Oral gabapentin treatment accentuates nerve and peripheralinflammatory responses following experimentalnerve constriction in Wistar rats

Abstract

Gabapentin (GBP) is an anti-convulsive drug often used as analgesic to control neuropathic pain. Thisstudy aimed at evaluating whether oral GBP treatment could improve nerve inflammation response aftersciatic nerve constriction in association with selected pain and motor spontaneous behavior assessmentsin Wistar rats. We evaluated nerve myeloperoxidase (MPO) and inflammatory cytokines on the 5th daypost-injury, time in which nerve inflammation is ongoing. In addition, the role of GBP on carrageenan-induced paw edema and peritoneal cell migration was analyzed. GBP was given by gavage at dosesof 30, 60 and 120 mg/kg, 60 min prior to chronic constriction of the sciatic nerve (CCSN) and during 5days post-injury, 12/12 h. CCSN animals treated with saline were used as controls and for behavioraland inflammation assessments untreated sham-operated rats were also used. On the 5th day, GBP (60and 120 mg/kg) alleviated heat-induced hyperalgesia and significantly increased delta walking scores inCCSN animals, the latter suggesting excitatory effects rather than sedation. GBP (60 mg/kg) significantlyincreased nerve MPO, TNF- , and IL-1 levels, comparing with the saline group. GBP (120 mg/kg) reducedthe anti-inflammatory cytokine IL-10 nerve levels compared with the CCSN saline group. Furthermore,GBP (60 and 120 mg/kg) increased carrageenan-induced paw edema and peritoneal macrophage migra-tion compared with the CCSN saline group. Altogether our findings suggest that GBP accentuates nerveand peripheral inflammatory response, however confirmed its analgesic effect likely due to an indepen-dent CNS-mediated mechanism, and raise some concerns about potential GBP inflammatory side effectsin widespread clinical use.