Enhancement of Caudalis Neuronal Excitability in Trigeminal Nerve-regenerated Rats

Objectives: It is very important to understand the mechanisms underlying the abnormal pain induced by regenerated nerve in order to develop improved treatment approaches in neuropathic pain. However the neuronal mechanism is still remained unclear. Thus, we developed the rat model with inferior alveolar nerve (IAN) transection (IAN rat), and nocifensive behavior and trigeminal spinal subnucleus caudalis (Vc) neuronal activity were precisely analyzed. Methods: IAN was transected and replaced in the alveolar canal in SD rats anesthetized with Na pentobarbital (50 mg/kg, i.p.). Nocifensive behavior to mechanical or heat stimulation of the mental region, neuronal tracing following Fluorogold injection into mental skin and neuronal recording from the Vc were performed in the IAN rats. In addition, phosphorylation of extracellular signal-regulated kinase (pERK) in Vc neurons was analyzed in IAN rats. Results: The escape thresholds to mechanical stimulation of the mental skin were significantly lower at 14 days after IAN transection, whereas head withdrawal latency to heating of the mental skin was significantly longer at 3, 14 and 60 days after that. Mechanical-evoked responses were significantly larger in Vc WDR and LTM neurons 14 days after IAN transection, but not in WDR neurons at 60 days after transection. On the other hand, thermal responses in WDR neurons were significantly lower compared to naïve rats 14 days after transection. The number of pERK-LI cells was significantly larger in IAN rats following mechanical stimulation of the mental skin, but that was significantly smaller after heating of the mental skin. Conclusion: These findings suggest that regenerated IAN may be associated with abnormal neuronal discharge and changes in mechanical and thermal-evoked responses in non-nociceptive as well as nociceptive Vc neurons that may be involved in the development of mechano-allodynia in the area reinnervated by the regenerated IAN.