Peripheral capsaicin receptors increase in the inflamed rat hindpaw: a possible mechanism for peripheral sensitization

The vanilloid receptor-1 (VR1) is activated by capsaicin, heat and protons and is localized on primary sensory neurons. The present study investigates whether VR1 increases in the inflamed hindpaw thereby contributing to the peripheral sensitization and heat hyperalgesia that characterizes the inflamed state. Forty-eight hours after intraplantar injection of Complete Freund's Adjuvant into one hindpaw, there is a significant increase in the proportion of VR1-labeled unmyelinated axons in digital nerves in the inflamed (32.8 +/- 5.9%) compared to normal (17.1 +/- 2.6%) hindpaws (t-test, P < 0.01). A few, small diameter myelinated axons are labeled in normal and inflamed rats with no change in percentages following inflammation. The data suggest that an increase in number of unmyelinated sensory axons expressing VR1 may be one mechanism underlying peripheral sensitization of nociceptors in inflammation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.