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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.
AuthorsChang Z Zhu, Arthur L Nikkel, Brenda Martino, Robert S Bitner, Michael W Decker, Prisca Honore
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 531 Issue 1-3 Pg. 108-17 (Feb 15 2006) ISSN: 0014-2999 [Print] Netherlands
PMID16438960 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Analgesics, Opioid
  • Narcotic Antagonists
  • Proto-Oncogene Proteins c-fos
  • Naloxone
  • Morphine
Topics
  • Analgesics, Opioid (pharmacology)
  • Animals
  • Dermatologic Surgical Procedures
  • Dose-Response Relationship, Drug
  • Hindlimb (surgery)
  • Immunohistochemistry
  • Male
  • Morphine (pharmacology)
  • Muscles (surgery)
  • Naloxone (pharmacology)
  • Narcotic Antagonists (pharmacology)
  • Pain, Postoperative (physiopathology, prevention & control)
  • Posterior Horn Cells (chemistry, drug effects)
  • Proto-Oncogene Proteins c-fos (analysis)
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord (chemistry, drug effects)
  • Temperature
  • Time Factors

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