Laboratory of Pain Research, Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic.
Department of Anaesthesiology, Resuscitation and Critical Care, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague, Czech Republic.
Int J Mol Sci. 2021 Apr 2;22(7):3712. doi: 10.3390/ijms22073712.
Transient receptor potential vanilloid 1 (TRPV1) channels contribute to the development of several chronic pain states and represent a possible therapeutic target in many painful disease treatment. Proinflammatory mediator bradykinin (BK) sensitizes TRPV1, whereas noxious peripheral stimulation increases BK level in the spinal cord. Here, we investigated the involvement of spinal TRPV1 in thermal and mechanical hypersensitivity, evoked by intrathecal (i.t.) administration of BK and an endogenous agonist of TRPV1, N-oleoyldopamine (OLDA), using behavioral tests and i.t. catheter implantation, and administration of BK-induced transient thermal and mechanical hyperalgesia and mechanical allodynia. All these hypersensitive states were enhanced by co-administration of a low dose of OLDA (0.42 µg i.t.), which was ineffective only under the control conditions. Intrathecal pretreatment with TRPV1 selective antagonist SB366791 prevented hypersensitivity induced by i.t. co-administration of BK and OLDA. Our results demonstrate that both thermal and mechanical hypersensitivity evoked by co-administration of BK and OLDA is mediated by the activation of spinal TRPV1 channels.
瞬时受体电位香草酸 1 型（TRPV1）通道参与多种慢性疼痛状态的发展，是许多疼痛性疾病治疗的潜在治疗靶点。促炎介质缓激肽（BK）敏化 TRPV1，而有害的外周刺激会增加脊髓中的 BK 水平。在这里，我们通过行为测试和鞘内导管植入以及鞘内给予 BK 诱导的短暂热和机械痛觉过敏和机械性痛觉过敏，研究了脊髓 TRPV1 对 BK 和 TRPV1 的内源性激动剂 N-油酰多巴胺（OLDA）鞘内给药引起的热和机械敏感性的参与。使用行为测试和鞘内导管植入以及鞘内给予 BK 诱导的短暂热和机械痛觉过敏和机械性痛觉过敏，研究了脊髓 TRPV1 对 BK 和 TRPV1 的内源性激动剂 N-油酰多巴胺（OLDA）鞘内给药引起的热和机械敏感性的参与。使用行为测试和鞘内导管植入以及鞘内给予 BK 诱导的短暂热和机械痛觉过敏和机械性痛觉过敏，研究了脊髓 TRPV1 对 BK 和 TRPV1 的内源性激动剂 N-油酰多巴胺（OLDA）鞘内给药引起的热和机械敏感性的参与。所有这些超敏状态都通过鞘内共同给予低剂量 OLDA（0.42μg 鞘内）增强，而在对照条件下无效。TRPV1 选择性拮抗剂 SB366791 鞘内预处理可预防 BK 和 OLDA 鞘内共同给药引起的超敏反应。我们的结果表明，BK 和 OLDA 共同给药引起的热和机械超敏反应是由脊髓 TRPV1 通道的激活介导的。
