Neuroscience
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This study examined the contribution of endogenous opioids to the antinociception produced by microinjection of the GABAA receptor antagonist, bicuculline, into the rat midbrain ventrolateral periaqueductal gray region. Microinjection of bicuculline (40 ng/0.4 microliter) into the periaqueductal gray produced robust antinociception as measured by the tail-flick latency to noxious heat. This antinociception was partially reversed by intravenous administration of the non-selective opioid antagonist naloxone hydrochloride (1 and 5 mg/kg), indicating that endogenous opioid release is necessary for this effect. ⋯ None of the antagonists altered baseline tail-flick latencies. These results support the hypothesis that a population of periaqueductal gray neurons produces antinociception through a mu-opioid receptor-mediated action of endogenous opioids in the rostral ventromedial medulla. Thus, two opioid-sensitive pain-modulating brainstem sites are linked by an endogenous opioid synapse in the rostral ventromedial medulla.
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Several recent studies have demonstrated that expression of the tumour-suppressor gene p53 increases within the nervous system after injury. In various cell lines wild-type-p53, induced by DNA damage, has been shown to function to halt cell-cycle progression and under certain circumstances to induce programmed-cell death or apoptosis. Since wild type-p53 can act as a transcription factor to regulate the expression of p53-responsive genes it is possible that either, or both, functions of p53 are mediated by down-stream effector genes. ⋯ These results suggest that p53 protein may function as an active transcription factor in lesioned brain perhaps initiating the re-expression of Bax in injured brain regions. However, since Gadd-45 precedes p53 expression it appears unlikely that p53 is involved in regulating the early expression of Gadd-45. Taken together however, these results suggest that p53, Bax and Gadd-45 may play important roles in the response (damage/recovery) of the brain following excitotoxic injury.
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Prostaglandins sensitize some nociceptors to noxious mechanical, thermal and chemical stimuli; however, not all nociceptors are sensitized by prostaglandins. We used cultures of dorsal root ganglion neurons from neonatal rats to determine whether prostaglandins differentially alter the responsiveness of populations of neurons to the chemical stimulus bradykinin. Groups of dorsal root ganglion neurons were defined by size of the cell soma and by the presence of immunoreactivity for substance P. ⋯ These results support the hypothesis that prostaglandin E2 sensitizes some normally unresponsive primary afferent neurons to chemical stimuli. One population of neurons which becomes responsive to bradykinin after treatment with prostaglandin E2 can be defined based on cell size, and furthermore, these neurons are likely to express substance P. During inflammation, recruitment of primary afferent neurons that are immunoreactive for substance P would enhance the participation of substance P in central mechanisms that contribute to hyperalgesia.