Topical Gabapentin Gel Alleviates Allodynia and Hyperalgesia in the Chronic Sciatic Nerve Constriction Injury Neuropathic Pain Model

Background: Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side-effects. Localized therapy may curtail such side-effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain.Methods: Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/ w) was applied three times daily on the ipsilateral or contralateral plantar surface of the hind-paw, whereas in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/ kg) for 30 days. Tests for static-and dynamicmechano- allodynia [paw withdrawal threshold (PWT) to von Frey filament application and latency (PWL) to light brushing], cold-allodynia [paw withdrawal duration (PWD) to acetone], heat-(PWL and PWD) and mechano-hyperalgesia (PWD to pin prick) were utilized to assess pain, whereas effects on locomotion (open field) and motor balance (rotarod and footprint analysis) were measured on days 5-30 post surgery.Results: Topical application of gabapentin gel ipsilaterally but not contralaterally alleviated CCI-induced static-(days 10-30) and dynamicallodynia (days 15-30), suppressed cold-allodynia (days 10-30), heat( days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action. Systemic gabapentin exhibited similar pain profiles but was associated with motor impairment. The gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects.Conclusions: These outcomes disclose an expedient pharmacological validation of the effectiveness of topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the CCIinduced neuropathic pain model. They also advocate further clinical studies on topical gabapentin with regard to certain neuropathic pain syndromes.Significance: Systemic gabapentin neuropathic pain management carries side-effects ostensibly preventable by localized therapy. This study validates the effectiveness potential of a topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the chronic constriction injury-induced neuropathic pain model.