Visceral analgesic tolerance to intrathecal butorphanol in rats.
OBJECTIVE
Recent experimental data suggest that intrathecal (it) kappa-opioid agonists produce profound visceral analgesia. This study investigated the development of visceral analgesic tolerance to it butorphanol, a potent kappa-agonist that has fewer side effects than commonly used it opioids. Understanding of this tolerance could make it butorphanol more effective in treating chronic visceral pain.


METHODS
This was a randomized, controlled animal study involving 80 Sprague-Dawley rats. Rats implanted with lumbar it catheters were infused either with it saline or butorphanol (52 nmol.hr-1) for 96 hr. Six hours afterwards, each rat was challenged once with one of the differing it butorphanol doses to construct dose-response curves. Visceral analgesia was evaluated by the abdominal writhing responses to the acetic acid injected intraperitoneally. The time of the first writhe and the total number of writhes were recorded.


RESULTS
For both the saline- and butorphanol-infused groups, a higher challenge dose of it butorphanol produced longer time for the first writhe to occur (P < 0.01, one-way ANOVA), and fewer writhes occurring within 30 min (P < 0.01, one-way ANOVA). However, the dose response curves of the butorphanol-infused groups were shifted rightward (P < 0.001, partial F test).


CONCLUSIONS
The challenge doses of it butorphanol produced dose-dependent visceral analgesia in both the saline- and butorphanol-infused groups, confirming its efficacy. The butorphanol-infused groups showed dose-response shifts, demonstrating the development of tolerance to this visceral analgesia.
Tsang
B K
BK
Department of Anesthesiology, University of Mississippi Medical Center, Jackson 39216, USA. bktsang@anesthesia.umsmed.edu
He
Z
Z
Wongchanapai
W
W
Ho
I K
IK
Eichhorn
J H
JH
D019342:Acetic Acid / Q000008:administration & dosage / Q000009:adverse effects; D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D002077:Butorphanol / Q000008:administration & dosage*; D002408:Catheters, Indwelling; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D015918:Infusion Pumps, Implantable; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D007509:Irritants / Q000008:administration & dosage / Q000009:adverse effects; D008159:Lumbar Vertebrae; D008297:Male; D009294:Narcotics / Q000819:agonists; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010537:Peritoneum / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D013997:Time Factors
D000701:Analgesics, Opioid; D007509:Irritants; D009294:Narcotics; D017473:Receptors, Opioid, kappa; D019342:Acetic Acid; D002077:Butorphanol