Programa de Pós-graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil; Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil; Escola de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Behav Brain Res. 2021 Aug 27;412:113439. doi: 10.1016/j.bbr.2021.113439. Epub 2021 Jun 29.
Menopause is related to a decline in ovarian oestrogen production, affecting the perception of the somatosensory stimuli, changing the immune-inflammatory systems, and triggering depressive symptoms. It has been demonstrated that the inhibition of the kinin B and B receptors (BR and BR) prevented the depressive-like behaviour and the mechanical allodynia that was induced by immune-inflammatory mediators in mice. However, there is no evidence regarding the role of the kinin receptors in the depressive-like and nociceptive behaviour in female mice that were subjected to bilateral ovariectomy (OVX). This study has shown that the OVX mice developed time-related mechanical allodynia, together with an increased immobility time as indicative of depression. Both of these changes were reduced by the genetic deletion of BR, or by the pharmacological blockade of the selective kinin BR antagonist R-715 (acute, i.p.). The genetic deletion or the pharmacological inhibition of BR (HOE 140, i.p.) did not prevent the OVX-elicited behavioural changes. The data has suggested a particular modulation of kinin BR in the nociceptive and depressive-like behaviour in the OVX mice. The selective inhibition of the BR receptor may be a new pharmacological target for treating pain and depression symptoms in women during the perimenopause/menopause period.
绝经与卵巢雌激素产生减少有关，影响躯体感觉刺激的感知，改变免疫炎症系统，并引发抑郁症状。已经证明，激肽 B 和 B 受体（BR 和 BR）的抑制可以预防免疫炎症介质在小鼠中引起的类似抑郁的行为和机械性痛觉过敏。然而，关于激肽受体在双侧卵巢切除（OVX）的雌性小鼠中类似抑郁和伤害感受行为中的作用，尚无证据。本研究表明，OVX 小鼠出现了与时间相关的机械性痛觉过敏，并表现出更多的不动时间，表明出现了抑郁。BR 的基因缺失或选择性激肽 BR 拮抗剂 R-715（急性，腹腔内给药）的药理学阻断均可减轻这两种变化。BR 的基因缺失或药理学抑制（HOE 140，腹腔内给药）并不能预防 OVX 引起的行为变化。这些数据表明，激肽 BR 在 OVX 小鼠的伤害感受和类似抑郁行为中存在特定的调节作用。选择性抑制 BR 受体可能成为治疗围绝经期/绝经后妇女疼痛和抑郁症状的新的药理学靶点。
