Brain, behavior, and immunity
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Brain Behav. Immun. · Mar 2005
ReviewImmune-to-brain communication dynamically modulates pain: physiological and pathological consequences.
This review examines recently recognized roles of immunological processes in pain modulation and explores the potential implications of these immunologically derived phenomena for human chronic pain control. The focus is an examination of how activation of immune-like glial cells within the spinal cord can amplify pain by modulating the excitability of spinal neurons. Such glially driven enhancement of pain can be physiological, as occurs in response to peripheral infection or inflammation. ⋯ Here, immune- and trauma-induced alterations in peripheral nerve function lead to the release of substances within the spinal cord that trigger the activation of glia. Evidence is reviewed that such pathologically driven glial activation is associated with enhanced pain states of diverse etiologies and that such pain facilitation is driven by glial release of proinflammatory cytokines and other neuroexcitatory substances. This recently recognized role of spinal cord glia and glially derived proinflammatory cytokines as powerful modulators of pain is exciting as it may provide novel approaches for controlling human chronic pain states that are poorly controlled by currently available therapies.
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Brain Behav. Immun. · Mar 2005
Marginating pulmonary-NK activity and resistance to experimental tumor metastasis: suppression by surgery and the prophylactic use of a beta-adrenergic antagonist and a prostaglandin synthesis inhibitor.
Surgery is imperative for cancer treatment, but was suggested to suppress immunity and facilitate metastasis. Here we study the involvement of catecholamines and prostaglandins (PG) in such outcomes, and the role played by marginating-pulmonary (MP)-NK cells in controlling MADB106 metastasis. Non-operated and laparotomized F344 rats were injected postoperatively with a PG synthesis inhibitor (indomethacin, 4 mg/kg i.p.), a beta-blocker (nadolol, 0.6 mg/kg s.c.), both drugs, or vehicle. ⋯ Alterations in the numbers of NK cells were partly associated with alterations in total MP-NK activity, but not with circulating-NK activity. Last, administrating nai ve rats with physiologically relevant doses of a beta-adrenergic agonist (metaproterenol), and/or with PGE2, additively and independently of each other promoted MADB106 metastasis, simulating the effects of surgery. These findings point at potential prophylactic measures in cancer patients undergoing surgery, and suggest a role for MP-NK cells in resisting metastasis of apparently insensitive tumors.