Alteration of Primary Afferent Activity following Inferior Alveolar Nerve Transection in Rats

Abstract

BackgroundIn order to evaluate the neural mechanisms underlying the abnormal facial pain that may develop following regeneration of the injured inferior alveolar nerve (IAN), the properties of the IAN innervated in the mental region were analyzed.ResultsFluorogold (FG) injection into the mental region 14 days after IAN transection showed massive labeling of trigeminal ganglion (TG). The escape threshold to mechanical stimulation of the mental skin was significantly lower (i.e. mechanical allodynia) at 11-14 days after IAN transection than before surgery. The background activity, mechanically evoked responses and afterdischarges of IAN Aδ-fibers were significantly higher in IAN-transected rats than naive. The small/medium diameter TG neurons showed an increase in both tetrodotoxin (TTX)-resistant (TTX-R) and -sensitive (TTX-S) sodium currents (INa) and decrease in total potassium current, transient current (IA) and sustained current (IK) in IAN-transected rats. The amplitude, overshoot amplitude and number of action potentials evoked by the depolarizing pulses after 1 μM TTX administration in TG neurons were significantly higher, whereas the threshold current to elicit spikes was smaller in IAN-transected rats than naive. Resting membrane potential was significantly smaller in IAN-transected rats than that of naive.ConclusionsThese data suggest that the increase in both TTX-S INa and TTX-R INa and the decrease in IA and Ik in small/medium TG neurons in IAN-transected rats are involved in the activation of spike generation, resulting in hyperexcitability of Aδ-IAN fibers innervating the mental region after IAN transection.

Intrathecal reboxetine suppresses evoked and ongoing neuropathic pain behaviours by restoring spinal noradrenergic inhibitory tone

“…In particular, the intrathecal reuptake inhibition approach would not be expected to influence peripherally generated afferent activity from nociceptors, 10 which has been shown to be present for several weeks after nerve injury and may play a role in re-establishing central sensitisation. 34,40 Similar findings have been reported with systemic dosing of TCAs where mechanical allodynia persisted after the cessation of dosing although other measures of evoked sensitisation were attenuated. 1 It is conceivable that continuation of intrathecal dosing beyond the period of altered peripheral afferent input could prevent the subsequent development of sensitisation although this may also require that aberrant afferent barrages from the periphery have ceased in the meanwhile.…”

“…1 It is conceivable that continuation of intrathecal dosing beyond the period of altered peripheral afferent input could prevent the subsequent development of sensitisation although this may also require that aberrant afferent barrages from the periphery have ceased in the meanwhile. 34,40 The use of systemic monoamine reuptake inhibitors is established as a therapeutic strategy for chronic pain in general and neuropathic pain in particular. 4,41 Animal studies have shown that such systemic dosing increases NA levels in the spinal cord.…”

Expression of TRPV1 Channels after Nerve Injury Provides an Essential Delivery Tool for Neuropathic Pain Attenuation

“…A cell area >1000 µm 2 was considered large, while that <1000 µm 2 was considered medium and <400 µm 2 was considered small [20].…”

Chronic post-traumatic headache: clinical findings and possible mechanisms

“…46,47 Mechanical hypersensitivity accompanying trigeminal neuropathic pain involves spontaneous and low-threshold activity in injured myelinated fibers. 48 Animal models of trigeminal neuropathic pain consistently produce facial mechanical allodynia and central sensitization manifested by a reduced activation threshold and increased response to noxious and innocuous stimuli of medullary dorsal horn nociceptive neurons. 49 Thus, the spontaneous headache episodes, as well as the cranial allodynia and hyperalgesia seen in individuals with CPTHA, 17 may result from pathological changes in the cranial nerves.…”