Chronic intrathecal infusion of gabapentin prevents nerve ligation-induced pain in rats

Background. Gabapentin is an anticonvulsant and adjuvant analgesic. It is effective in several pain studies. Neuropathic pain is the most difficult type of pain to treat. In this study, we examined if intrathecal gabapentin could prevent nerve injury-induced pain. Methods. Under isoflurane anaesthesia, male Sprague-Dawley rats (200-250 g) underwent right L5/6 spinal nerve ligation and placement of an intrathecal catheter connected to an infusion pump. After surgery, intrathecal saline or gabapentin (20 mu g h(-1)) was given for 7 days (n = 8 per group). The right hind paw withdrawal threshold to von Frey filament stimuli and withdrawal latency to radiant heat were determined before (baseline) and once daily for 7 days after surgery. Haematoxylin and eosin and toluidine blue staining were used to evaluate the neurotoxicity of gabapentin (40 mu g h(-1)). Results. Seven days after nerve ligation, the affected paw withdrawal threshold and latency of saline-treated rats decreased from the baseline 11.7 (11.7-22.2) [median (inter-quartile range)] to 1.6 (0.9-3.2) g and 10.8 (10.5-11.2) to 4.3 (4.2-7) s, respectively. Rats receiving gabapentin (20 mu g h(-1)) had higher withdrawal threshold [9.9 (9.9-19.3) g] and latency [11.5 (9.7-11.9) s] on day 7 after ligation. No obvious histopathological change or growth retardation was detected after intrathecal gabapentin (40 mu g h(-1)) infusion. Conclusions. We showed a preventative effect of intrathecal gabapentin on the development of nerve injury-induced mechanical allodynia and thermal hyperalgesia. Our data suggest that continuous intrathecal gabapentin may be considered as an alternative for the prevention of nerve injury-induced pain.