Pain
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Spinal cord fMRI offers an excellent opportunity to quantify nociception using neuronal activation induced by painful stimuli. Measurement of the magnitude of stimulation-induced activation, and its suppression with analgesics can provide objective measures of pain and efficacy of analgesics. This study investigates the feasibility of using spinal cord fMRI in anesthetized rats as a pain assay to test the analgesic effect of locally and systemically administered lidocaine. ⋯ Local administration of lidocaine was shown to ablate all stimulation-induced fMRI signals by the total blockage of peripheral nerve transmission, while the analgesic effect of systemically administered lidocaine was robustly detected after intravenous infusion of approximately 3mg/kg, which is similar to clinical dosage for human. This study establishes spinal cord fMRI as a viable assay for analgesics. With respect to the mode of action of lidocaine, this study suggests that systemic lidocaine, which is clinically used for the treatment of neuropathic pain, and believed to only block the peripheral nerve transmission of abnormal neural activity (ectopic discharge) originating from the damaged peripheral nerves, also blocks the peripheral nerve transmission of normal neural activity induced by transcutaneous noxious electrical stimulation.
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Chronic alcohol consumption produces a painful peripheral neuropathy for which there is no reliable successful therapy, which is mainly due to lack of understanding of its pathobiology. Alcoholic neuropathy is characterized by spontaneous burning pain, hyperalgesia (an exaggerated pain in response to painful stimuli) and allodynia (a pain evoked by normally innocuous stimuli). Chronic alcohol intake is known to decrease the nociceptive threshold with increased oxidative-nitrosative stress and release of proinflammatory cytokines coupled with activation of protein kinase C. ⋯ TNF-alpha and IL-1beta levels were also significantly increased in both serum and sciatic nerve of ethanol-treated rats. Treatment with alpha-tocopherol and tocotrienol for 10 weeks significantly improved all the above-stated functional and biochemical deficits in a dose-dependent manner with more potent effects observed with tocotrienol. The study demonstrates the effectiveness of tocotrienol in attenuation of alcoholic neuropathy.