Capsaicin Indirectly Suppresses Voltage-Gated Na+ Currents Through TRPV1 in Rat Dorsal Root Ganglion Neurons

Abstract

Available evidence indicates voltage-gated Na + channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of the biophysical and pharmacological properties of the channels in sensory neurons is largely based on the study of heterologous systems or rodent tissue, despite evidence that both expression systems and species differences influence these properties. Therefore, we sought to determine the extent to which the biophysical and pharmacological properties of VGSCs were comparable in rat and human sensory neurons. Whole cell patch clamp techniques were used to study Na + currents in acutely dissociated neurons from human and rat. Our results indicate that while the two major current types, generally referred to as tetrodotoxin (TTX)-sensitive and TTX-resistant were qualitatively similar in neurons from rats and humans, there were several differences that have important implications for drug development as well as our understanding of pain mechanisms.

TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Δ9-tetrahydrocannabiorcol

“…Our findings that activation of TRPA1 produced an initial 'depolarization block' and an extensive and sustained inhibition of voltage-gated calcium and sodium currents in DRG neurons provide a mechanism for the antinociceptive effect of spinal TRPA1 activation. This is in line with previous studies, showing that activation of TRPV1 produces a sustained inhibition of voltage-gated calcium and sodium channels [35][36][37][38][39] in sensory neurons as well as spinal antinociception 30,31,48 . On the basis of these studies, a model for TRPA1-mediated inhibition of synaptic transmission emerges, in which sodium and calcium influx through TRPA1 produces an initial depolarization-induced inactivation of voltage-gated sodium channels and a sustained inhibition of voltage-gated sodium and calcium currents, reducing action potential-dependent neurotransmitter release (Fig.…”

“…We next considered the possibility that activation of TRPA1 expressed on the central terminals of nociceptive DRG neurons inhibits the activity of voltage-gated calcium or sodium channels, thereby modifying synaptic transmission. Such mechanisms have previously been shown to operate following TRPV1 activation [35][36][37][38][39] . To assess the involvement of voltage-gated channels, we initially examined the effect of activation of TRPA1 on action potential properties and the excitability of DRG neurons in the current-clamp configuration.…”

Capsaicin Used on Skin Influences Ion Transport Pathways: An in vitro Study

“…This nonselective ligand-gated cation channel is expressed in small-diameter neurons of the dorsal root ganglion [13,14,15] and can be activated by numerous stimuli, including heat, proton, and vanilloids such as capsaicin [16,17,18,19]. Continuous application of capsaicin produced membrane depolarization but did not evoke action potentials as a result of the process of defunctionalization of nociceptor fibers [19,20,21,22,23]. For neuropathic pain syndromes, this effect was observed to last for 12 weeks after a single 30- or 60-min capsaicin 8% path topical application [10,12,24,25,26,27,28,29,30].…”

Adams Disease: Description and Management with Capsaicin and Heat

“…Endogenous agonists for TRPV1 include several endovanilloids and endocannabinoids [3]. Casaicin is an agonist for TRPV1 causing the receptor to open allowing influx of sodium and calcium [5,6]. At high enough doses, transient receptor opening is followed by long term receptor desensitization [5].…”

“…Casaicin is an agonist for TRPV1 causing the receptor to open allowing influx of sodium and calcium [5,6]. At high enough doses, transient receptor opening is followed by long term receptor desensitization [5]. This is responsible for long term pain relief.…”