• L R Poree, T Z Guo, W S Kingery, and M Maze.
• Department of Anesthesia, Stanford University, California, USA. poree@leland.stanford.edu
• Anesth. Analg. 1998 Oct 1; 87 (4): 941-8.

UnlabelledThis study investigated the analgesic potency and site of action of systemic dexmedetomidine, a selective alpha2-adrenoceptor (alpha2AR) agonist, in normal and neuropathic rats. Ligation of the L5-6 spinal nerves produced a chronic mechanical and thermal neuropathic hyperalgesia in rats. von Frey fibers and a thermoelectric Peltier device were used to measure mechanical and heat withdrawal thresholds over the hindpaw. Systemic dexmedetomidine dose-dependently increased the mechanical and thermal thresholds in the control animals (50% effective dose [ED50] 144 and 180 microg/kg intraperitoneally [i.p.], respectively). Neuropathic animals responded to much smaller doses of dexmedetomidine with mechanical and thermal ED50 values of 52 and 29 microg/kg i.p., respectively. There was no difference between the control and neuropathic animals with respect to dexmedetomidine-evoked sedation, as determined by decreased grid crossings in an open-field activity chamber (ED50 12 and 9 microg/kg i.p., respectively). Atipamezole, a selective alpha2AR antagonist, blocked the analgesic and sedative actions of dexmedetomidine inboth the neuropathic and control animals. However, L-659,066, a peripherally restricted alpha2AR antagonist, could only block the analgesic actions of dexmedetomidine in the neuropathic rats, with no effect in control animals. In conclusion, nerve injury enhanced the analgesic but not the sedative potency of systemic dexmedetomidine and may have shifted the site of alpha2 analgesic action to outside the blood-brain barrier.ImplicationsWe tested the analgesic efficacy of the alpha2 agonist dexmedetomidine in normal and nerve-injured rats. The analgesic potency of dexmedetomidine was enhanced after nerve injury with a site of action outside the central nervous system. Peripherally restricted alpha2 agonists may be useful in the management of neuropathic pain.

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