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-α (TNF) production and the α2-adrenergic receptor response, offering an attractive therapeutic target. The effects of varying levels of brain TNF on α2-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 α2-adrenergic inhibition of cAMP production in the brain to potentiation. While α2-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 α2-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 α2-adrenergic receptors. The dynamic equilibrium between TNF levels and α2-adrenergic functioning is uniquely altered during development and treatment of neuropathic pain. Proper manipulations of this interaction offer efficacious treatment of neuropathic pain.