TRPV1 and TRPA1 Function and Modulation Are Target Tissue Dependent

Abstract

The NGF and GDNF families of growth factors regulate the sensitivity of sensory neurons. The ion channels TRPV1 and TRPA1 are necessary for development of inflammatory hypersensitivity and are functionally potentiated by growth factors. We have shown previously that inflamed skin exhibits rapid increases in artemin mRNA with slower, smaller increases in NGF mRNA. Here, using mice we show that in inflamed colon, mRNA for both growth factors increased with a pattern distinct from that seen in skin. Differences were also seen in the pattern of TRPV1 and TRPA1 mRNA expression in DRG innervating inflamed skin and colon. Growth factors potentiated capsaicin (a specific TRPV1 agonist) and mustard oil (a specific TRPA1 agonist) behavioral responses in vivo, raising the question as to how these growth factors affect individual afferents. Because individual tissues are innervated by afferents with unique properties, we investigated modulation of TRPV1 and TRPA1 in identified afferents projecting to muscle, skin and colon. Muscle and colon afferents are twice as likely as skin afferents to express functional TRPV1 and TRPA1. TRPV1 and TRPA1 responses were potentiated by growth factors in all afferent types, but compared to skin afferents, muscle afferents were twice as likely to exhibit NGF-induced potentiation and half as likely to exhibit artemin-induced potentiation of TRPV1. Furthermore, skin afferents showed no GDNF-induced potentiation of TRPA1, but 43% of muscle and 38% of colon afferents exhibited GDNF-induced potentiation. These results show that interpretation of afferent homeostatic mechanisms must incorporate properties that are specific to the target tissue.

Physiological, pharmacological, and behavioral evidence for a TRPA1 channel that can elicit defensive responses in the medicinal leech

“…of these two TRP channels in mammals (Salas et al, 2009;Malin et al, 2011). The range of AITC used on the leeches is well within the range of concentrations used experimentally in mammals and invertebrates for eliciting nocifensive responses (Jordt et al, 2004;Kang et al, 2010;Weller et al, 2011).…”

Physiological temperatures drive glutamate release onto trigeminal superficial dorsal horn neurons

“…Knowledge of the degree of synaptic convergence of such afferent nerves is limited in Vc but the varied thermal and CAP responses could reflect these diverse sources (Zanotto et al 2007). Combining anatomic approaches with patch-clamp recordings may help identify distinct Vc synapses and pathways (Gracheva et al 2011;Malin et al 2011).…”

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

“…Acute exposure of colonic afferent neurons to NGF potentiates TRPV1-and TRPA1-evoked Ca 2+ signaling in colonic afferents, suggesting an important role for TrkA receptor signaling in TRP channel activity, potentially due to increased TRP channel surface expression (Zhang et al, 2005). Similarly, glial-derived neurotrophic factor-mediated sensitization of TRPA1 has been investigated in cutaneous afferents and shows no sensitization, thus highlighting the functional importance of peptidergic neurons in neurogenic inflammation (Malin et al, 2011).…”