Ablation and Regeneration of Peripheral and Central TRPV1 Expressing Nerve Terminals and the Consequence of Nociception

Abstract

Transient Receptor Potential Vanilloid 1 (TRPV1) expressed in peripheral terminals is responsible for transducing thermal and chemical nociception. Role of TRPV1 expressed in the central terminals is not clear, however, its activation modulates synaptic transmission and contributes to central sensitization. In this study, we have determined the role of TRPV1 expressed in the peripheral and central terminals using resiniferatoxin (RTX), a potent TRPV1 agonist. A single intraplantar injection of RTX, within two days induced loss of capsaicin-induced nocifensive behavior and enhanced response latency to hot plate, which recovered over a period of two months. RTX treatment resulted in the ablation of peripheral TRPV1 expressing fibers in paw skin, which regenerated over the same time period. On the other hand, a single dose of intrathecal administration of RTX, within two days caused thermal hypoalgesia. RTX treatment ablated TRPV1 expressing central sensory nerve terminals. Intriguingly, in contrast to peripheral nerve terminal regeneration that occurred within two months, the central TRPV1 expressing nerve terminals did not regenerate even after five months. The present study demonstrates that TRPV1 in the peripheral and central terminals play a role in nociception and the peripheral terminals have the ability to regenerate, whereas the central terminals do not regenerate even after five months.