fMRI indicates cortical activation through TRPV1 modulation during acute gouty attacks

• Published in: Scientific reports Vol. 9; no. 1; pp. 12348 - 11
• Main Authors: Chen, Chiao-Chi, Chang, Chen, Hsu, Yi-Hua, Peng, Yi-Jen, Lee, Herng-Sheng, Huang, Guo-Shu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.08.2019; Nature Publishing Group
• Subjects: 14/63; 59; 59/36; 59/57; 631/378/2620/2618; 631/378/3917; 64; 692/308/1426; 692/308/575; 692/4023/1670/498; 82; 82/51; 82/80; Acute Disease; Animals; Arthritis; Arthritis, Gouty - diagnostic imaging; Behavior, Animal; Brain mapping; Capsaicin receptors; Cerebral blood flow; Cerebral Blood Volume; Channel gating; Disease Models, Animal; Drug development; Functional magnetic resonance imaging; Gout; Humanities and Social Sciences; Inflammation - pathology; Magnetic Resonance Imaging; multidisciplinary; Neuroimaging; Nociception; Nociceptors; Pain; Pain perception; Rats; Science; Science (multidisciplinary); Somatosensory cortex; Somatosensory Cortex - diagnostic imaging; Thalamus; Transient receptor potential proteins; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-48656-6

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.