fMRI indicates cortical activation through TRPV1 modulation during acute gouty attacks

Abstract

Gout is one of the most painful disease conditions. The central mechanism of pain processing in this condition remains elusive. Cerebral blood volume (CBV) responses are faithful correlates of brain activity changes; the application of CBV-weighted functional magnetic resonance imaging (fMRI) may shed light on the issue of interest. Transient receptor potential vanilloid 1 (TRPV1) is a critical ion channel expressed both peripherally in nociceptors and centrally in the brain. Whether TRPV1 plays a critical role in gout pain was also explored. Results showed that, in rats with gouty arthritis, noxious stimulation induced CBV increases in the primary somatosensory cortex and thalamus. These increases were correlated with up-regulated TRPV1 protein expression and pain behavior. Selective blockage of central TRPV1 channel activity by intrathecal administration of AMG9810 reversed the induced pain, and abolished the induced CBV increase in thalamocortical regions. The findings support that TRPV1 activation in the central pain pathway is crucial to the augmentation of pain in gouty conditions. This new information supports the development of TRPV1-based drugs for treating gout pain, while fMRI can be useful for repeated evaluation of brain activity changes induced by gout.

N-Methylamide-structured SB366791 derivatives with high TRPV1 antagonistic activity: toward PET radiotracers to visualize TRPV1

“…Higher accumulation was observed in the striatum, thalamus, hypothalamus, and medulla, as well as in the widespread cortical area, which closely correlates with observations in previous in vitro studies on mouse or rat TRPV1 in the central nervous system. 28–33 Concerning [ 11 C] 2 , uptake in the cerebellum was rarely observed. Impressively, Fig.…”

Roles of TRP and PIEZO receptors in autoimmune diseases

“…This increase correlates with the upregulation of TRPV1 protein expression and pain behaviour. Selective blockade of central TRPV1 channel activity by intrathecal administration reverses the induced pain and abrogates the cerebral blood volume increase in the thalamocortical region (Refs 123, 124).…”

Transient receptor potential vanilloid 1: A potential therapeutic target for the treatment of osteoarthritis and rheumatoid arthritis

“…103,114 The intrathecal injection can achieve the same analgesic effect as an intra-articular injection, and intrathecal injection can also alleviate the pain caused by local inflammatory factors within the joint and surrounding soft tissues. 176 Intraarticular therapeutic strategies appear well suited for the management of OA, in particular, the knee OA. Intra-articular RTX suppressed the carrageenan-induced oedema by at least one-third, and its smaller therapeutic dose was approximately 1000 times lower than the dose producing analgesia following systemic administration of RTX in rats.…”

“…Some drugs (e.g., A‐425619 and A‐795614) have low central nervous system penetration, so intrathecal analgesia is better than oral administration 103,114 . The intrathecal injection can achieve the same analgesic effect as an intra‐articular injection, and intrathecal injection can also alleviate the pain caused by local inflammatory factors within the joint and surrounding soft tissues 176 . Intra‐articular therapeutic strategies appear well suited for the management of OA, in particular, the knee OA.…”