Brain research
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The aim of the present study was to explore variation in skin blood flow and temperature following experimental muscle pain. In 14 male human subjects, 2 ml and 4.8 ml of hypertonic (5.8%) saline were injected into the left tibialis anterior (TA) muscle to induce muscle pain. The subjects rated the pain intensity on a 10 cm visual analogue scale (VAS). ⋯ These results suggested that the vasodilation in different skin areas following intramuscular injection of hypertonic saline was dose-dependent. Injection of 4.8 ml hypertonic saline after local intramuscular anesthesia (2% lidocaine) did not evoke any significant changes in skin blood flow or skin temperature in any of the four observation areas. This suggested that both homotopic and heterotopic vascular reactions triggered by hypertonic saline stimulation of thin muscle afferent fibers were a neurogenically associated reaction.
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This study was designed to investigate the effect of acute intrathecal (i.t.) injection of amitriptyline (AMI) on the antinociceptive effect of morphine in rats treated with pertussis toxin (PTX). Male Wistar rats were implanted with an i.t. catheter for drug injection and some were implanted with an additional microdialysis probe used for CSF dialysate collection and measurement of excitatory amino acids (EAAs). The expression of glutamate transporters (GTs) in the spinal cord dorsal horn was also measured. ⋯ In contrast, AMI (15 microg, i.t.) pretreatment followed 30 min later by morphine (10 microg, i.t.) injection inhibited the increase in EAA concentrations and reversed the downregulation of all three GTs. Our results show that AMI preserves the antinociceptive effect of morphine in PTX-treated rats. The mechanisms involve suppression of the increase in EAA concentrations in spinal CSF dialysates and reversion of GT expression in PTX-treated rats.
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Neuritic dystrophy with amyloid burden and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease. Genetic disruption of CD40 or CD40L alleviates amyloid burden, astrocytosis, and microgliosis in transgenic animal models of Alzheimer's disease. It has been reported that phosphorylated tau-positive dystrophic neurites are observed in transgenic mice over-expressing human mutant beta-amyloid precursor protein (Tg2576). ⋯ Further, we show that CD40L or CD40 deficiency reduces the mean ratio of dystrophic neurite area to congophilic plaque area and the level of expression of cdk5 and p35/p25 in mice. In addition, we show that in a human neuroblastoma cell line treated with CD40L, cdk5 and p35/p25 are increased. Together, our data suggest that CD40-CD40L interaction has an effect on tau phosphorylation independent of beta-amyloid pathology, and that this effect may occur through a decrease of cdk5 and p35/p25.
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It is well known that prior experience to the elevated plus-maze increases the avoidance of rodents to the open arms and impairs the anxiolytic-like effect of benzodiazepines evaluated during a subsequent exposure to the maze, a phenomenon known as "one-trial tolerance". Centrally injected benzodiazepine drugs attenuate anxiety in some limbic structures, such as hypothalamus, amygdala and the midbrain periaqueductal gray (PAG). This study investigated the effects of intra-PAG infusions of midazolam (MDZ) in maze-naïve and maze-experienced mice. ⋯ The antiaversive effects of MDZ were completely blocked by prior injection of flumazenil which in turn did not alter any other behavioral measure. In maze-experienced mice, intra-PAG infusion of MDZ did not modify any behavioral measure. Taken together, present results corroborate previous studies demonstrating that GABA/benzodiazepine receptor complex located within the PAG plays a role on anxiety modulation in maze-naïve mice as well as indicate its involvement in the OTT phenomenon.
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Elevation of extracellular glutamate contributes to cell death and functional impairments generated by spinal cord injury (SCI), in part through the activation of the neurotoxic cytokine interleukin-1beta (IL-1beta). This study examines the participation of IL-1beta and its regulation by the endogenous interleukin-1 receptor antagonist (IL-1ra) in glutamate toxicity following SCI. Glutamate, glutamatergic agonists and SCI had similar effects on levels of IL-1beta and IL-1ra. ⋯ Infusing IL-beta into the spinal cord impaired locomotion, and infusing IL-1ra improved recovery from glutamate-induced motor impairments. We hypothesize that elevating IL-1ra opposes the damage caused by IL-1beta in SCI by reducing IL-1beta levels as well as by blocking binding of IL-1beta to its receptor. Our results demonstrate that IL-1beta contributes to glutamate damage following SCI; blocking IL-1beta may usefully counteract glutamate toxicity.