Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Neuropeptides. 2010 Apr;44(2):87-92. doi: 10.1016/j.npep.2009.10.005. Epub 2009 Nov 14.
Mechanisms coupled to kinin B(1) and B(2) receptors have been implicated in sensory changes associated to various models of neuropathy. The current study aimed to investigate if kinins also participate in orofacial thermal hyperalgesia induced by constriction of the infraorbital nerve (CION), a model of trigeminal neuropathic pain which displays persistent hypersensitivity to orofacial sensory stimulation, in rats and mice. Male Swiss mice (30-35g) or Wistar rats (200-250g; n=6-10 per group in both cases) underwent CION or sham surgery and were submitted repeatedly to application of heat ( approximately 50 degrees C) to the ipsilateral or contralateral snout, delivered by a heat source placed 1cm from the vibrissal pad. Decreases in latency to display head withdrawal or vigorous snout flicking were considered indicative of heat hyperalgesia. CION caused long-lasting heat hyperalgesia which started on Day 2 after surgery in both species and lasted up to Day 17 in mice and Day 10 in rats. Administration of DALBK or HOE-140 (peptidic B(1) and B(2) receptor antagonists, respectively; each at 3nmol in 10microl) onto the exposed infraorbital nerve of mice at the moment of surgery delayed the development of the thermal hyperalgesia. Systemic treatment on Day 5 (mice) or Day 4 (rats) with Des-Arg(9), Leu(8)-Bradykinin (DALBK, B(1) receptor antagonist, 0.1-1micromol/kg, i.p.) or HOE-140 (B(2) receptor antagonist, 0.001-1micromol/kg, i.p.) transiently reduced heat hyperalgesia in both species. Due to the peptidic nature of DALBK and HOE-140, it is likely that their effects reported herein resulted from blockade of peripheral kinin receptors. Thus, mechanisms operated by kinin B(1) and B(2) receptors, contribute to orofacial heat hyperalgesia induced by CION in both mice and rats. Perhaps kinin B(1) and B(2) receptor antagonists might constitute effective preventive and curative treatments for orofacial thermal hyperalgesia induced by nerve injury.
激肽 B(1)和 B(2)受体偶联的机制与各种神经病变模型相关的感觉变化有关。本研究旨在探讨激肽是否也参与眶下神经缩窄（CION）诱导的口腔面部热痛觉过敏，CION 是一种三叉神经病理性疼痛模型，其对口腔面部感觉刺激表现出持续的超敏反应，在大鼠和小鼠中。雄性瑞士小鼠（30-35g）或 Wistar 大鼠（200-250g；每组 6-10 只）接受 CION 或假手术，并反复接受放置在距触须垫 1cm 处的热源对同侧或对侧鼻尖施加的热（约 50°C）。潜伏期缩短表明出现头部回缩或剧烈的鼻尖抽动，表明存在热痛觉过敏。CION 导致两种物种的长期热痛觉过敏，在手术后第 2 天开始，在小鼠中持续至第 17 天，在大鼠中持续至第 10 天。在手术时将 DALBK 或 HOE-140（分别为肽 B(1)和 B(2)受体拮抗剂，各为 10μl 中的 3nmol）施用于暴露的眶下神经上，可延迟热痛觉过敏的发展。在第 5 天（小鼠）或第 4 天（大鼠）用 Des-Arg(9),Leu(8)-Bradykinin（DALBK，B(1)受体拮抗剂，0.1-1μmol/kg，ip）或 HOE-140（B(2)受体拮抗剂，0.001-1μmol/kg，ip）系统治疗可暂时减轻两种物种的热痛觉过敏。由于 DALBK 和 HOE-140 的肽性质，它们在此报告的作用可能是由于对周围激肽受体的阻断。因此，激肽 B(1)和 B(2)受体介导的机制参与了 CION 在小鼠和大鼠中引起的口腔面部热痛觉过敏。也许激肽 B(1)和 B(2)受体拮抗剂可能构成治疗神经损伤引起的口腔热痛觉过敏的有效预防和治疗方法。
