TRPV1 expression at a site of lingual nerve injury

Objectives: Nerve injury-induced dysaesthesia is thought to be the result of abnormal discharge from the damaged fibres. The aim of this study was to see if vanilloid receptor 1 (TRPV1), a transducer of noxious stimuli, could be involved in the initiation of this discharge. Methods: In nine anaesthetised adult ferrets the left lingual nerve was sectioned and recovery was permitted for 3 days, 3 weeks or 3 months (3 ferrets per group). After this period, under general anaesthesia (sodium pentobarbitone; induction 42mg/kg i.p., maintenance 3mg/kg i.v.), the animals were perfused with fixative and the left (injured) and right (uninjured) lingual nerves harvested. Frozen longitudinal sections (14μm) were processed using indirect immunofluorescence for TRPV1 and image analysis used to quantify the percentage area of staining (PAS) at the site of injury. Comparisons were made with the results from the uninjured control animals. Results: Three days after injury the PAS of TRPV1 was significantly greater in the injured nerves (15.9±6.6[SD]%) than in either the contralateral (3.9±1.6%) or control (6.9±0.6%) nerves (p<0.05, ANOVA with Tukey-Kramer post hoc test). At 3 weeks the TRPV1 expression was still high in the injured nerves (11.9±5.1%) but by 3 months it had reduced to a similar level to that found in the contralateral nerves (injured: 2.3±0.6%, contralateral nerves: 2.2±1.6%). Conclusion: These data reveal an increase in the expression of TRPV1 in damaged axons 3 days after lingual nerve injury. This coincides with the time of maximum neural discharge and suggests that TRPV1 may be involved in the initiation of the discharge. TRPV1 is therefore a potential therapeutic target for the treatment of neuropathic pain following nerve injury. Supported by the MRC (UK) and GlaxoSmithKline.