Defining Neuronal Function And Phenotype Within The Trigeminal Nervous System

Objectives: Chronic orofacial pain conditions are common in the Western world. Trigeminal neurons constitute the first link in nociceptive information processing within the orofacial region. They innervate distinct target tissues and respond to a range of pathological insults. Many chronic orofacial pain conditions result from inflammation within tissues surrounding the peripheral terminals of trigeminal nociceptors and associated inflammatory mediators provide a mechanism for direct interaction between the immune and nervous systems. Furthermore, evidence suggests that the properties of trigeminal nociceptors and their responses to peripheral inflammation may be distinct from those of spinal nociceptors. These observations have prompted us to examine presumptive neuronal function within the TG based upon neurochemical phenotype, the distribution of expression of receptor components for three major inflammatory mediators (NGF, IL-6, TNF-alpha) and their co-expression within these presumptive functional phenotypes.

Methods: Indirect dual immunofluorescence was performed on uninjured adult rat trigeminal ganglion (TG) and dorsal root ganglion (DRG).

Results: A significantly higher proportion of neurons express NF200-IR in TG compared to DRG (p=<0.001) and a significantly lower proportion of neurons express CGRP-IR (p=<0.01) and IB4-IR (p=<0.001) in TG compared to DRG. Within these neurochemical populations, significant differences were also found in levels of co-expression for TrkA (p=<0.01) and p55 (p=<0.01) in TG compared to DRG. A significantly lower proportion of neurons express TRPV1-IR in TG compared to DRG (p=<0.05). Co-expression of NF200/TRPV1 was also significantly lower in TG compared to DRG (p=<0.05).

Conclusion: Based upon neurochemical data this indicates significant differences in relative proportions of functional neuronal phenotypes between TG and DRG that may reflect unique target innervation within the orofacial region. Furthermore these data indicate that in the TG, sensory neurons displaying both nociceptive and non-nociceptive neurochemical phenotypes may be potential targets for direct activation by several important pro-inflammatory mediators.