The peripheral neural mechanism of pain to mechanical stimuli remains elusive. C-fiber nociceptors do not appear to play a major role in mechanical pain sensation, because the stimulus-response function of mechanically sensitive C-fiber nociceptors to punctate mechanical stimuli applied to the most sensitive region in the receptive field (the hot spot) reaches a plateau at force levels insufficient to produce pain in humans. However, studies at the hot spot give an incomplete understanding of the inputs of nociceptors to the spinal cord.
View Article and Find Full Text PDFThe GABAB receptors GABAB-R1 and GABAB-R2 have been cloned in several mammalian species, and the functional receptor has been shown to exist as a heterodimeric complex. We have cloned guinea pig GABAB-R1 and GABAB-R2 receptor sequences and, using in situ hybridization and immunocytochemistry for vasopressin (AVP), we found that GABAB-R1 and -R2 receptors are expressed in vasopressin neurones of the supraoptic (SON) and paraventricular nuclei (PVN). Therefore, we used both sharp electrode and whole-cell patch recording techniques to examine the effects of the selective GABAB agonist baclofen on SON and PVN magnocellular neurones and to determine the coupling of the GABAB receptor to effector pathways.
View Article and Find Full Text PDFThe endogenous opioid neurotransmitter beta-endorphin (beta-END), a product of the proopiomelanocortin (POMC) gene, is strongly implicated in the control of the female reproductive cycle, stress responses, and antinociception. Using selective gene targeting, we have generated a strain of mice that do not express any beta-END. These mice exhibit both normal reproduction and normal basal and stress-induced hypothalamic-pituitary-axis activity, but exhibit a significantly attenuated opioid-mediated stress-induced analgesia.
View Article and Find Full Text PDFThe goal of this study was to determine the capacity of primary afferent nociceptive fibers (nociceptors) to encode information about noxious mechanical stimuli in primates. Teased-fiber techniques were used to record from 14 A-fiber nociceptors and 18 C-fiber nociceptors that innervated the hairy skin. Stimulus-response functions were examined with an ascending series of force-controlled stimuli.
View Article and Find Full Text PDFThe orphanin-FQ/nociceptin (OFQ/N) receptor (previously, ORL1, LC132) has been shown to be coupled to an inwardly rectifying K+ conductance in several neuronal populations. Although OFQ/N receptor mRNA is densely expressed in the supraoptic nucleus (SON), little is known about its coupling to effector system(s). The present study examined the effects of OFQ/N on guinea pig magnocellular neurons within the SON using intracellular recording from hypothalamic slices.
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