Changes in expression of growth-associated protein-43 in trigeminal ganglion neurons and of the jaw opening reflex following inferior alveolar nerve transection in rats.

The aim of the present study was to clarify an involvement of growth-associated protein-43 (GAP-43) in the regeneration of primary afferent trigeminal ganglion (TG) neurons following inferior alveolar nerve transection (IANX). A larger number of GAP-43 immunoreactive (GAP-43 IR) TG neurons was observed in rats 3 d after IANX compared with sham rats. Growth-associated protein-43 IR TG neurons were also detected for 30 d after IANX, and the number of GAP-43 IR TG neurons was significantly higher in the IANX model until day 30. The relative number of large (>600 µm2) GAP-43 IR TG neurons was significantly lower, whereas the relative number of small (<400 µm2) GAP-43 IR TG neurons was significantly higher than that at day 0 until 30 d after IANX. To evaluate the functional recovery of damaged IAN, the jaw opening reflex (JOR), elicited by the electrical stimulation of the IAN, was measured before and after IANX. Jaw opening reflex occurrence was gradually increased and the relative threshold of electrical stimulation eliciting JOR was gradually decreased over the 30-d duration of the study. On day 30 after IANX, the JOR occurrence and relative JOR threshold were similar to those in sham rats. The present findings suggest that changes in the expression of GAP-43 in TG neurons after IANX are involved in regeneration and functional recovery of the transected IAN.

Ascending multisynaptic pathways from the trigeminal ganglion to the anterior cingulate cortex.

By means of retrograde transneuronal transport of rabies virus, ascending multisynaptic pathways from the trigeminal ganglion (TG) to the anterior cingulate cortex (ACC) were identified in the rat. After rabies injection into an electrophysiologically defined trigeminal projection region of the ACC, transsynaptic labeling of second-order neurons via the medial thalamus (including the parafascicular nucleus) was located in the spinal trigeminal nucleus pars caudalis. Third-order neuron labeling occurred in the TG. Most of these TG neurons were medium- or large-sized cells giving rise to myelinated Aδ or Aß afferent fibers, respectively. By contrast, TG neurons labeled transsynaptically from the orofacial region of the primary somatosensory cortex contained many small cells associated with unmyelinated C afferent fibers. Furthermore, the TG neurons retrogradely labeled with fluorogold injected into the mental nerve were smaller in their sizes compared to those labeled with rabies. Our extracellular unit recordings revealed that a majority of ACC neurons responded to trigeminal nerve stimulation with latencies of shorter than 20ms. Thus, somatosensory information conveyed to the ACC by multisynaptic ascending pathways derived predominantly from myelinated primary afferents (i.e., the medial nociceptive system) and may be used to subserve affective-motivational aspects of pain. Lack of overlap with the lateral nociceptive system is notable and suggests that the medial and lateral nociceptive systems perform separate and non-overlapping functions.

Alteration of the second branch of the trigeminal nerve activity following inferior alveolar nerve transection in rats.

After transection of the inferior alveolar nerve (IAN), the whisker pad area, which is innervated by the infraorbital nerve (ION) that was not injured, showed hypersensitivity to mechanical stimulation. Two days after IAN transection, threshold intensity for escape behavior to mechanical stimulation of the ipsilateral whisker pad area was less than 4.0 g, indicating mechanical allodynia. A total of 68 single fiber discharges were recorded from ION fibers at 3 days after IAN transection. The responses of C- and A-fibers were classified according to their conduction velocity. The C-fiber activities were not affected by IAN transection, whereas A-fiber activities were significantly enhanced by IAN transection as indicated by an increase in background activity and mechanically evoked response. Since the A-fiber responses were significantly affected by IAN transection, patch clamp recording was performed from middle to large diameter retrogradely labeled and acutely dissociated trigeminal ganglion (TRG) neurons. The I(K) (sustained) and I(A) (transient) currents were significantly smaller and hyperpolarization-activated current (I(h)) was significantly larger in TRG neurons of rats with IAN transection as compared to those of naive rats. Furthermore, current injection into TRG neurons induced high frequency spike discharges in rats with IAN transection. These data suggest that changes in K(+) current and I(h) observed in the uninjured TRG neurons reflect an increase in excitability of TRG neurons innervated by the ION after IAN transection, resulting in the development of mechano-allodynia in the area adjacent to the injured IAN innervated region.