Department of Pharmacology and Institute of Neuroscience, Faculty of Medicine, University of Granada, Granada, Spain.
Anesthesiology. 2013 Mar;118(3):691-700. doi: 10.1097/ALN.0b013e318280a60a.
Visceral pain is an important and prevalent clinical condition whose treatment is challenging. Sigma-1 (σ1) receptors modulate somatic pain, but their involvement in pure visceral pain is unexplored.
The authors evaluated the role of σ1 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 σ1 receptor knockout (σ1-KO) (n = 10 per group) mice, selective σ1 receptor antagonists (BD-1063, S1RA, and NE-100), and control drugs (morphine and ketoprofen).
The intracolonic administration of capsaicin (0.01-1%) induced concentration-dependent visceral pain-related behaviors and referred hyperalgesia in both WT and σ1-KO mice. However, the maximum number of pain-related behaviors induced by 1% capsaicin in σ1-KO mice (mean ± SEM, 22 ± 2.9) was 48% of that observed in WT animals (46 ± 4.2). Subcutaneous administration of the σ1 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 σ1-KO mice. Thus, the effects of these drugs are specifically mediated by σ1 receptors. Morphine produced an inhibition of capsaicin-induced visceral pain in WT and σ1-KO mice, whereas ketoprofen had no effect in either mouse type.
These results suggest that σ1 receptors play a role in the mechanisms underlying capsaicin-induced visceral pain and raise novel perspectives for their potential therapeutic value.
内脏痛是一种重要且普遍的临床病症，其治疗具有挑战性。σ1（σ1）受体调节躯体疼痛，但它们在纯内脏疼痛中的作用尚未得到探索。
作者使用野生型（WT）（每组 12 只）和 σ1 受体敲除（σ1-KO）（每组 10 只）小鼠、选择性 σ1 受体拮抗剂（BD-1063、S1RA 和 NE-100）和对照药物（吗啡和酮洛芬），评估 σ1 受体在结肠内辣椒素诱导的内脏痛（与疼痛相关的行为和向腹壁的机械性痛觉过敏）中的作用。
结肠内给予辣椒素（0.01-1%）在 WT 和 σ1-KO 小鼠中均引起浓度依赖性内脏痛相关行为和向腹壁的痛觉过敏。然而，1%辣椒素引起的 σ1-KO 小鼠最大疼痛相关行为数（平均值±SEM，22±2.9）为 WT 动物观察到的 48%（46±4.2）。皮下给予 σ1 受体拮抗剂 BD-1063（16-64mg/kg）、S1RA（32-128mg/kg）和 NE-100（8-64mg/kg）剂量依赖性地减少行为反应的数量（分别减少 53%、62%和 58%）并将向机械对照阈值的痛觉过敏逆转（0.53±0.05g）在 WT 小鼠中。相比之下，这些药物在 σ1-KO 小鼠中没有产生变化。因此，这些药物的作用是由 σ1 受体特异性介导的。吗啡对 WT 和 σ1-KO 小鼠的辣椒素诱导内脏痛均有抑制作用，而酮洛芬在两种小鼠类型中均无作用。
这些结果表明 σ1 受体在辣椒素诱导的内脏痛的机制中起作用，并为其潜在的治疗价值提供了新的视角。
