title: (-)-Pentazocine induces visceral chemical antinociception, but not thermal, mechanical, or somatic chemical antinociception, in μ-opioid receptor knockout mice.
abstract: BACKGROUND
  (-)-Pentazocine has been hypothesized to induce analgesia via the κ-opioid (KOP) receptor, although the involvement of other opioid receptor subtypes in the effects of pentazocine remains unknown. In this study, we investigated the role of the μ-opioid (MOP) receptor in thermal, mechanical, and chemical antinociception induced by (-)-pentazocine using MOP receptor knockout (MOP-KO) mice.
  
  
  RESULTS
  (-)-Pentazocine-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice. The results obtained from the (-)-pentazocine-induced mechanical and somatic chemical antinociception experiments, which used the hind-paw pressure and formalin tests, were similar to the results obtained from the thermal antinociception experiments in these mice. However, (-)-pentazocine retained its ability to induce significant visceral chemical antinociception, assessed by the writhing test, in homozygous MOP-KO mice, an effect that was completely blocked by pretreatment with nor-binaltorphimine, a KOP receptor antagonist. In vitro binding and cyclic adenosine monophosphate assays showed that (-)-pentazocine possessed higher affinity for KOP and MOP receptors than for δ-opioid receptors.
  
  
  CONCLUSIONS
  The present study demonstrated the abolition of the thermal, mechanical, and somatic chemical antinociceptive effects of (-)-pentazocine and retention of the visceral chemical antinociceptive effects of (-)-pentazocine in MOP-KO mice. These results suggest that the MOP receptor plays a pivotal role in thermal, mechanical, and somatic chemical antinociception induced by (-)-pentazocine, whereas the KOP receptor is involved in visceral chemical antinociception induced by (-)-pentazocine.
authors.affiliation: Research Project for Addictive Substances, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ide
authors.forename: Masabumi
authors.initials: M
authors.lastname: Minami
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.forename: Masamichi
authors.initials: M
authors.lastname: Satoh
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D010146:Pain / Q000188:drug therapy; D010423:Pentazocine / Q000627:therapeutic use*; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: D000700:Analgesics; D017450:Receptors, Opioid, mu; D010423:Pentazocine