Upregulation of IL-6 and its signaling molecules after nerve injury: the concept of Yin Yang for reinnervation and induction of neuropathic pain
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| Year of publication | 2012 |
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| Description | In Asian philosophy, the concept of Yin Yang is used to describe how seemingly contrary forces are interconnected and interdependent in the natural world, and how they give rise to each other in turn. Opposites thus only exist in relation to each other. Wallerian degeneration is a cascade of stereotype cellular events and molecular alterations distal to injury of nerve fibers including upregulation of inflammatory mediators like cytokines. These events may prepare conditions for both regeneration of damaged axons and induction of neuropathic pain. The goal of our present experiments was to study IL-6 and its signaling molecules in the model of peripheral nerve injury in relation to regrowing axons and induction of neuropathic pain. Unilateral chronic constriction injury (CCI) of the sciatic nerve was performed aseptically in sixty four rats. Neuropathic pain induction was tested by withdrawal threshold of mechanoallodynia and thermal hyperalgesia. Expression of IL-6, IL-6R, gp130, STAT-3 and SOCS3 were investigated bilaterally in the sciatic nerve as well as in both lumbar (L4-5) and cervical (C7-8) dorsal root ganglia (DRG) following CCI for 1, 3, 7 and 14 days. Regrowing axons were detected simultaneously by GAP-43 immunostaining. The results of immunofluorescence staining revealed that activated Schwann cells distal to nerve constriction and satellite glial cells of DRG are robust source for IL-6 and molecules for its signal transduction and regulation. Activated Schwann cells that displayed IL-6 protein and its signal molecules were found in close contact with growing axons as well as in contralateral homonymous nerve. Activated satellite glial cells producing inflammatory mediators are involved in ectopic activation of the primary sensory neurons or their neuroprotection. Both beneficial and detrimental effects of IL6 distal to nerve injury and in DRG have to be considered in a strategy of axon promotion on one side and suppression of the initial stages of neuropathic pain on other side. Some recent knowledge on this topic is stressed. |
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