The synergistic antinociceptive interactions of morphine and dexmedetomidine in rats with nerve-ligation injury.

BACKGROUND Peripheral nerve injury may result in chronic neuropathic pain, which is characterized by spontaneous pain, hyperalgesia, and allodynia. Intrathecal administration of opioids and α2-adrenoceptor agonists produces spinal analgesia by activation of opioidergic and noradrenergic systems. In our study, we have compared the synergistic antiallodynic interaction and side-effects of intrathecal morphine and dexmedetomidine in a rat model of neuropathic pain. METHODS Male Wistar rats, weighing 380-440 g, were treated with tight ligation of left L5-6 spinal nerves and a chronic catheter was implanted intrathecally. Morphine and dexmedetomidine were administered intrathecally to obtain the dose-response curves and the 50 % effective doses (ED50) for each drug and fractional analysis of the ED50 of each drug administered concurrently was performed to examine the interaction. Mechanical allodynia was measured by using application of von Frey filaments to the hindpaw. RESULTS Intrathecal administration of morphine and dexmedetomidine alone and in combination resulted in a dose-dependent antiallodynic effect, and the combination produced a synergistic effect-state magnitude. Moreover, the incidence of side-effects was higher when morphine or dexmedetomidine were administered in high doses alone and extremely low when these two drugs were used in combination. These results are suggestive of a synergistic effect at lower doses of both drugs. CONCLUSIONS These findings may provide a rationale for combining such drugs for the improvement of human postoperative or neuropathic pain treatment in the future.