Neuroscience
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The cornea is innervated by three functional types of neurons: mechanosensory, polymodal and cold-sensitive neurons, all of which are presumed to be nociceptive. To explore if corneal neurons constitute a heterogeneous population according to their electrophysiological properties, intracellular recordings were made in vitro from trigeminal ganglion neurons innervating the cornea of the mouse. Corneal neurons were labelled with FluoroGold applied after a corneal epithelial wound. ⋯ Neurons with a slower action potential showing a hump in the repolarization phase are both corneal Adelta and C polymodal nociceptive neurons, a type of cell in which tetrodotoxin-resistant Na(+) channels have been identified. The possibility is raised that the small population of neurons with a very high input resistance are cold-sensitive neurons. From the present results, we suggest that the electrophysiological properties of primary sensory neurons innervating the cornea are attributable not only to their conduction velocities, but also to the functional characteristics of their peripheral nerve terminals.
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Nociceptin receptors are densely distributed in the nucleus tractus solitarius pre- and postsynaptically. This study tested whether nociceptin receptors in this brain area are involved in the modulation of baroreceptor reflex. In pentobarbital-anesthetized rats, pharmacological activation of nociceptin receptors with bilateral microinjection of a synthetic peptide agonist, nociceptin, into the nucleus tractus solitarius attenuated baroreflex sensitivity as demonstrated by a marked reduction in baroreflex bradycardia induced by a single dose of intravenous phenylephrine. ⋯ In contrast, injection of an opioid receptor antagonist, naloxone (5nmol), did not modify the inhibition of baroreflex sensitivity induced by nociceptin. Neither nocistatin nor naloxone injected into the nucleus alone had any detectable effect on baseline blood pressure and heart rate and baroreflex bradycardia. These data indicate that the newly discovered nociceptin receptors in the central nervous system possess an inhibitory influence on baroreflex transmission at the level of the nucleus tractus solitarius.
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Partial injury of the rat sciatic nerve elicits a variety of characteristic chemical, electrophysical and anatomical changes in primary sensory neurons and constitutes a physiologically relevant model of neuropathic pain. To elucidate molecular mechanisms that underlie the physiology of neuropathic pain, we have used messenger RNA differential display to identify genes that exhibit increased ipsilateral expression in L4/5 dorsal root ganglia, following unilateral partial ligation of the rat sciatic nerve. ⋯ Induction of nerve injury-associated kinase expression in dorsal root ganglia in the rat neuropathic pain model was confirmed by quantitative reverse transcription-polymerase chain reaction, and RNA in situ hybridization analysis revealed enhanced levels of nerve injury-associated kinase within neurons. Together, our data implicate nerve injury-associated kinase as a novel upstream component of an intracellular signalling cascade that is up-regulated in dorsal root ganglia neurons in response to sciatic nerve injury.
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The effects of different hormone replacement regimens on basal forebrain cholinergic function were examined by measuring changes in choline acetyltransferase activity and high affinity choline uptake in adult, ovariectomized, rats. Increases in choline acetyltransferase activity were detected in the frontal cortex (20. 1%) and olfactory bulbs (30.4%) following two weeks, but not four weeks, of repeated treatment with estrogen plus progesterone. Increases in high affinity choline uptake were detected in the frontal cortex (39.5-55.1%), hippocampus (34.9-48.9%), and olfactory bulbs (29.9%) after two weeks, but not four weeks, of either continuous estrogen administration, repeated progesterone administration, or repeated treatment with estrogen plus progesterone. ⋯ The findings demonstrate that short-term treatment with estrogen and/or progesterone can significantly enhance cholinergic function within specific targets of the basal forebrain cholinergic projections. Most important is the fact that the effects varied considerably according to the manner and regimen of hormone replacement and did not persist with prolonged treatment. These findings could have important implications for the effective use of hormone replacement strategies in the prevention and treatment of Alzheimer's disease and age-related cognitive decline in women.