Voltage-gated sodium channel expression in rat nodose ganglion before and after capsaicin lesion

Rose Marie Tello Larios

The nodose ganglion (NG) contains the cell bodies of vagal afferent neurons, which transmit visceral sensory information from thoracic and abdominal organs to the brain. The expression of Na+ current, a key determinant of neuronal excitability, in NG has been characterized electrophysiologically but little is known about the distribution of specific voltage-gated sodium channel (Nav) subtypes amongst subpopulations of NG neurons. The expression of tetrodotoxinsensitive Nav1.3 and tetrodotoxin-resistant Nav1.8 in sensory neurons is differentially altered following various peripheral nerve injuries. Deafferentation by systemic capsaicin treatment results in loss of capsaicin-sensitive neurons and proliferation of new neurons; therefore we hypothesized that Nav1.3 expression would increase and Nav1.8 would decrease in nodose neurons following deafferentation. We utilized quantitative real-time PCR and immunohistochemistry on rat whole nodose ganglia collected 3, 11 and 42 days following capsaicin treatment to measure gene and immunoreactivity changes of Nav1.3, Nav1.8 and TRPV1 (the capsaicin receptor). Additionally, we performed single-cell PCR analysis from cultured nodose neurons extracted 11 days following treatment to determine neuronal phenotypes. We report a significant increase in Nav1.3 mRNA expression 11d (p=0.03) but not 3d or 42d following capsaicin lesion. Additionally, Nav1.8 and TRPV1 expression significantlydecreases at 3d and 11d post-lesion and recovers by 42 days. The number of neurons expressing Nav1.3, Nav1.8 and TRPV1 mRNA were reduced to 0% (p=0.008), 22.7% (p=0.091) and 4.5% (p=0.001), respectively, following capsaicin treatment, compared to 27%, 50%, and 50% in controls. Analysis of single nodose neurons revealed that Nav1.3 mRNA was localized in TRPV1-positive and Nav1.8-positive neurons in controls but not in capsaicin-lesion animals. Additionally, Nav1.8 co-expressed with TRPV1-positive neurons in controls but following capsaicin treatment, was primarily expressed in TRPV1-negative neurons. Taken together, this data provides evidence for neuronal plasticity - specifically with respect to expression of certain voltage-gated sodium channels - following deafferentation.

Voltage-gated sodium channel expression in rat nodose ganglion before and after capsaicin lesion

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