Cellular Basics For The Effects Of Rsnsr1 And 5-ht_2a Receptors On Nociception

It has been demonstrated that rSNSRl and 5-HT2A receptors play an important role in, respectively, modulation of morphine-mediated antinociception and hyperalgsia induced by peripheral inflammation. Some studies further suggested that certain signaling molecules, such as nitric oxide (NO), calcitonin gene-related protein (CGRP) and protein kinase C (PKC) may be involved in their peripheral regulation. However, most of their co-locations with rSNSRl or 5-HT2A receptor remain unclear in dorsal root ganglion. The present study introduced several experimental approaches like tissue culture, ELISA (enzyme linked immunosorbent assay) and immunofluorescence double-labeling to explore both NO and PKCεpathway in rSNSRl function and PKCs pathway in 5-HT2A action.In vitro study, up-regulation of CGRP in the co-cultured DRG and TG tissue was shown by consecutive treatment of selective rSNSR1 agonist (BAM8-22) for 4 days, which can be stimulated by a combined treatment of L-NAME, a non-selective nitric oxide synthesis inhibitor. Result from double-labeling shown that nNOS expression was restricted into the rSNSRl positive neurons in DRG in rat. These neurons were small-and medium-sized cells. And it also provided evidence that rSNSR1 and PKCεco-existed in some DRG neurons. With regard to 5-HT2A receptor and PKCε, most of the cells co-expressed them were small- and medium-sized neurons.These results provided the cellular evidence for our previous observations such as chronic activation of rSNSR1 resulted in the enhanced expression of CGRP and the reduced analgesic effect of morphine, as well as the involvement of PKCεpathway in the 5-HT2A receptor-mediated inflammatory hyperalgesia.