Effect of nerve injury on noradrenaline augmentation of P2X3-mediated peripheral pain signaling: Role of injured fibres, strain and receptor subtype

Studies implicate ATP and noradrenaline in pain signaling. It has recently been observed that intraplantar injection of noradrenaline augments flinching behaviors mediated by the P2X3 receptor. Thus, it was of interest to study this interaction following injury. Paradoxically, pain behaviors produced by drug treatment were reduced following the partial sciatic ligation (PSL) model of nerve injury. Examination of the components of PSL: (1) inflammation (using the L5 neuritis model), and (2) injured sensory fields (using the spared nerve injury model), revealed that the injured sensory field, and not inflammation, resulted in reduced sensitivity as in the PSL model, while the uninjured lateral sensory field showed hypersensitivity. The adrenergic receptor subtype mediating the augmented alpha, beta-methylene-ATP induced behaviors was investigated using pharmacological agonists and antagonists, as well as inhibitors of downstream signaling; implicating the alpha 1-, and not alpha2-, adrenergic receptor in the Sprague-Dawley, Wistar, and Lewis strains of rat.