Uncovering molecular elements of brain-body communication during development and treatment of neuropathic pain.
Integral to neuropathic pain is a reciprocal interaction between tumor necrosis factor-alpha (TNF) production and the alpha(2)-adrenergic receptor response, offering an attractive therapeutic target. The effects of varying levels of brain TNF on alpha(2)-adrenergic regulation of cyclic AMP (cAMP) production in the hippocampus and sciatic nerve were investigated during the development and amitriptyline treatment of chronic pain. Increased levels of TNF during the development of chronic pain transform alpha(2)-adrenergic inhibition of cAMP production in the brain to potentiation. While alpha(2)-adrenergic receptors regulate TNF production, they also affect descending noradrenergic pathways. Increases in levels of TNF in the brain deeply impact peripheral inflammation through regulating alpha(2)-adrenergic receptors, offering insight into brain-body interactions during neuropathic pain. Amitriptyline as an analgesic inhibits pain-induced increases in brain-associated TNF and transforms peripheral alpha(2)-adrenergic receptors. The dynamic equilibrium between TNF levels and alpha(2)-adrenergic functioning is uniquely altered during development and treatment of neuropathic pain. Proper manipulations of this interaction offer efficacious treatment of neuropathic pain.
Sud
Reeteka
R
Department of Pathology and Anatomical Sciences, School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 3435 Main Street, Buffalo, NY 14214, USA.
Ignatowski
Tracey A
TA
Lo
Crystal P K
CP
Spengler
Robert N
RN
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009409:Nerve Crush; D009437:Neuralgia / Q000378:metabolism* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018759:Adrenergic Uptake Inhibitors; D011942:Receptors, Adrenergic, alpha; D014409:Tumor Necrosis Factor-alpha; D000639:Amitriptyline; D000242:Cyclic AMP