Peripheral inflammation selectively increases TRPV1 function in IB4-positive sensory neurons from adult mouse.
C-fiber nociceptors can be divided into two groups based on growth factor dependency and isolectin B4 (IB4) 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 microm) 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 microM 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 a novel role for IB4-positive C-fibers during inflammation.
Breese
Nicole M
NM
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
George
Annette C
AC
Pauers
Laura E
LE
Stucky
Cheryl L
CL
D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage; D002478:Cells, Cultured; D005620:Freund's Adjuvant; D006023:Glycoproteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008571:Men; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology*; D050916:TRPV Cation Channels
D006023:Glycoproteins; D007473:Ion Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C473590:isolectin B4-binding glycoprotein, mouse; D005620:Freund's Adjuvant; D002211:Capsaicin