Effects of alpha 2-adrenoceptor agonists dexmedetomidine and guanfacine on morphine analgesia and tolerance in rats

Abstract

BackgroundAlpha 2 (α2)-adrenoceptor agonists may be useful for their potential to increase or prolong opioid analgesia while attenuating the development of opioid tolerance. The purpose of this study was to investigate the effects of dexmedetomidine and guanfacine (α2-adrenoceptor agonists) on morphine analgesia and tolerance in rats.MethodsAdult male Wistar albino rats weighing 195–205 g were used. To constitute morphine tolerance, animals received morphine (50 mg/kg) once daily for 3 days. After the last dose of morphine had been injected on day 4, morphine tolerance was evaluated by analgesia tests. The analgesic effects of dexmedetomidine (20 μg/kg), guanfacine (0.5 mg/kg), MK-467 (0.25 mg/kg), and morphine were estimated at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests.ResultsOur findings indicate that dexmedetomidine and guanfacine attenuated the expression of morphine tolerance. In addition, administration of dexmedetomidine with morphine increased morphine analgesia. On the contrary, data suggested that MK-467 (an α2-adrenoceptor antagonist) decreased morphine analgesia and increased morphine tolerance in analgesia tests.ConclusionIn conclusion, we observed that co-injection of dexmedetomidine or guanfacine with morphine attenuated the expression of tolerance to the analgesic effect of morphine and that dexmedetomidine enhanced the morphine analgesia.

Successful Treatment of Refractory Cancer Pain and Depression with Continuous Intrathecal Administration of Dexmedetomidine and Morphine: A Case Report

“…DEX, when it was given intrathecally, enhanced the analgesic effects of morphine and reduced the dosage of morphine required. This result is highly consistent with previous studies, showing that DEX leads to a reduction in the expression of morphine analgesic tolerance and enhances its analgesic effects [19].…”

<p>Upregulation of μ-Opioid Receptor in the Rat Spinal Cord Contributes to the α2-Adrenoceptor Agonist Dexmedetomidine-Induced Attenuation of Chronic Morphine Tolerance in Cancer Pain</p>

“…21 The role of α2-AR agonists in the development of morphine tolerance has been studied in several researches. Based on a normal rat or non-cancer pain rat model, 17 coadministration of DEX has been shown to inhibit the development of chronic analgesic tolerance to morphine. Whereas the underlying molecular mechanism still remains unclear, and the effect of α2-AR agonist DEX on morphine tolerance in cancer pain has not been reported.…”

The Inflammatory Nature of Post-surgical Delirium Predicts Benefit of Agents With Anti-TNF Effects, Such as Dexmedetomidine

“…Similarly, anxiety states in patients exhibit high proinflammatory cytokine activity (Hou et al, 2017 ), and dexmedetomidine has anxiolytic properties in rats (Ji et al, 2014 ). Likewise, both dexmedetomidine (Gursoy et al, 2011 ) and anti-TNF agents (Shen et al, 2011 ; Sun et al, 2012 ) attenuate the expression of the tolerance to morphine that develops with its continued use in chronic pain.…”