Astroglial involvement in orofacial hyperalgesia in trigeminal nerve-injured rats

Objectives: It has been reported that inferior alveolar nerve (IAN) transection can cause hyperalgesia and/or mechano-allodynia in the whisker pad area innervated by the infraorbital nerve in rats, but the underlying mechanisms are unclear. Since recent neuronal recording studies have suggested that astroglia are involved in exaggerated pain states induced by orofacial inflammation, our aim was to test if brainstem astroglia may be involved in processes contributing to neuropathic facial pain after trigeminal nerve injury. Methods: Recordings of nocifensive behavior and single nociceptive neurons in trigeminal subnucleus caudalis (Vc) were carried out in adult male rats with IAN transection 7 days previously and in sham rats. Intrathecal (i.t.) injections were made of the astroglial inhibitor fluoroacetate (FA) or isotonic saline (as control). Data were compared by one-way ANOVA and Student t-test as appropriate. Results: Heat and mechanical hyperalgesia was significantly depressed after FA administration in IAN-transected rats compared with sham rats (p<0.01). Vc neurons in IAN-transected rats also showed significantly (p< 0.01) greater responses to mechanical and heat stimuli of the whisker pad that were significantly (p<0.01) depressed after i.t. injection of FA but not after saline; neuronal background activity and afterdischarges were not affected by FA administration. Conclusion: These findings suggest that astroglia are involved in the hyperalgesia and Vc nociceptive neuronal hyperexcitability to stimulation of orofacial regions beyond the area innervated by the injured nerve.

Supported by grants from Sato and Uemura Funds and the Dental Research Center, Nihon University School of Dentistry, Nihon University multidisciplinary research grant( KI), CIHR grant MOP-82831 and Japan-Canada Joint Health Research Program grant#07033211-000165.