Search

BackgroundPrevious evidence suggests that opioid-tolerant patients are less responsive to local anesthetics (LAs) for postoperative pain management.MethodsTo determine whether this apparent loss of LA potency is due to an intrinsic change in the peripheral nerve, the effect of systemic morphine was assessed on the potency of lidocaine-induced block of the compound action potential in isolated rat sciatic nerves. Analgesic efficacy was assessed with the heat withdrawal assay.ResultsWhile acute administration of 10 mg/kg morphine had no detectable influence on lidocaine potency, seven daily subcutaneous injections of morphine produced a three-fold decrease in potency (EC50 for block A and C waves for naive rats were [mean ± SD] 186 ± 32 μM [n = 6] and 201 ± 31 μM [n = 6], respectively, vs. 608 ± 53 μM [n = 6] and 613 ± 42 μM [n = 6], respectively [P < 0.001], in nerves from rats that had received seven daily injections of morphine [10 mg/kg]). This loss in potency was both dose-dependent and injection number dependent, such that the magnitude of the loss of lidocaine potency was significantly (n = 6; P < 0.01) correlated (r2 = 0.93) with the development of morphine tolerance. Interestingly, despite the complete recovery of analgesic efficacy within days after cessation of morphine administration, the morphine-induced decrease in lidocaine potency was fully manifest even 35 days after the last morphine injection. Coadministration of naloxone (1 mg/kg, intraperitoneally), but not of naloxone methiodide (1 mg/kg, subcutaneously), with each of seven daily injections of morphine blocked the decrease in lidocaine potency.ConclusionsThese preclinical data suggest that the morphine-induced decrease in LA potency is due, at least in part, to the intrinsic changes in the peripheral nerve. Identification of the underlying mechanisms may suggest strategies for more effective postoperative pain management in the growing population of opioid-tolerant patients.

Background Experimental data suggest general anesthetics preferring γ-aminobutyric acid receptor type A may increase postoperative pain in patients with persistent inflammation. The current study was designed to begin to test this hypothesis. Methods Groups of rats were defined by the presence of inflammation, surgical intervention, and/or the type of general anesthetic used for a 3-h period of anesthesia. Persistent inflammation was induced with complete Freund adjuvant. The surgical intervention was a plantar incision. Three mechanistically distinct general anesthetics were used: pentobarbital, ketamine/xylazine, and isoflurane. Ongoing pain and hypersensitivity were assessed with guarding behavior analysis and the von Frey test, respectively. Results There was no influence of general anesthetic type on the magnitude or time course of recovery from postoperative hypersensitivity in the absence of persistent inflammation. However, in the presence of persistent inflammation, recovery from hypersensitivity was significantly slower in the pentobarbital group than in the ketamine/xylazine or isoflurane groups. The pentobarbital effect was significant within 3 days of surgery and persisted through the remainder of the testing period. A comparable delay in recovery was observed in pentobarbital-anesthetized inflamed rats not subjected to hind paw incision. The time to 50% recovery in the pentobarbital-treated inflamed groups was almost double that in the other groups. No differences were observed between ketamine/xylazine and isoflurane. Pentobarbital exposure did not increase guarding scores. Conclusions These results suggest that general anesthetics preferring γ-aminobutyric acid receptor type A may have deleterious consequences when used in the presence of persistent inflammation.