Medullary neural circuit regeneration after trigeminal nerve transection

The inferior alveolar nerve (IAN) comprises several types of sensory fibers. To clarify whether each type of primary afferent is regenerated comparably after injury, we developed a model of complete IAN transection (IANX) in mice. A retrograde tracer, fluoro-gold, injected into the mental skin was transferred to the cell bodies of a subset of isolectin B4 (IB4)-binding (non-peptidergic C) or CGRP-positive (peptidergic C) neurons at 2 weeks post-axotomy, indicating that the injured C afferents had regenerated anatomically. IANX led to a decrease of IB4-binding and CGRP immunoreactivity (IR) in the trigeminal ganglion (TG) and within the trigeminal spinal subnucleus caudalis (Vc) (i.e. terminals of the central branch of TG neurons). Two weeks after IANX, the reduction in IB4-binding activity and CGRP expression in the TG recovered to the control level; however, IB4-binding within the Vc did not, suggesting that central branch non-peptidergic neurons remained impaired. Two weeks after IANX, pinching or heat stimulus-induced extracellular signal-regulated kinase phosphorylation (pERK) was restored to the control level, but in the case of pinch stimulation the distribution pattern of pERK-IR cells was altered in the Vc. Taken together, our results support the possibility that peptidergic neurons regenerate more efficiently than non-peptidergic neurons after trigeminal nerve injury.