Role of TRPV1 receptors in descending modulation of pain

Abstract

Transient receptor potential vanilloid type 1 (TRPV1) receptor is a ligand-gated non selective cation channel activated by heat (>43°), low pH and endogenous lipid molecules such as anandamide, Narachydonoyl-dopamine, N-acyl-dopamines and products of lipoxygenases (12-and 15-(S)-HPETE) termed endovanilloids. Apart from peripheral primary afferent neurons and dorsal root ganglia, TRPV1 receptor is expressed throughout the brain. Recent evidence show that TRPV1 receptor stimulation by endocannabinoids or by capsaicin within the periaqueductal grey (PAG) leads to analgesia and this effect is associated with glutamate increase and the activation of OFF cell population in the rostral ventromedial medulla (RVM). Activation of the antinociceptive descending pathway via TPRV1 receptor stimulation in the PAG may be a novel strategy for producing analgesia. This review will summarize the more recent insights into the role of TRPV1 receptor within the antinociceptive descending pathway and its possible exploitation as a target for novel pain-killer agents.

Intrathecal Administration of AS1928370, a Transient Receptor Potential Vanilloid 1 Antagonist, Attenuates Mechanical Allodynia in a Mouse Model of Neuropathic Pain

“…7) Given that TRPV1 is expressed in peripheral and central terminals of non-myelinated primary afferent neurons, and also in various brain regions, 2,12) our results suggest that AS1928370 should act on TRPV1 in these tissues.…”

Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets

“…98 Spinal cells projecting in the spino-RVM pathway predominate in laminae V, VII, VIII and X, whereas neurons of origin of the spino-PAG pathway are located in laminae I, IV-V, VI-VIII and the lateral spinal nucleus. 98 Furthermore, 'OFF'-RVM neurons mainly express NMDA/AMPA 69 and TRPV1 99 receptors. Under physiological conditions, PAG neurons release glutamate over 'OFF'-RVM neurons, causing their depolarization via NMDA/AMPA receptors.…”

Role of TRPV1 channels of the dorsal periaqueductal gray in the modulation of nociception and open elevated plus maze-induced antinociception in mice

“…Descending projections from PAG reach the rostral ventromedial medulla (RVM) and the activation of PAG-RVM pathway leads to a decrease in the perception of pain [26][27][28]. Initial studies conducted by Palazzo and colleagues concerning the putative role of TRPV1 channels within PAG-RVM descending nociceptive pathway showed that microinjection of capsaicin, a TRPV1 agonist, into the dorsal portion of the PAG (dPAG) increased the latency of nociceptive response in rats subjected to the plantar test, an acute nociceptive test [1].…”