Differential effects of intrathecally administered morphine and its interaction with cholecystokinin-B antagonist on thermal hyperalgesia following two models of experimental mononeuropathy in the rat.
BACKGROUND
Cholecystokinin-B receptor activation has been reported to reduce morphine analgesia. Neuropathic pain is thought to be relatively refractory to opioids. One possible mechanisms for a reduced effect of morphine on neuropathic pain is the induction of cholecystokinin in the spinal cord by nerve injury. The authors evaluated the role of the spinal cholecystokinin-B receptor on morphine analgesia in two rat neuropathic pain models: chronic constriction injury and partial sciatic nerve injury.


METHODS
A chronic constriction injury is created by placing four loosely tied ligatures around the right sciatic nerve. A partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. All drugs were injected intrathecally 7 and 11 days after the nerve injury. The effect of the drugs was reflected in the degree of paw withdrawal latency to thermal nociceptive stimulation. The paw withdrawal latencies of injured and uninjured paws were measured 5, 15, 30, and 60 min after the drugs were injected.


RESULTS
In the chronic constriction injury model, intrathecal morphine increased the paw withdrawal latencies of injured and uninjured paws. PD135158, a cholecystokinin-B receptor antagonist, potentiated the analgesic effect of morphine on injured and uninjured paws. In the partial sciatic nerve injury model, the effect of morphine on the injured paw was less potent than that on the uninjured paw, and PD135158 potentiated the morphine analgesia in the uninjured paw and had only a minor effect on the morphine analgesia in the injured paw.


CONCLUSIONS
The effectiveness of morphine for thermal hyperalgesia after nerve injury depends on the type of nerve injury. The role of the cholecystokinin-B receptor in morphine analgesia in thermal hyperalgesia after nerve injury also depends on the type of nerve injury.
D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D004357:Drug Synergism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D012584:Sciatic Nerve / Q000293:injuries