title: Dissociation between post-surgical pain behaviors and spinal Fos-like immunoreactivity in the rat.
abstract: Previous studies have demonstrated that Fos-like immunoreactivity is increased in spinal dorsal horn neurons in several pain models, and have suggested that Fos-like immunoreactivity could be used as a marker of neurons activated by painful stimulation. In the present study, we evaluated nociceptive behaviors and spinal Fos-like immunoreactivity in a rat skin incision model of post-operative pain. In this model, evoked and non-evoked pain behaviors were observed at least for 2 days after paw surgery, an increased number of Fos-like immunoreactive neurons was observed in the spinal dorsal horn at lumbar levels 4-5 two-hour post-surgery. The number of Fos-like immunoreactive neurons was significantly greater in animals with skin-muscle incision compared to animals with skin-alone incision. Interestingly, spinal Fos-like immunoreactivity was quickly normalized in rats with paw surgery at later time points (8 and 24 h post-surgery), whereas nociceptive behaviors were still observed. Furthermore, at 24 h post-surgery, spinal Fos-like immunoreactivity induced by thermal stimulation (42, 44, 46, 48, 52 degrees C for 15 s) was not significantly different between sham animals and animals with surgery. In both groups, an increase in spinal Fos-like immunoreactive neurons was observed with increasing temperatures, with similar laminar distribution. Finally, systemic morphine reduced post-operative pain and Fos-like immunoreactivity in a naloxone reversible manner, with greater potency and efficacy on behavioral endpoints than on Fos-like immunoreactivity. These results demonstrate a different profile of nociceptive behaviors and spinal Fos-like immunoreactivity in the rat skin incision model, suggesting a limited potential of spinal Fos-like immunoreactivity to study post-surgical pain and its pharmacology.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA. Chang.Z.Zhu@abbott.com
authors.forename: Chang Z
authors.initials: CZ
authors.lastname: Zhu
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Nikkel
authors.forename: Brenda
authors.initials: B
authors.lastname: Martino
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bitner
authors.forename: Michael W
authors.initials: MW
authors.lastname: Decker
authors.forename: Prisca
authors.initials: P
authors.lastname: Honore
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D062109:Dermatologic Surgical Procedures; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000601:surgery; D007150:Immunohistochemistry; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009132:Muscles / Q000601:surgery; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010149:Postoperative Pain / Q000503:physiopathology* / Q000517:prevention & control; D020671:Posterior Horn Cells / Q000737:chemistry* / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000737:chemistry* / Q000187:drug effects; D013696:Temperature; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D009270:Naloxone; D009020:Morphine