Jun 3, 2008

Antinociception occurs with a reversal in alpha 2-adrenoceptor regulation of TNF production by peripheral monocytes/macrophages from pro- to anti-inflammatory

European Journal of Pharmacology
Reeteka SudTracey A Ignatowski


Tumor necrosis factor-alpha (TNF) plays a role in neuropathic pain. During neuropathic pain development in the chronic constriction injury model, elevated TNF levels in the brain occur in association with enhanced alpha 2-adrenoceptor inhibition of norepinephrine release. alpha 2-Adrenoceptors are also located on peripheral macrophage where they normally function as pro-inflammatory, since they increase the production of the cytokine TNF, a proximal mediator of inflammation. How the central increase in TNF affects peripheral alpha 2-adrenoceptor function was investigated. Male, Sprague-Dawley rats had four loose ligatures placed around the right sciatic nerve. Thermal hyperalgesia was determined by comparing hind paw withdrawal latencies between chronic constriction injury and sham-operated rats. Chronic constriction injury increased TNF immunoreactivity at the lesion and the hippocampus. Amitriptyline, an antidepressant that is used as an analgesic, was intraperitoneally administered (10 mg/kg) starting simultaneous with ligature placement (day-0) or at days-4 or -6 post-surgery. Amitriptyline treatment initiated at day-0 or day-4 post-ligature placement alleviated hyperalgesia. When initiated at day-0, amitriptyline prevented...Continue Reading

Mentioned in this Paper

Neuro-Oncological Ventral Antigen 2
Macrophages, Peritoneal
Biochemical Pathway
Salicylhydroxamic acid
Mononuclear Cells
Tumor Necrosis Factor-alpha
Structure of Sciatic Nerve

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