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σ1 receptors are involved in the visceral pain induced by intracolonic administration of capsaicin in mice.

AbstractBACKGROUND:
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.
METHODS:
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).
RESULTS:
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.
CONCLUSION:
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.
AuthorsRafael González-Cano, Manuel Merlos, José M Baeyens, Cruz M Cendán
JournalAnesthesiology (Anesthesiology) Vol. 118 Issue 3 Pg. 691-700 (Mar 2013) ISSN: 1528-1175 [Electronic] United States
PMID23299362 (Publication Type: Journal Article)
Chemical References
  • Receptors, sigma
  • Capsaicin
Topics
  • Animals
  • Capsaicin (administration & dosage, toxicity)
  • Colon (drug effects, metabolism)
  • Female
  • Mice
  • Mice, Knockout
  • Pain Measurement (drug effects)
  • Receptors, sigma (deficiency, genetics, physiology)
  • Visceral Pain (chemically induced, metabolism, physiopathology)

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