Journal
PAIN
Volume 115, Issue 1-2, Pages 37-49Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.pain.2005.02.010
Keywords
VR1; ASIC; protons; capsaicin; nociceptor; C fiber
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C-fiber nociceptors can be divided into two groups based on growth factor dependency and isolectin 134 (1134) binding. IB4-negative nociceptors have been proposed to contribute to inflammatory pain. Since the TRPV1 receptor is critical for inflammatory heat hyperalgesia, we hypothesized that inflammation would sensitize IB4 negative but not IB4-positive small-diameter neurons to TRPV1 Stimuli. Two days after complete Freund's adjuvant (CFA)-induced inflammation in the hind paw of mice, lumbar 4/5 ganglia were dissociated and small-diameter (<= 26 mu m) neurons were quantified for responsiveness to the TRPV1 agonists, capsaicin and protons using patch clamp recordings. surprisingly. inflammation did not alter the responsiveness of IB4-negative neurons to capsaicin or protons. Conversely, inflammation increased the percentage of IB4-positive neurons that responded to 1 mu M capsaicin from 24 to 80% and increased the percentage that responded to pH 5.0 from 54 to 85%. In parallel, inflammation increased the percentage of IB4-positive neurons that was TRPV1-immunoreactive. The inflammation-induced increase in capsaicin- and proton-responsiveness was entirely mediated by TRPV1 because IB4-positive neurons from inflamed TRPV1-/- mice were capsaicin-insensitive and unaltered in proton-responsiveness. Interestingly, comparison of neurons from TRPV1+/+ and TRPV1-/- mice revealed that the sustained proton-evoked currents in IB4-positive neurons were independent of TRPV1 whereas the sustained-only proton currents in IB4-negative neurons were TRPV1-dependent. Together, these data indicate that TRPV1 function and expression are selectively increased in IB4-positive neurons during inflammation in Mouse and suggest an ovel role for IB4-positive C-fibers during inflammation. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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