Neuroscience letters
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Neuroscience letters · Aug 2010
Antihyperalgesic and antiallodynic effect of sirolimus in neuropathic pain and the role of cytokines in this effect.
Recent studies have revealed that T lymphocytes play a role in neuropathic pain following nerve injury in rats through releasing several cytokines. Sirolimus is an immunosuppressive antibiotic inhibiting T cell activation. This study aimed to determine the effect of sirolimus on hyperalgesia and allodynia and on serum and spinal cord TNF-alpha, IL-1beta and IL-6 levels in rat neuropathic pain. ⋯ However, TNF-alpha, but not IL-1beta or IL-6, protein level was increased in the spinal cord tissue as evaluated by Western blotting analysis. Treatment with sirolimus resulted in antihyperalgesic and antiallodynic effects and prevented the increased spinal cord TNF-alpha level. It seems that sirolimus could be a promising immunosuppressive agent in the treatment of neuropathic pain.
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Neuroscience letters · Aug 2010
Roles of adenosine receptor subtypes on the antinociceptive effect of sildenafil in rat spinal cord.
We recently found that the antinociceptive effects produced by intrathecal administration of sildenafil, a phosphodiesterase 5 inhibitor, were reversed by a nonspecific adenosine receptor antagonist, suggesting that adenosine receptors are involved in sildenafil-induced antinociception. Four adenosine receptor subtypes have been identified: A(1), A(2A), A(2B), and A(3). We examined the involvement of spinal adenosine receptor subtypes in the antinociceptive effects of intrathecal sildenafil. ⋯ Intrathecal CPT, CSC, alloxazine, and MRS 1220 all suppressed the antinociceptive effects of sildenafil during both phases of the formalin test. These results suggest that sildenafil is an effective treatment for acute pain and the facilitated pain state at the spinal level. Additionally, spinal adenosine A(1), A(2A), A(2B), and A(3) receptors may play a role in sildenafil-induced antinociception.
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Adaptation to a sustained stimulus is an important phenomenon in psychophysical experiments. When studying the response to an experimental task, the investigator has to account for the change in perceived stimulus intensity with repeated stimulus application and, if the stimulus is sustained, for the change in intensity during the presentation. An example of a sustained stimulus is the cold pressor task (CPT). ⋯ Using a mixed general linear model (effectively a polynomial regression model), we determined that pain ratings follow a crescendo-decrescendo pattern that can be described well using a quadratic model. We conclude that the time course of quantitative perception differs fundamentally from the time course of stimulus presentation. This may be important when looking for the physiological correlates of perception as opposed to the presence of a stimulus per se.
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Neuroscience letters · Aug 2010
Effects of repeated administered ghrelin on chronic constriction injury of the sciatic nerve in rats.
Chronic constriction injury (CCI) is a peripheral mononeuropathic pain model that is caused by an injury to the peripheral nervous system and refractory to available conventional treatment. Mechanisms involved in neuropathic pain are still unclear. Previous studies reveal that proinflammatory cytokines contribute to CCI-induced peripheral nerve pathology. ⋯ Ghrelin attenuated mechanical hyperalgesia, reduced spinal TNF-alpha and IL-1beta levels and enhanced sciatic nerve injury with correlated morphometric recovery. These results indicate that the protective effect by ghrelin in the spinal cord is mediated through the suppression of TNF-alpha and IL-1beta. Thus ghrelin may be a promising peptide in the management of neuropathic pain.
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Neuroscience letters · Aug 2010
Spinal TRPA1 ion channels contribute to cutaneous neurogenic inflammation in the rat.
In the spinal dorsal horn, TRPA1 ion channels on central terminals of peptidergic primary afferent nerve fibers regulate transmission to glutamatergic and GABAergic interneurons. Here we determine the cutaneous anti-inflammatory effect of a spinally administered TRPA1 channel antagonist to test the hypothesis that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation induced by sustained noxious stimulation. According to the hypothesis, spinal TRPA1 channels facilitate transmission of injury discharge to GABAergic interneurons that induce a dorsal root reflex, which results in increased release of proinflammatory compounds in the skin. ⋯ The capsaicin-induced blood flow increase was attenuated in a dose-related fashion by i.t. pretreatment with CHEM (3-10microg). Pretreatment with CHEM at a dose of 3mg/kg i.p. or 20microg i.pl. failed to attenuate the capsaicin-induced increase of blood flow. The results indicate that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation adjacent to the injury site, probably by facilitating a dorsal root reflex in peptidergic primary afferent nerve fibers.