Effects of laparotomy on spontaneous exploratory activity and conditioned operant responding in the rat: a model for postoperative pain.
BACKGROUND
Treatment of postsurgical pain is a major use of analgesics, particularly after abdominal surgery. Analgesics display a number of limiting side effects, including sedation, cognitive impairment, and ileus. Although several postoperative rodent models have been developed, these models do not address these concerns.


METHODS
A model is presented in the rat in which a subcostal incision is performed, penetrating into the peritoneal cavity. The behavioral effects of this surgical procedure are assessed using exploratory locomotor activity and conditioned operant responding. The effects of morphine and ketorolac were assessed in both behavioral paradigms.


RESULTS
Laparotomy decreased ambulation and rearing by approximately 50% 24 h after surgery, and stereotypy (small confined movements) was affected to a lesser degree. The effects of laparotomy on conditioned operant responding were more complex. Total number of sucrose pellets earned was decreased for 2-3 days after laparotomy; however, the amount of time required was increased for up to 2 weeks. Morphine reversed the effects of surgery on ambulation and stereotypy but not rearing, and the dose-effect curve for morphine was shifted to the left by 5 mg/kg ketorolac. Ketorolac produced significant improvement in operant responding after laparotomy, and coadministration of ineffective doses of morphine and ketorolac produced a positive response.


CONCLUSIONS
The current model is consistent with behavioral aspects of postoperative pain seen clinically. The effects of morphine and ketorolac alone and in combination were consistent with the reported analgesic efficacy and occurrence of side effects found with these agents clinically.
Martin
Thomas J
TJ
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA. tjmartin@wfubmc.edu
Buechler
Nancy L
NL
Kahn
William
W
Crews
James C
JC
Eisenach
James C
JC
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003216:Conditioning, Operant / Q000502:physiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000502:physiology*; D020910:Ketorolac / Q000627:therapeutic use; D007813:Laparotomy / Q000523:psychology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010149:Postoperative Pain / Q000523:psychology*; D051381:Rats; D011916:Rats, Inbred F344; D013239:Stereotyped Behavior / Q000187:drug effects; D013395:Sucrose / Q000494:pharmacology
D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013395:Sucrose; D009020:Morphine; D020910:Ketorolac