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.
Highlights
As one of the most painful disease conditions, gout is characterized by episodes of severe pain, tenderness, warmth, redness, swelling as well as fever[1] in the affected tissue
The left wrist was deposited with monosodium urate crystals (MSU) for the induction of gouty arthritis whereas the right wrist was treated with saline serving as the control
Pain scores and wrist diameters were statistically analyzed as shown in Fig. 1D, and the results of this analysis indicated that overt signs in this rat model of gouty arthritis were the most severe at 3 hr
Summary
As one of the most painful disease conditions, gout is characterized by episodes of severe pain, tenderness, warmth, redness, swelling as well as fever[1] in the affected tissue. Our hypothesis is that gout-induced change in nociceptive pathway activity may be mediated by an ion channel such as TRPV1, and results in exacerbation of pain. The involvement of TRPV1 in gout pain was confirmed pharmacologically using a TRPV1-selective blocker called AMG9810 These findings established the involvement of a TRPV1-mediated nociceptive mechanism in the augmentation of pain responses in gout. Such new information may support the development of TRPV1 antagonists as new drugs for treating gout, while fMRI can be used diagnostically for evaluating gout pain in the brain
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
