Topical gabapentin gel alleviates allodynia and hyperalgesia in the chronic sciatic nerve constriction injury neuropathic pain model

摘要

Background: Systemic gabapentin is a mainstay treatment for neuropathic pain though there areudside effects. Localized therapy may curtail such side effects so a topical gabapentin dermaludapplication was examined in the chronic constriction injury (CCI) model of neuropathic pain.udMethods: Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gelud(10% w/w) was applied three-times daily on the ipsilateral or contralateral plantar surface of theudhind-paw while in a concurrent systemic study, gabapentin was intraperitoneally administereduddaily (75 mg/kg) for 30 days. Tests for static- and dynamic- mechano-allodynia (paw withdrawaludthreshold [PWT] to von-Frey filament application and latency [PWL] to light brushing), coldallodyniaud(paw withdrawal duration [PWD] to acetone), heat- (PWL and PWD) and mechanohyperalgesiaud(PWD to pin-prick) were utilized to assess pain while effects on locomotion (openudfield) and motor balance (rotarod and footprint-analysis) were measured on days 5-30 postsurgery.udResults: Topical application of gabapentin gel ipsilaterally but not contralaterally alleviatedudCCI-induced static- (days 10-30) and dynamic-allodynia (days 15-30), suppressed cold-allodyniaud(days 10-30), heat- (days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action.udSystemic gabapentin exhibited similar pain profiles but was associated with motor impairment.udThe gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid ofudunwanted systemic side-effects.udConclusions: These outcomes disclose an expedient pharmacological validation of theudeffectiveness of topical gabapentin gel against an extensive range of nociceptive stimulusudmodalities utilizing the CCI-induced neuropathic pain model. They also advocate further clinicaludstudies on topical gabapentin with regard to certain neuropathic pain syndromes.