Neuroreport
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The N-methyl-D-aspartate (NMDA) and cholecystokinin (CCK)-B receptors may have a role in the development and reversal of tolerance to morphine. In morphine-tolerant rats, addition of the CCK-B receptors antagonist CI 988 or the NMDA receptor blocker dextromethorphan enhanced the antinociceptive effect of morphine on the hot plate test. ⋯ In drug-naive rats, dextromethorphan by itself had no antinociceptive effect, but when combined with morphine or morphine and CI 988, it significantly potentiated the magnitude and duration of the effect of morphine. Thus, unlike the reversal of tolerance with CI 988 at doses that did not potentiate the effect of morphine, the antinociception observed with the NMDA antagonist in the presence of morphine in tolerant rats may not represent the reversal of tolerance, but may instead reflect the potentiation of morphine's analgesic effect by dextromethorphan.
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Clinical Trial
Mechanisms of allodynia: interactions between sensitive mechanoreceptors and nociceptors.
We examined whether stimulation of sensitive mechanoreceptors from an area of allodynia evokes nociceptor activity expressed as axon reflexes. Experiments were conducted on human volunteers. Cutaneous blood flow was measured with a laser Doppler flowmeter. ⋯ The same stimulation in areas of allodynia evoked pain as well as axon reflexes. Cooling the area of primary hyperalgesia or blocking the A fibres in the nerve that innervated the allodynia area abolished the allodynia and the axon reflex. These results demonstrate central interactions between sensitive mechanoreceptors and nociceptors concomitant with the development of allodynia.
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The aim of this study was to quantitate imidazoline receptors in postmortem brains of heroin addicts who died of an opiate overdose. The density of I2-imidazoline receptors ([3H]idazoxan binding in the presence of adrenaline) and the immunoreactivity of the related 29/30 kDa imidazoline receptor protein were decreased (39% and 28%, respectively) in the frontal cortex. The density of brain I2-imidazoline receptors was also decreased in heroin-dependent rats (27%). This novel finding indicates that opiate addiction induces down-regulation of I2-imidazoline receptors in astrocytes, and presumably down-regulation of the functions associated with these receptors.
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This study evaluated treatment with riluzole, a neuroprotective agent, following thoracic spinal cord compression in the rat. Animals received riluzole (2 mg kg-1) or vehicle twice daily for 10 days following the trauma. Motor deficits, somatosensory evoked potentials (SEP) and lesion histology were evaluated. ⋯ Trauma dramatically disturbed SEPs with falls in amplitude and increases in latency. After riluzole SEP returned towards pre-injury levels, while untreated animals showed no recovery. Morphological studies revealed significant (53%) reduction in the degree of spinal cord infarcted after riluzole treatment.
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This study was carried out to determine both the effect of systemic paracetamol on the C-fibre evoked reflex activity, a test sensitive to centrally acting analgesic drugs, and the influence of an intrathecally administered 5HT3 receptor antagonist, tropisetron. Paracetamol (200, 300, 400 mg kg-1, i.v.) dose-dependently decreased (maximal effects -60 +/- 8%) the C-evoked responses for a duration of 90 min (for the lowest dose). This effect was totally suppressed by tropisetron (1 microgram, i.t.). These data confirm previous studies suggesting a central effect of this drug and demonstrate the involvement of a spinal 5HT3 mediated serotonergic mechanism.