σ1 Receptors Are Involved in the Visceral Pain Induced by Intracolonic Administration of Capsaicin in Mice
σ1 Receptors Are Involved in the Visceral Pain Induced by Intracolonic Administration of Capsaicin in Mice
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DOI：
10.1097/aln.0b013e318280a60a
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发表时间：
2013-03-01
期刊：
影响因子：
8.8
通讯作者：
Cendan, Cruz M.
中科院分区：
文献类型：
--
作者：
Gonzalez-Cano, Rafael;Merlos, Manuel;Cendan, Cruz M.
背景：内脏疼痛是一种重要且普遍的临床疾病，其治疗具有挑战性。Sigma-1（sigma（1））受体调节躯体疼痛，但它们参与纯粹内脏疼痛的研究尚未展开。作者评价了sigma（1）受体在结肠内辣椒素诱导的内脏痛中的作用（疼痛相关行为和腹壁的机械性痛觉过敏）（每组n = 12）和sigma（1）受体敲除（sigma（1）-KO）（每组n = 10）小鼠，选择性sigma（1）受体拮抗剂（BD-1063、S1 RA和NE-100）和对照药物（吗啡和酮洛芬）。辣椒素的结肠内给药（0.01-1%）在WT和sigma（1）-KO小鼠中诱导浓度依赖性内脏疼痛相关行为和牵涉性痛觉过敏。然而，在sigma（1）-KO小鼠中由1%辣椒素诱导的疼痛相关行为的最大数量（平均值+/- SEM，22 +/- 2.9）是在WT动物中观察到的疼痛相关行为的48%（46 +/- 4.2）。皮下施用σ（1）受体拮抗剂BD-1063（16-64 mg/kg），S1RA（32-128 mg/kg）和NE-100（8-64 mg/kg）剂量依赖性地减少行为反应的次数（分别为53、62和58%），并在WT小鼠中将牵涉痛觉过敏逆转至机械控制阈值（0.53 +/- 0.05 g）。相反，这些药物在sigma（1）-KO小鼠中没有产生变化。因此，这些药物的作用是由sigma（1）受体特异性介导的。吗啡产生抑制辣椒素诱导的内脏痛在WT和sigma（1）-KO小鼠，而酮洛芬在任何小鼠type.Conclusion没有效果：这些结果表明，sigma（1）受体发挥作用的机制辣椒素诱导的内脏痛，并提高其潜在的治疗价值的新观点。
Background: Visceral pain is an important and prevalent clinical condition whose treatment is challenging. Sigma-1 (sigma(1)) receptors modulate somatic pain, but their involvement in pure visceral pain is unexplored.Methods: The authors evaluated the role of sigma(1) receptors in intracolonic capsaicin-induced visceral pain (pain-related behaviors and referred mechanical hyperalgesia to the abdominal wall) using wild-type (WT) (n = 12 per group) and sigma(1) receptor knockout (sigma(1)-KO) (n = 10 per group) mice, selective sigma(1) receptor antagonists (BD-1063, S1RA, and NE-100), and control drugs (morphine and ketoprofen).Results: The intracolonic administration of capsaicin (0.01-1%) induced concentration-dependent visceral pain-related behaviors and referred hyperalgesia in both WT and sigma(1)-KO mice. However, the maximum number of pain-related behaviors induced by 1% capsaicin in sigma(1)-KO mice (mean +/- SEM, 22 +/- 2.9) was 48% of that observed in WT animals (46 +/- 4.2). Subcutaneous administration of the sigma(1) receptor antagonists BD-1063 (16-64 mg/kg), S1RA (32-128 mg/kg), and NE-100 (8-64 mg/kg) dose-dependently reduced the number of behavioral responses (by 53, 62, and 58%, respectively) and reversed the referred hyperalgesia to mechanical control threshold (0.53 +/- 0.05 g) in WT mice. In contrast, these drugs produced no change in sigma(1)-KO mice. Thus, the effects of these drugs are specifically mediated by sigma(1) receptors. Morphine produced an inhibition of capsaicin-induced visceral pain in WT and sigma(1)-KO mice, whereas ketoprofen had no effect in either mouse type.Conclusion: These results suggest that sigma(1) receptors play a role in the mechanisms underlying capsaicin-induced visceral pain and raise novel perspectives for their potential therapeutic value.