TRPV1 activation alters the function of Aδ and C fiber sensory neurons that innervate bone

The Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a non-selective cation channel that is activated by capsaicin, low pH and noxious heat. It has been suggested to have a pro-algesic role in a range of conditions that present with bone pain, but the mechanisms by which this occurs are not yet clear. In this study we aimed to determine if TRPV1 is expressed in Aδ and/or C fiber bone afferent neurons, and to explore its role in the activation and/or sensitization of bone afferent neurons to mechanical stimulation. A combination of retrograde tracing and immunohistochemistry was used to determine expression of TRPV1 in the soma of bone afferent neurons that innervate the rat tibial marrow cavity. A novel, in vivo, electrophysiological bone-nerve preparation, recently developed in our laboratory, was used to make recordings of the activity and sensitivity of bone afferent neurons in response to application of the TRPV1 agonist capsaicin to the marrow cavity. We found that a substantial proportion of bone afferent neurons express TRPV1. These include both small-diameter myelinated (neurofilament rich) and unmyelinated (neurofilament poor) neurons that are likely to be Aδ and C fiber neurons, respectively. Electrophysiological recordings revealed that application of capsaicin to the marrow cavity increased ongoing activity of C fiber, and to a lesser extent Aδ fiber, bone afferent neurons. Capsaicin also sensitized both Aδ and C fiber bone afferent neurons to mechanical stimulation. This evidence supports a role for TRPV1 in the pathogenesis of pain associated with bone pathology or disease.