title: σ1 receptors are involved in the visceral pain induced by intracolonic administration of capsaicin in mice.
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
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pharmacology and Institute of Neuroscience, Faculty of Medicine, University of Granada, Granada, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: González-Cano
authors.forename: Manuel
authors.initials: M
authors.lastname: Merlos
authors.forename: José M
authors.initials: JM
authors.lastname: Baeyens
authors.forename: Cruz M
authors.initials: CM
authors.lastname: Cendán
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage* / Q000633:toxicity*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D010147:Pain Measurement / Q000187:drug effects; D017480:Receptors, sigma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D059265:Visceral Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D017480:Receptors, sigma; D002211:Capsaicin