Capsaicin-evoked release of immunoreactive calcitonin gene-related peptidefrom rat trigeminal ganglion: evidence for intraganglionic neurotransmission

Chemically-mediated cross-excitation has been described between neurons wit hin sensory ganglia. However, the identity and sourer of the chemical media tors is not known. Ca2+-dependent release of neurotransmitters from culture d sensory neurons in vitro has been observed, although neurite outgrowth ma y confound the ability to extrapolate findings from culture systems to in v ivo conditions. Thus, the present studies evaluate the hypothesis of capsai cin-sensitive intrapanglionic neuropeptide release from freshly prepared sl ices of rat sensory ganglia. The ganglionic slice preparation provides an a dvantage over neuronal cultures, because release may be assessed within min utes after tissue collection (minimizing phenotypic changes) and while main taining gross anatomical relationships. Trigeminal ganglia (TGG) were quick ly removed from male, Sprague-Dawley rats (175-200 g), chopped into 200 mum slices and placed into chambers within 3 min of collection. Chambers were perfused with buffer, and superfusates were collected and assayed for immun oreactive calcitonin gene-related peptide (iCGRP) release via radioimmunoas say. After about 90 min of baseline collection, tissue was treated with cap saicin followed by a washout period. Capsaicin (1-100 muM) evoked concentra tion-dependent increases in iCGRP release. A competitive capsaicin receptor antagonist, capsazepine, significantly inhibited capsaicin-evoked release of iCGRP. In addition, capsaicin-evoked release of iCGRP was dependent on t he presence of extracellular calcium. Furthermore, capsaicin-evoked release from TGG slices was significantly greater than that from slices of equival ent weights of adjacent trigeminal nerve shown histologically to be free of neuronal somata. These data support the hypothesis that Ca2+-dependent exo cytosis of neuropeptides may occur within the TGG in vivo and that the majo rity of this release derives from neuronal somata. (C) 2001 international A ssociation for the Study of Pain. Published by Elsevier Science B.V. All ri ghts reserved.