ABSTRACT
Purpose: Remifentanil is one of the most commonly used opioids intraoperatively. Previous reports indicate that long-term use of opioids may lead to cross-tolerance to remifentanil, which poses a challenge in the control of acute pain intraoperatively. However, there is limited information regarding cross-tolerance to remifentanil, especially in visceral pain. Therefore, this study aimed to examine cross-tolerance to remifentanil in somatic and visceral tolerance using morphine-tolerant rats. Methods: Six male Sprague-Dawley rats were allocated to the morphine and saline groups each. Tolerance to the antinociceptive effect of morphine was induced in rats in the morphine group. Remifentanil was continuously infused intravenously at 10 mcg/kg/min for 120 min to assess cross-tolerance from morphine to remifentanil. The antinociceptive effects on somatic and visceral nociceptive stimuli were measured using the tail-flick (TF) and colorectal distension (CD) tests, respectively. The antinociceptive efficacy was evaluated by converting the response threshold to the percentage maximal possible effect (%MPE). Results: Remifentanil increased the %MPE in the morphine and saline groups in both the tests; however, the increase in %MPE was attenuated significantly in the morphine group compared with that in the saline group at 60, 90, and 120 min (all P < 0.01) in the TF test and at 90 and 120 min in the CD test (all P <0.05). Conclusion: Our results indicate that morphine-tolerant rats exhibit cross-tolerance to remifentanil's acute antinociceptive effects on somatic and visceral stimuli. Cross-tolerance to remifentanil should be considered in the perioperative management of patients using morphine.
ABSTRACT
PURPOSE: Transient receptor potential vanilloid 1 (TRPV1) not only is activated by multiple stimuli but also is involved with histamine-induced itch. The effects of TRPV1 on morphine-induced itch are unknown. We examined the effects of intrathecal administration of TRPV1 antagonist on morphine-induced itch, body temperature, and antinociception for mice. METHODS: Each C57/BL6j mouse was intrathecally administered with one of the following solutions: morphine, SB366791 (as the TRPV1 antagonist), morphine + SB366791, saline, or vehicle. For each mouse, each instance of observed scratching behavior was counted, the body temperature was measured, and the nociceptive threshold was determined using the tail-immersion test. RESULTS: SB366791 dose-dependently reduced the scratching behavior induced by the administration of morphine. SB366791 and the morphine + SB366791 groups did not manifest an increase in body temperature. Antinociceptive effects were observed to occur dose-dependently for morphine but not for SB366791. Compared with morphine alone, the administration of morphine + SB366791 did not reduce significant antinociceptive effects. CONCLUSION: We propose that an intrathecal TRPV1 antagonist, SB366791, reduced morphine-induced itch without causing hyperthermia and did not suppress morphine-induced antinociception for mice.
