THE DEVELOPMENT OF TOLERANCE TO INTRATHECAL MORPHINE IN RAT MODELS OFVISCERAL AND CUTANEOUS PAIN

The development of tolerance to intrathecal morphine was studied in ra ts chronically implanted with intrathecal catheters connected to osmot ic minipumps. Measures of cutaneous nociception were the hot plate (HP ) and tail flick (TF) tests. Measures of visceral nociception were vis ceromotor (VM) responses to ramped colorectal distension (CRD) and car diovascular (CV) responses to phasic colorectal distension. Tolerance to a continuous infusion of 6 or 20 nmol/h of morphine sulfate develop ed over 6 days. A significant reduction in the dose-dependent effects of intrathecal morphine in the TF and HP tests and VM and CV responses to CRD occurred in rats receiving continuous infusions of morphine. T he development of tolerance to intrathecal morphine was similar in bot h cutaneous and visceral models. (C) 1998 Elsevier Science Ireland Ltd .