Neuroscience
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Neuropathic pain resulting from peripheral nerve injury can often be relieved by administration of alpha-adrenergic receptor antagonists. Tonic activation of alpha-adrenergic receptors may therefore facilitate the hyperalgesia and allodynia associated with neuropathic pain. It is currently unclear whether alpha2A- or alpha2c-adrenergic receptor subtypes are involved in the pro-nociceptive actions of alpha-adrenergic receptors under neuropathic conditions. ⋯ Increased expression of neuropeptide Y correlated with changes in mechanical sensitivity. The decrease in alpha2A-adrenergic receptor immunoreactivity and the lack of consistent changes in alpha2C-adrenergic receptor immunoreactivity suggest that neither of these receptor subtypes is likely to be responsible for the abnormal adrenergic sensitivity observed following nerve injury. On the contrary, the decrease in alpha2A-adrenergic receptor immunoreactivity following nerve injury may result in an attenuation of the influence of descending inhibitory noradrenergic input into the spinal cord resulting in increased excitatory transmitter release following peripheral stimuli.
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The effects of the mu-receptor agonist fentanyl on extracellular levels of dopamine in rat nucleus accumbens were studied in awake animals by in vivo brain microdialysis. Fentanyl dose-dependently increased the levels of dopamine when given intravenously (microg/kg) or via a microdialysis probe placed into the ventral tegmental area or the nucleus accumbens (nmol). The effect of fentanyl given into the nucleus accumbens was blocked by systemic administration of the non-selective opioid receptor antagonist naloxone and by accumbens administration of D-Phe-Cys-Tyr-D-Trp-Om-Thr-Phe-Thr-NH2 (nmol), a mu-opioid receptor antagonist, and naltrindole (nmol), a non-selective delta-opioid receptor antagonist, in a dose-dependent manner. ⋯ Administration of the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4,Gly5-ol]-enkephalin (nmol), the delta1-opioid receptor agonist [D-Pen2,5]-enkephalin (nmol) or the delta2-opioid receptor agonist [D-Ala2,Glu4]-deltorphin (nmol) into the nucleus accumbens enhanced the amount of accumbal dopamine. This study provides evidence that not only activation of delta1- and delta2-opioid receptors, but also activation of mu-opioid receptors in the nucleus accumbens increases the release of accumbal dopamine in freely moving rats. We suggest that the effect of intra-accumbens administration of fentanyl upon accumbal release of dopamine is either due to the simultaneous activation of mu-opioid receptors and delta2-opioid receptors or due to activation of mu-opioid receptors that interact with delta2-opioid receptors in a complex manner.
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Inflammation and hyperalgesia induce a dramatic up-regulation of opioid messenger RNA and peptide levels in nociceptive neurons of the spinal dorsal horn. Descending axons modulate nociceptive transmission at the spinal level during inflammatory pain, and may play a role in the development of persistent pain. The role of descending bulbospinal pathways in opioid-containing nociceptive neurons was examined. ⋯ These data suggest that increased dynorphin messenger RNA ipsilateral to inflammation, in rats without descending axons, was due to increased expression within the same cells and not to recruitment of additional dynorphin-expressing cells. This reflects a greater dynamic response of nociceptive neurons to noxious stimuli in the absence of descending modulation. Therefore, the net effect of descending afferents on spinal nociceptive circuits may be to reduce the response of opioid-containing neurons to noxious stimulation from the periphery.
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In previous studies we have shown that electrical stimulation of the nucleus submedius inhibits the rat radiant heat-induced tail flick reflex, and that this antinociceptive effect is mediated by the ventrolateral orbital cortex and periaqueductal gray. The aim of the present study was to examine whether electrical stimulation of the nucleus submedius could inhibit the rat jaw-opening reflex, and to determine whether electrolytic lesions of the ventrolateral orbital cortex or the periaqueductal gray could attenuate the nucleus submedius-evoked inhibition. Experiments were performed on pentobarbital-anesthetized rats. ⋯ The onset of inhibition occured 60 ms after the beginning of nucleus submedius stimulation and lasted about 100 ms, as determined by varying the conditioning-test time interval. Furthermore, ipsilateral lesions of the ventrolateral orbital cortex or bilateral lesions of the lateral or ventrolateral parts of periaqueductal gray eliminated the nucleus submedius-evoked inhibition of the jaw-opening reflex. These data suggest that the nucleus submedius plays an important role in modulation of orofacial nociception, and provide further support for a hypothesis that the antinociceptive effect of nucleus submedius stimulation is mediated by ventrolateral orbital cortex and activation of a descending inhibitory system in the periaqueductal gray.
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The amygdala is a complex forebrain structure proposed to play a pivotal role in fear conditioning circuitry. In this study, c-Fos immunomapping was applied to investigate the functional activation of particular amygdalar nuclei following a 50-trial training session of two-way active avoidance reaction. To dissect distinctive responses displayed by the animals and to cluster them into groups of correlated behaviors, factor analysis was employed. ⋯ The expression in the cortical nucleus correlated negatively with grooming behavior, whereas c-Fos immunolabeling of the other three subdivisions of the amygdala could be associated with the number of intertrial responses. No correlation was observed between c-Fos expression and avoidance reactions performed or the amount of shock received by the animal. The results obtained with c-Fos mapping of various regions of rat amygdala, combined with a fine dissection of behavioral repertoire, imply that there are specific functional links between particular parts of the structure and distinctive behaviors that reflect various emotional states of the animal.