females (SHAM/SHAM), ovariectomized females (SHAM/OVX), gonadally intact females with CCI (CCI/SHAM); ovariectomized females with CCI (CCI/OVX) and males with CCI (CCI_M). In the postoperative period, CCI animals, both females and males, displayed visible gait abnormalities, limping and guarding the affected hind paw although locomotion was not affected. Neuropathic females developed sustained mechanical allodynia, with CCI/OVX animals displaying symptoms two weeks before CCI/SHAM females. Interestingly, regarding mechanical and cold allodynia, CCI males slowly recovered from week 3 onwards. While CCI induced neither anxiety- nor depressive-like behaviour in females, ovariectomy per se induced anhedonic-like behaviour, regardless of CCI surgery. Histopathological analysis of the sciatic nerve showed CCI induced nerve damage, fibrosis, myelin sheath degradation and inflammation. Single-cell electrophysiological data from the rostral ventromedial medulla (RVM) suggests this area is partly involved in descending facilitation associated with experimental neuropathic pain. Altogether, our findings demonstrate CCI females display distinct sensory, emotional, electrophysiological, and histopathological impairments from males, and that ovariectomy aggravates females’ responses to peripheral nerve injury.

慢性神经性疼痛影响 7% 至 10% 的人口，并常伴有情绪障碍，极大地降低患者的生活质量，损害身体、认知、情绪和社会功能。尽管女性慢性疼痛的患病率和严重程度更高，但使用雌性动物的出版物数量仍然很少。虽然在慢性缩窄性损伤 (CCI) 模型中，两性都显示了机械/热痛觉过敏、异常性疼痛和自发性疼痛的发展，但对 CCI 诱导的雌性大鼠的情绪障碍和坐骨神经组织病理学知之甚少，以及卵巢激素对周围神经损伤的贡献。

在这项工作中，年轻的成年大鼠 (Wistar Han) 被分配到五组之一：性腺完整的雌性 (SHAM/SHAM)、卵巢切除的雌性 (SHAM/OVX)、性腺完整的 CCI 雌性 (CCI/SHAM)；卵巢切除的 CCI 女性 (CCI/OVX) 和男性 CCI (CCI _M )。在术后期间，CCI 动物，无论是雌性还是雄性，都表现出明显的步态异常，一瘸一拐并保护受影响的后爪，尽管运动没有受到影响。神经性雌性出现持续的机械性异常性疼痛，CCI/OVX 动物在 CCI/SHAM 雌性出现前两周出现症状。有趣的是，关于机械性和冷性异常性疼痛，CCI 雄性从第 3 周开始慢慢恢复。虽然 CCI 不会在女性中引起类似焦虑或抑郁的行为，但卵巢切除术本身无论 CCI 手术如何，都会诱发快感缺失样行为。坐骨神经的组织病理学分析显示 CCI 诱导的神经损伤、纤维化、髓鞘降解和炎症。来自延髓头端腹内侧 (RVM) 的单细胞电生理数据表明，该区域部分参与了与实验性神经性疼痛相关的下行促进作用。总而言之，我们的研究结果表明 CCI 女性表现出与男性不同的感觉、情绪、电生理和组织病理学损伤，并且卵巢切除术会加剧女性对周围神经损伤的反应。