Epidermal transient receptor potential vanilloid 1 in idiopathic small nerve fibre disease, diabetic neuropathy and healthy human subjects

Abstract

Epidermal transient receptor potential vanilloid 1 in idiopathic small nerve fibre disease, diabetic neuropathy and healthy human subjects Aims: The transient receptor potential vanilloid 1 (TRPV1) plays an important role in mediating pain and heat. In painful neuropathies, intraepidermal TRPV1 nerve fibre expression is low or absent, suggesting that pain generated is not directly related to sensory nerve fibres. Recent evidence suggests that keratinocytes may act as thermal receptors via TRPV1. The aim was to investigate epidermal TRPV1 expression in patients with neuropathic conditions associated with pain. Methods and results: In a prospective study of distal small nerve fibre neuropathy (DISN; n = 13) and diabetic neuropathy (DN; n = 12) intraepidermal nerve fibre density was assessed using the pan axonal marker PGP 9.5 and epidermal TPVR1 immunoreactivity compared with controls (n = 9). Intraepidermal nerve fibres failed to show TRPV1 immunoreactivity across all groups. There was moderate and strong TRPV1 reactivity of epidermal keratinocytes in 41.8% and 6% for DISN, 32.9% and 2.9% for DN and 25.4% and 5.1% for controls, respectively. Moderate keratinocyte TRPV1 expression was significantly increased in DISN compared with controls (P = 0.01). Conclusion: Our study suggests that in human painful neuropathies, epidermal TRPV1 expression is mainly in keratinocytes.

Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics

“…It seems quite relevant that such receptors in patients suffering from distal small nerve fiber neuropathy and diabetic neuropathy are moderately to strongly expressed on keratinocytes 49. Such receptors are also hypothesized to play a role in “people with sensitive skin” and in nociception and are hypothesized as potential new targets for the treatment of pain 50,51.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…Of note, many non-neuronal cells (e.g., urothelial cells and keratinocytes) also express pain-sensing TRP channels, in particular TRPV1 (Denda et al, 2001;Birder et al, 2002;Southall et al, 2003;Wilder-Smith et al, 2007), TRPV3 (Facer et al, 2007), and TRPV4 (Chung et al, 2003;Gevaert et al, 2007). It has been also suggested (reviewed in Moran et al, 2011) that these cells may also function as unconventional (non-neuronal) pain sensors and communicate with polymodal nociceptive C fibers (Southall et al, 2003;Birder, 2005).…”

NGX-4010, a Capsaicin 8% Dermal Patch, for the Treatment of Painful HIV-associated Distal Sensory Polyneuropathy

“…13 Capsaicin is a highly selective agonist of transient receptor potential vanilloid 1 (TRPV1), a ligand-gated, nonselective cation channel highly expressed on C-fiber and Ad-fiber nociceptors. 14 As altered expression of TRPV1 may play a role in NP conditions, [15][16][17][18] targeting TRPV1 is a rational approach for managing NP. After topical application, capsaicin results in the reversible defunctionalization and reduction of epidermal nerve fibers, leading to long-lasting inhibition of pain transmission.…”