The Analgesic Effect of Intrathecal Gabapentin in a Rat Model of Incisional Pain

Park, Soo Seog; Moon, Dong Eon; Kwon, Oh Kyoung; Jang, Yeon; Cho, Eun Chung; Jee, Seung Eun; Song, Ho Kyung; Jeong, Dong Seok

Abstract

BACKGROUND: Gabapentin, an anticonvulsant structurally related to gamma-aminobutyric acid (GABA), was recently reported to be effective in pain associated with reflex sympathetic dystrophy and neuropathy. However, the effects of intrathecal (IT) gabapentin in postoperative pain are unclear. This study was designed to evaluate the analgesic action of IT gabapentin in a rat model of postoperative pain which was similar to human postoperative pain states.
METHODS
Rats were prepared with chronic intrathecal catheter. Under halothane anesthesia, a 1 cm incision was made in the plantar aspect of the hind paw and closed. Rats were divided into 7 groups, a control group (saline 20 microliter intrathecally n = 6); a GP 30 group (gabapentin 30 microgram intrathecally, n = 6); a GP 100 group (gabapentin 100 microgram intrathecally, n = 6); a GP 300 group (gabapentin 300 microgram intrathecally, n = 6); a GP 1000 group (gabapentin 1,000 microgram intrathecally, n = 6); a NS-GP group (saline 10 microliter and gabapentin 300 microgram intrathecally, n = 6) and DS-GP group (D-serine 100 microgram and gabapentin 300 microgram intrathecally, n = 6). The rats were placed on an elevated plastic mesh floor, and withdrawal threshold was determined using calibrated von Frey filaments applied from beneath the test cage to an area adjacent to the wound. A cumulative pain score based on the weight bearing behavior of the rats, and motor deficit score, were also assessed.
RESULTS
In all group, the median withdrawal threshold for punctate hyperalgesia decreased from 148.4 mN before surgery to 1.5 mN-14.5 mN 2 hours after surgery-inducing hyperalgesia and remained unchanged during the 2hr testing period. The IT administration of gabapentin (30 300 microgram) increased the median withdrawal threshold toward preincision values dose-dependently and the nonevoked pain scores were also decreased. But the effects of intrathecal gabapentin were reversed by IT D-serine. The Analgegic effects of gabapentin were observed at doses that had no significant effect on motor function or spontaneous activity.
CONCLUSIONS
These observations suggest that intrathecal gabapentin can modulate the facilitation of spinal nociceptive processing by tissue injury and may offer a therapeutic agent for the treatment of postoperative pain.