Brain research
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It has been suggested that long-term potentiation (LTP) of dorsal horn neurons is a phenomenon that contributes to the development of chronic neuropathic pain. Spinal cord stimulation (SCS) may be an effective tool in alleviating such pain. The aim of this electrophysiological study in rats was to examine if SCS suppresses LTP of dorsal horn wide dynamic range (WDR) neurons. ⋯ Here we report that SCS gradually reduced this increased C-fiber response back to the baseline level. However, A-fiber responses were neither potentiated by the conditioning stimulus used nor were they affected by SCS. These data suggest that SCS affects the C-fiber component of dorsal horn central sensitization which is noteworthy since SCS, based on previous studies, is believed to primarily influence A-fiber functions.
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Ischemic cerebrovascular disease (stroke) is one of the leading causes of death and long-time disability. Ischemia/reperfusion to any organ triggers a complex series of biochemical events, which affect the structure and function of every organelle and subcellular system of the affected cells. The purpose of this study was to investigate the therapeutic efficacy of N-acetyl cysteine (NAC), a precursor of glutathione and a potent antioxidant, to attenuate ischemia/reperfusion injury to brain tissue caused by a focal cerebral ischemia model in rats. ⋯ NAC treatment also blocked the ischemia/reperfusion-induced expression of tumor necrosis factor and inducible nitric oxide synthase. The data suggest that pre-administration of NAC attenuates cerebral ischemia and reperfusion injury in this brain ischemia model. This protective effect may be as a result of suppression of TNF-alpha and iNOS.
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We have previously shown that colon irritation (CI) in neonates results in chronic visceral hypersensitivity in adult rats, associated with central neuronal sensitization in the absence of identifiable peripheral pathology. The purpose of this study is to assess the relative contribution of peripheral mechanisms to chronic visceral hypersensitivity by examining the changes in responses of primary afferents at thoracolumbar (TL) and lumbosacral (LS) spinal segments to graded colorectal distension (CRD). Afferent discharges were recorded at the cut distal ends of spinal dorsal roots (DRs) in adult control and CI rats. ⋯ In summary, the results show that chronic visceral hypersensitivity is associated with peripheral sensitization, as well as central sensitization. TL visceral afferents projecting seem to be more involved in the processing of sensitized nociceptive input from the colon than acute nociceptive input. However, LS afferents seem to be equally important in both sensitized and acute pain states.
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Peripheral nerve injury in rodents results in hypersensitivity to mechanical and thermal stimuli accompanied by reduced antinociceptive efficacy of opioids and, in some models, sensitivity to sympathetic blockade. alpha2-Adrenergic receptor agonists increase in potency and efficacy after nerve injury in rodents and effectively relieve neuropathic pain in humans who do not get pain relief from opioids. However, the underlying mechanisms are unclear. It has been well known that the major noradrenergic innervation of the spinal dorsal horn originates from the locus coeruleus nucleus (LC) in the brainstem. ⋯ Interestingly, in the lower lumbar and upper sacral spinal dorsal horn, numerous TH-IR neurons were observed in the superficial dorsal horn (primarily lamina I). CCI of the sciatic nerve did not change the number of these TH-IR cells. These findings suggest that augmented descending inhibitory noradrenergic innervation to the dorsal horn could be one of the mechanisms underlying the increased effectiveness in the anti-allodynic effect elicited by alpha2-adrenergic receptor agonists.
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Unilateral T13 hemisection of the rat spinal cord produces a model of chronic spinal cord injury (SCI) that is characterized by bilateral hyperexcitability of lumbar dorsal horn neurons, and behavioral signs of central pain. While we have demonstrated that responsiveness of multireceptive (MR) dorsal horn neurons is dramatically increased at 28 days after injury, the effects of acute hemisection are unknown and predicted to be different than observed chronically. In the present study, the consequences of T13 hemisection are examined acutely at 45 min in MR neurons both ipsilateral and contralateral to the site of injury, and compared to the same class of cells at 28 days after injury (n=20 cells total per group: 2-3 cells/side of the cord from n=5 animals). ⋯ In animals 28 days after hemisection, spontaneous activity of MR neurons was comparable to intact levels ipsilaterally, and cells exhibited hyperexcitability to evoked stimuli bilaterally. Expansion of cutaneous receptive fields was observed only in hindpaws ipsilateral to the lesion, acutely. These results demonstrate dynamic plasticity in properties of dorsal horn somatosensory neurons after SCI.