Abstract | BACKGROUND:
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: 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.
|
Authors | Rafael González-Cano, Manuel Merlos, José M Baeyens, Cruz M Cendán |
Journal | Anesthesiology
(Anesthesiology)
Vol. 118
Issue 3
Pg. 691-700
(Mar 2013)
ISSN: 1528-1175 [Electronic] United States |
PMID | 23299362
(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)
|