Antiallodynic effect of intrathecal gabapentin and its interaction with clonidine in a pat model of postoperative pain

Background: Systemic administration of gabapentin was shown previously to a ttenuate mechanical allodynia in a rat model of postoperative pain. Because intrathecal administration of gabapentin is effective in other hypersensit ivity states, the authors tested its effect In the postoperative model, its interaction with another antiallodynic agent (clonidine), acid a possible mechanism of gabapentin action (entry into sites of action via an L-amino a cid transporter). Methods: Male Sprague-Dawley rats were anesthetized with halothane, and an incision of the plantaris muscle of right hind paw induced punctate mechani cal allodynia. Withdrawal threshold to von Prey filament application near t he incision site was determined before and 2 h after surgery. Then, an intr athecal injection was performed and thresholds were determined every 30 min for 3 h thereafter. Results: Paw incision induced a mechanical hypersensitivity (mechanical thr eshold > 25 g before incision and < 5 g after). Intrathecal gabapentin dose -dependently (10-100 mu g) reduced mechanical allodynia. Intrathecal inject ion of an inhibitor of L-amino acid transporters or a competitor for this t ransporter, L-leucine, did not reverse the intrathecal effect of gabapentin , The ED50 of intrathecal gabapentin, clonidine, and their combination were 51, 31, and 9 mu g respectively, and isobolographic analysis showed synerg y between gabapentin and clonidine. Conclusions: Intrathecal gabapentin is effective against tactile allodynia that occurs after paw incision, and interacts synergistically with clonidin e. Unlike results in vitro, gabapentin does not obligatorily need to enter cells via the L-amino acid transporter mechanism to achieve its effects in vivo.