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Repetitive C-fiber stimulation induces a state of facilitated processing of sensory information in the dorsal horn, while chronic nerve compression gives rise to a hyperalgesic state, characterized by spontaneous neuronal activity generated by voltage-sensitive sodium channels, as well as spinal facilitation.This study investigates the effects of systemic local anesthetic on thermal hyperalgesia evoked by chronic nerve compression and on the pain behavior responses to subcutaneous formalin.The effects of intravenous lidocaine were evaluated in rats with (1) the formalin test, a model of acute pain and centrally mediated delayed sensory sensitization, and (2) a model of chronic sciatic nerve compression leading to a neurogenic thermal hyperalgesia. Groups of rats (300 g) undergoing formalin testing were given intravenous lidocaine in doses of: 3 mg plus 25 μg/min infusion (yielding serum levels of 6.3 ± 1.0 μg/ml) or 1.5 mg plus 12.5 μg/min infusion (yielding serum levels of 3.6 ± 0.3 μg/ml) beginning 5 min before the subcutaneous injection of formalin in the left hind paw. In other studies, a group of six animals were rendered hyperalgesic in one hind limb by the placement of compressive ligatures about the left sciatic nerve (Bennett model) 3–5 days before these studies. These rats were treated with 0.6 mg intravenous lidocaine followed by an infusion of lidocaine at a rate of 5 μg/min (yielding serum levels of 1.0 ± 0.1 μg/ml).Lidocaine had no significant effect on the first phase of the formalin test or on thermal response latencies in normal limbs. However, at a high dose, lidocaine significantly reduced phase 2 flinching behavior and at a low dose, reversed the thermal hyperalgesia produced by sciatic nerve ligation during 30 min of infusion for a period of 3 h after the infusion was discontinued.Intravenous lidocaine acts by distinct mechanisms to diminish the hyperesthetic state induced by peripheral nerve injury and to reduce the degree of spinal sensitization induced by C-afferent fiber activation.