Neuroscience
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Tight ligation of the fifth and sixth lumbar segmental nerves in the rat provides a model of neuropathic pain. We used this model to assess the changes in primary afferent input to the dorsal horn in neuropathic pain syndromes. Dorsal roots and ganglia were examined for up to 32 weeks following segmental nerve ligation. ⋯ These findings indicate that although there is a great loss of dorsal root ganglion cells, there is dramatic sprouting of myelinated fibres and possibly some sprouting of unmyelinated fibres in the dorsal roots. Additionally, a difference in the responses of unmyelinated and myelinated fibres to this peripheral nerve injury is revealed. These changes in dorsal root ganglion cells and their central axons may underlie certain aspects of abnormal pain syndromes because of changes in the types and quantity of input the dorsal horn receives.
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The expression of the transcription factor c-JUN was investigated in the rat fascia dentata under normal conditions and after entorhinal cortex lesion. As shown by immunocytochemistry and in situ hybridization histochemistry c-JUN and its messenger RNA are present in the principal cell layers of the dentate gyrus and Ammon's horn (except hippocampal region CA2). Pre-embedding immunogold electron microscopy revealed an almost exclusive nuclear localization of c-JUN, where it is associated with chromatin. ⋯ These results point to a specific role of c-JUN in the granule cells of the fascia dentata in the normal animal and in rats with entorhinal cortex lesions. The selective induction of c-JUN after entorhinal lesion could be one of the first molecular steps that regulate transneuronal changes within granule cells after their denervation. A different mechanism has to be assumed for GABAergic interneurons known to receive an entorhinal innervation as well.
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Nociceptin (a heptadecapeptide also known as orphanin FQ) is a potent endogenous agonist of the opioid receptor-like1 receptor and has a sequence similar to dynorphin A. It has been reported that intracerebroventricularly injected nociceptin produced hyperalgesia in mice and that intrathecal injection of nociceptin inhibits the spinal sensitization. In the present study, we investigated the effect of intrathecally administered nociceptin in the rat formalin test (a model of inflammatory pain) and the rat hot plate test. ⋯ These effects of nociceptin were not antagonized by the co-administration of naloxone. Intrathecal injection of nociceptin had no effect on the hot plate test. These data suggest that nociceptin plays an important role in spinal nociceptive transmission through the activation of a naloxone-insensitive receptor, and spinally administered nociceptin produces an analgesic effect during the rat formalin test, but not the hot plate test.
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Comparative Study
Presynaptic calcium channels and field-evoked transmitter exocytosis from cultured cerebellar granule cells.
Regulated exocytosis from cultured rat cerebellar granule cells can be localized by the vesicle specific marker FM2-10 to specific sites, the highest density of which are at visible varicosities coinciding with neurite-neurite contacts. Exocytosis can be evoked by uniform electrical field pulses, which initiate tetrodotoxin-sensitive action potentials, or by elevated KCl. [3H]D-Aspartate is an authentic false transmitter in this preparation, judged by sensitivity of release to bafilomycin A1 and tetanus toxin. The coupling of presynaptic voltage-activated Ca2+ channels to [3H]D-aspartate exocytosis was determined during field stimulation. ⋯ The omega-agatoxin-IVA and omega-conotoxin-GVIA inhibitions of both Ca2+ entry and exocytosis were additive and varied stochastically between individual varicosities. These results demonstrate that both Q- and P-type Ca2+ channels are highly efficient in their coupling to amino acid exocytosis, with N-type less efficient, and L-type channels not at all. The Ca2+ channel types coupled to exocytosis are also able to support exocytosis when evoked by either brief field-evoked action potentials or prolonged depolarization with KCl, indicating that these presynaptic channels, in contrast to those on the somata of the cells, can respond to widely different patterns of activation.