| 16503963 |
Kusudo K, Ikeda H, Murase K: Depression of presynaptic excitation by the activation of vanilloid receptor 1 in the rat spinal dorsal horn revealed by optical imaging. Neuroscience. 2009 Dec 1;164(2):747-59. Epub 2009 Aug 20.
In this study, we show that capsaicin (CAP) depresses primary afferent fiber terminal excitability by acting on vanilloid receptor 1 (TRPV1 channels) of primary afferent fibers in adenosine 5'-triphosphate (ATP)- and temperature-dependent manner using two optical imaging methods. First, transverse slices of spinal cord were stained with a voltage-sensitive dye and the net excitation in the spinal dorsal horn was recorded. Prolonged treatment (> 20 min) with the TRPV1 channel agonist, CAP, resulted in a long-lasting inhibition of the net excitation evoked by single-pulse stimulation of C fiber-activating strength. A shorter application of CAP inhibited the excitation in a concentration-dependent manner and the inhibition was reversed within several minutes. This inhibition was Ca (++)-dependent, was antagonized by the TRPV1 channel antagonist, capsazepine (CPZ), and the P (2) X and P (2) Y antagonist, suramin, and was facilitated by the P (2) Y agonist, uridine 5'-triphosphate (UTP). The inhibition of excitation was unaffected by bicuculline and strychnine, antagonists of GABA (A) and glycine receptors, respectively. Raising the perfusate temperature to 39 degrees C from 27 degrees C inhibited the excitation (-3%/ degrees C). This depressant effect was antagonized by CPZ and suramin, but not by the P (2) X antagonist, 2', 3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP). Second, in order to record the presynaptic excitation exclusively, we stained the primary afferent fibers anterogradely from the dorsal root. CAP application and a temperature increase from 27 degrees C to 33 degrees C depressed the presynaptic excitation, and CPZ antagonized these effects. Thus, this study showed that presynaptic excitability is modulated by CAP, temperature, and ATP under physiological conditions, and explains the reported central actions of CAP. These results may have clinical importance, especially for the control of pain. |
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