Oral gabapentin treatment accentuates nerve and peripheral inflammatory responses following experimental nerve constriction in Wistar rats

Abstract

Gabapentin (GBP) is an anti-convulsive drug often used as analgesic to control neuropathic pain. This study aimed at evaluating whether oral GBP treatment could improve nerve inflammation response after sciatic nerve constriction in association with selected pain and motor spontaneous behavior assessments in Wistar rats. We evaluated nerve myeloperoxidase (MPO) and inflammatory cytokines on the 5th day post-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 doses of 30, 60 and 120mg/kg, 60min prior to chronic constriction of the sciatic nerve (CCSN) and during 5 days post-injury, 12/12h. CCSN animals treated with saline were used as controls and for behavioral and inflammation assessments untreated sham-operated rats were also used. On the 5th day, GBP (60 and 120mg/kg) alleviated heat-induced hyperalgesia and significantly increased delta walking scores in CCSN animals, the latter suggesting excitatory effects rather than sedation. GBP (60mg/kg) significantly increased nerve MPO, TNF-α, and IL-1β levels, comparing with the saline group. GBP (120mg/kg) reduced the anti-inflammatory cytokine IL-10 nerve levels compared with the CCSN saline group. Furthermore, GBP (60 and 120mg/kg) increased carrageenan-induced paw edema and peritoneal macrophage migration compared with the CCSN saline group. Altogether our findings suggest that GBP accentuates nerve and peripheral inflammatory response, however confirmed its analgesic effect likely due to an independent CNS-mediated mechanism, and raise some concerns about potential GBP inflammatory side effects in widespread clinical use.

Comparison of the effects of gabapentin and pregabalin on wound healing in rats

“…So it can be deduced that gabapentinoids can interfere at different stages in the inflammatory cascade. In the literature, gabapentin and pregabalin are used for treatment of pain in a wide variety of dose ranges . We studied the effects of 20 mg/kg dose and found that it has a negative effect on wound healing.…”

“…Gabapentin treatment increased peritoneal macrophage migration and carrageenan induced paw oedema, thus suggesting that gabapentin is a proinflammatory factor . The inflammation scores are higher in the gabapentin group in our study also.…”

“…This may be the cause of elongation of inflammatory phase of wound healing and the consequent delay in wound healing process. Camara et al reported that gabapentin accentuates nerve and peripheral inflammatory response, which could be mainly due to an independent central nervous system‐mediated mechanism and raise some concerns about inflammatory side effects when used clinically .…”

BTBR ob/ob mice as a novel diabetic neuropathy model: Neurological characterization and gene expression analyses

“…Emerging evidence strongly supports a role for inflammation in the progression of diabetic retinopathy and nephropathy (28,29), and cross-sectional and prospective studies have demonstrated elevated levels of circulating inflammatory mediators, including cytokines, chemokines, and acute-phase proteins, in the blood of T2D patients (30,31). In a rat nerve injury model, infiltration of inflammatory cells and an increase of cytokines is observed in the SCN (32–34); however, little is known about the role of inflammation in DN in T1D and T2D models. In BTBR ob/ob mice, we observed significant elevation of IL-10, CCL11, CDCL1, and CXCL10 at 13 weeks, as well as an increasing trend for IL-6.…”

Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review

“…84e87 Gabapentinoids reduce inflammatory mediators 69,73,78 and suppress dorsal horn activity 79,83 but contrasting effects have been shown. 84 There is some evidence to support pre-emptive treatment. 72,73,85 Gabapentin was effective in suppressing single motor unit response but not windup, indicating a peripheral mechanism of action.…”