Neuronal Cross-talk within the Trigeminal Ganglia Contributes to Inflammatory Mechanical Allodynia

Mechanical allodynia is defined as pain caused by stimuli that do not normally evoke pain and that are mediated by the activation of low-threshold mechanoreceptive Aβ-fibers. Although mechanical allodynia is a common symptom of the neuropathic and inflammatory pain, the precise mechanisms underlying a mechanical allodynia remained to be determined. A suspected possible interaction between noxious and non-noxious sensory signal transmission pathways may play a key role in the induction of mechanical allodynia. We recently investigated possible mechanisms underlying a mechanical allodynia/neuronal changes in sensitivity at sites remote from temporomandibular joint (TMJ) inflammation by using behavioral, electrophysiological, immunohistochemical and molecular approaches. Both in-vitro and in-vivo studies revealed that under TMJ inflammation, substance P (SP) released from the Aδ-/C-trigeminal ganglion (TRG) neuronal soma (nociceptive) innervating inflamed TMJ via the paracrine mechanism play an important role in the modification of the excitability of Aβ-TRG neurons (non-nociceptive) innervating intact facial skin with up-regulated neurokinin 1 (NK1 receptors. The enhanced excitability of TMJ nociceptive TRG neurons was mainly due to the suppressing A-type voltage-gated potassium currents via a hyperpolarizing shift in the inactivation curve. These results suggest that the paracrine mechanism in the trigeminal ganglia may explain the development of the acute inflammatory mechanical allodynia without sprouting non-nociceptive fibers in the medullary dorsal horn. In other words, either NK1 receptor antagonists or A-type potassium channel openers may be therapeutic agents for the prevention of trigeminal inflammatory mechanical allodynia.