Abstract
Opioid analgesics are effective in the treatment of chronic pain, but they have serious adverse effects such as development of tolerance and dependence. Adrenergic α(2) agonists and μ-opioid receptor agonists show synergistic potentiation and cross-tolerance in spinal analgesia, whereas α(2)-adrenergic antagonists have shown pronociceptive effects. However, at ultralow doses, spinal α(2)-adrenergic antagonists have been reported to paradoxically enhance opioid antinociception. New data have suggested a functional μ-opioid-α(2)-adrenoceptor complex, which may help in interpreting the paradoxical effect of the α(2)-adrenergic antagonists. In the present study we assessed the effects of low doses of atipamezole, a nonselective α(2)-adrenergic antagonist, on both systemic and spinal morphine antinociception and tolerance. Antinociception was assessed in male Sprague-Dawley rats using hotplate, tail-flick, and paw pressure tests. Spinal or systemic opioid tolerance was induced for 4 days. The effects of both intrathecal and subcutaneous atipamezole on acute morphine-induced antinociception and established morphine tolerance were studied. Systemic or spinal atipamezole itself did not produce antinociception at the doses studied (subc...Continue Reading
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