Brain research
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A model of subarachnoid hemorrhage (SAH) first described in rats where blood is injected into the prechiasmatic cistern was adapted to mice. The hypothesis was that such an anterior circulation SAH model would produce vasospasm of greater severity and longer duration than other mouse models. The goal was to create a mouse model that could then be used in transgenic and knockout animals in order to further knowledge of SAH and vasospasm. ⋯ Monitoring of cerebral blood flow by laser Doppler showed a statistically similar decrease during injection in both groups. 7 days after SAH there was vasospasm of the middle and anterior cerebral arteries (51% reduction in MCA radius in SAH compared to saline-injected group, P<0.009, Student's t-test). In order to determine if SAH in this model was associated with neuronal injury, brains were examined for TUNEL and fluoro-jade-positive cells. 60% of SAH but not saline-injected mice exhibited TUNEL-positive cells in the cerebral cortex and 30% of the SAH but no saline-injected mice had fluoro-jade positive cells in the cortex, hippocampus and dentate gyrus. The model is simple to perform and may be useful for investigating the pathophysiology of SAH.
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In light of reports that the administration of fasudil, a Rho-kinase inhibitor, improved rats locomotor abilities following spinal cord injury, we hypothesized that combining fasudil with another type of therapy, such as stem cell transplantation, might further improve the level of locomotor recovery. Bone marrow stromal cells (BMSCs) are readily available for stem cell therapy. In the present study, we examined whether fasudil combined with BMSC transplantation would produce synergistic effects on recovery. ⋯ Double immunofluorescence studies showed no evidence of differentiation of grafted BMSCs into glial cells or neurons. The Rho-kinase inhibitor fasudil combined with BMSC transplantation resulted in better locomotor recovery than occurred in the untreated control group. However, the data failed to demonstrate significant synergism from combined therapy compared with the levels of recovery following single-agent treatment.
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The periaqueductal gray (PAG) plays an important role in morphine antinociception and tolerance. Co-localization of mu-opioid and NMDA receptors on dendrites in the PAG suggests that glutamate may modulate morphine antinociception. Moreover, the involvement of glutamate in spinally mediated tolerance to morphine suggests that glutamate receptors may contribute to PAG mediated tolerance. ⋯ That these antagonists enhance morphine antinociception indicates that endogenous glutamate counteracts the antinociceptive effect of morphine in the vPAG. However, this compensatory glutamate release does not contribute to tolerance to the antinociceptive effects of microinjecting morphine into the vPAG. Previous research showing that glutamate contributes to spinal mechanisms of tolerance indicate that different tolerance mechanisms are engaged in the vPAG and spinal cord.
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Validation of gait analysis has the potential to bridge the gap between data from animal pain models and clinical observations. The goal of these studies was to compare alterations in gait due to inflammation or nerve injury to traditional pain measurements in animals. Pharmacological experiments determined whether gait alterations were related to enhanced nociception, edema, or motor nerve dysfunction. ⋯ Gabapentin and duloxetine reversed mechanical hyperalgesia but did not normalize gait in any nerve injury model. Collectively, these data suggest that pain is the primary driver of abnormal gait in models of inflammatory but not nerve injury-related pain and suggests that, in the latter, disruption in gait is due to perturbation to the motor system. Gait may therefore constitute an alternative and potentially clinically relevant measure of pain due to inflammation.
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Previous studies from our group investigated the antinociceptive property of amyrin octanoate, a synthetic compound derivative from natural precursor alpha, beta-amyrin, against nociceptive response induced by acetic acid and formalin. Here, we investigated some of the mechanisms of action underlying the antinociceptive effects of amyrin octanoate. Amyrin octanoate given intraperitoneally (0.001-1 mg /kg) or intrathecally (10-1000 ng /site) caused dose-dependent and long-lasting inhibition of acetic acid-induced visceral nociception, with mean ID(50) values of 0.003 (0.001-0.005) mg/kg and 122.4 (60.8-246.6) ng/site, respectively. ⋯ The antinociception caused by amyrin octanoate in the acetic acid test was significantly attenuated by neonatal pretreatment of mice with capsaicin, but seems to involve mechanisms independent of G(i/o) protein, opioidergic, serotonergic, noradrenergic and cholinergic system, since it was not affected by pertussis toxin, naloxone, yohimbine, mecamylamine or atropine. In addition, amyrin octanoate reduced thermal and mechanical hyperalgesia induced by bradykinin and phorbol myristate acetate in rats, without affecting similar responses caused by prostaglandin E(2). Taken together, the present results shown that octanoate amyrin produces antinociceptive and antihyperalgesic effects, through an interaction with capsaicin-sensitive fibers and the inhibition of the PKC signaling pathway.