Perioperative administration of the alpha2-adrenoceptor agonist clonidine at the site of nerve injury reduces the development of mechanical hypersensitivity and modulates local cytokine expression.

摘要: The development of chronic pain after surgery is not rare. Nerve injury from complete or partial nerve section during leads to macrophage recruitment and release pro-inflammatory cytokines, leading in turn sensitization. Macrophages also express alpha2-adrenoceptors, we previously demonstrated a prolonged reduction hypersensitivity following peri-neural injection the alpha2-adrenoceptor agonist, clonidine, rats with injury. current study tested whether clonidine at time could prevent hypersensitivity. Rats underwent ligation one sciatic nerve, saline, combination alpha2A-adrenceptor-preferring antagonist, BRL44408, were administered before wound closure and, some animals, 24 48 h later. single reduced for only 5 h, whereas repeated three days 28 days. Peri-neural increase tissue content proinflammatory cytokines IL-1beta particularly TNFalpha DRG spinal cord while increasing concentrations anti-inflammatory cytokine TGF-beta1. Clonidine's effects on behavior blocked by BRL44408. We conclude that administration site reduces degree part altering balance pro- through activation alpha2A-adrenoceptors. These results support testing as an adjuvant continuous peripheral blocks settings known major injury, such limb amputation, might pain.