Neuroscience letters
-
Neuroscience letters · Nov 2003
Randomized Controlled Trial Comparative Study Clinical TrialDose ratio is important in maximizing naloxone enhancement of nalbuphine analgesia in humans.
The analgesic effect of kappa partial agonist opioids (i.e. nalbuphine, pentazocine and butorphanol) is significantly greater in women. Recent evidence suggests that this sexual dimorphism may result from a naloxone-sensitive anti-analgesic effect that is activated along with, and summates with, the analgesic effect of these agents, resulting in decreased analgesia or increased pain. For example, nalbuphine (5 mg) produces profound anti-analgesia (i.e. enhanced pain) in men, but addition of a low dose of the opioid receptor antagonist naloxone (0.4 mg, opioid antagonist) induces significant analgesia in men and enhances nalbuphine analgesia in women. ⋯ In the current study, we tested the hypothesis that an important determinant of naloxone enhancement of nalbuphine analgesia is the dose ratio of nalbuphine to naloxone. Since a dose ratio of 12.5:1 (i.e. 5 mg nalbuphine:0.4 mg naloxone) resulted in analgesic enhancement, but a dose ratio of 6.25:1 (2.5 mg:0.4 mg) did not, we tested the same, lower, dose of nalbuphine (2.5 mg) in combination with a lower dose of naloxone (0.2 mg) to maintain the 12.5:1 dose ratio. This lower dose of naloxone significantly prolonged the analgesic effect of nalbuphine in both men and women, suggesting that the anti-analgesic effect of nalbuphine is present in both sexes at the 2.5 mg dose and that the dose ratio of nalbuphine to naloxone is an important determinant of the analgesic efficacy of this combination.
-
Neuroscience letters · Oct 2003
Comparative StudyEffect of systemic FR140423, a new analgesic compound, in a rat model of postoperative pain: contribution of delta-opioid receptors.
We investigated the anti-hyperalgesic effect of FR140423, 3-(difluoromethyl)-1-(4-methoxyphenyl-5-[4-(methylsulfinyl)phenyl]pyrazole, in a rat model of postoperative pain. Oral administration of FR140423 at doses between 1 and 100 mg/kg after surgery dose dependently attenuated the punctate mechanical hyperalgesia caused by an incision of the plantar surface of the hind paw with an ED50 value of 59 mg/kg. The anti-hyperalgesic effect of systematically administered FR140423 was blocked by naloxone, a non-selective opioid receptor antagonist. ⋯ Naloxonazine and nor-binaltorphimine failed to antagonize the anti-hyperalgesic effect of FR140423. The action of FR140423 differs from the naloxonazine-reversible anti-hyperalgesia induced by morphine. The present findings suggest that delta-opioid systems play a role in the rat anti-hyperalgesia produced by FR140423 for postoperative pain characterized by mechanical hyperalgesia.
-
Neuroscience letters · Oct 2003
Comparative StudyFree fatty acids in cerebrospinal fluids from patients with traumatic brain injury.
Free fatty acid (FFA) concentrations in cerebrospinal fluid (CSF) are recognized as markers of brain damage in animal studies. There is, however, relatively little information regarding FFA concentrations in human CSF in normal and pathological conditions. ⋯ Higher concentrations of total polyunsaturated fatty acids (P<0.001) and of arachidonic, myristic and palmitic acids measured individually in CSF (P<0.01) obtained 1 week after the insult were associated with a worse outcome at the time of hospital discharge using the Glasgow Outcome Scale. This preliminary investigation suggests that CSF FFA concentrations may be useful as a predictive marker of outcome following TBI.
-
Neuroscience letters · Sep 2003
N-methyl-D-aspartate receptor subunit expression and phosphorylation following excitotoxic spinal cord injury in rats.
The role of NMDA receptor expression and post-translational modification in the pathological and behavioral consequences of injury were examined in rats receiving spinal injections of quisqualate. Spinal cords were removed 3 days following the development of excessive grooming behavior or, if the spontaneous pain-like behavior was not observed, 13 days following injections. Western blots from the spinal tissue demonstrated that non-grooming animals had elevated protein levels of the NR1 subunit of the NMDA receptor. ⋯ NR1 protein in grooming rats was not elevated, but there was a significant increase in NR1 serine phosphorylation. These findings suggest that excitotoxic lesions of the spinal cord induce both NR1 expression and NR1 serine phosphorylation. However, the injury-induced excessive grooming behavior is only associated with phosphorylation of the NR1 subunit.
-
Neuroscience letters · Sep 2003
Comparative StudyMotor control and children with autism: deficit of anticipatory function?
This study aims at investigating how do anticipatory postural adjustments develop in children with autism, during a bimanual load-lifting task that required maintaining the stabilisation of the forearm despite imposed or voluntary unloading. Elbow angle and electromyographic were recorded on the child forearm supporting the load. ⋯ These results indicate the use of a feedback rather than a feed-forward mode of control. Impairments in both the building of internal representations and the mastering of timing parameters, could explain the deficient postural anticipation reported in children with autism.