title: Role of micro-opioid receptors in formalin-induced pain behavior in mice.
abstract: Intraplantar formalin injection is widely used as an experimental model of tonic pain. We investigated the role of endogenous micro-opioid receptor mechanisms in formalin-induced nocifensive behavior in mice. The flinching response induced by formalin (2%, 20 microl) was studied in mice with normal (wild type, n = 8) and absent (homozygous micro-opioid receptor knockout, n = 8) micro-opioid receptor levels. The flinch responses were counted every 5 min for 60 min post-formalin injection. Lumbar spinal cord (L4, 5) was harvested 2 h post-formalin injection to examine c-Fos expression using immunohistochemistry. The effects of naloxone (5 mg/kg, sc) administered 30 min before the intraplantar formalin injection on the flinching response of wild-type mice (n = 7) were also recorded. The second-phase formalin response (10-60 min after formalin) was higher in homozygous micro-opioid receptor knockout mice compared to the wild-type mice (P < 0.01). Naloxone administration in wild-type mice before formalin injection resulted in pain behavior similar to that observed in homozygous micro-opioid receptor knockout mice (P > 0.05). The c-Fos expression induced by formalin injection in the knockout mice was not different from that observed in wild-type mice. Our results suggest that the endogenous micro-opioid system is activated by intraplantar formalin injection and exerts a tonic inhibitory effect on the pain behavior. These results suggest an important modulatory role of endogenous micro-opioid receptor mechanisms in tonic pain states.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Cheng-Shui
authors.initials: CS
authors.lastname: Zhao
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Tao
authors.forename: Jill M
authors.initials: JM
authors.lastname: Tall
authors.forename: David M
authors.initials: DM
authors.lastname: Donovan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Meyer
authors.forename: Srinivasa N
authors.initials: SN
authors.lastname: Raja
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D005557:Formaldehyde / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D017450:Receptors, Opioid, mu / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D017450:Receptors, Opioid, mu; D005557:Formaldehyde; D009270:Naloxone