PROLONGED ALLEVIATION OF TACTILE ALLODYNIA BY INTRAVENOUS LIDOCAINE IN NEUROPATHIC RATS

Background: Lidocaine may be useful in the treatment of neuropathic pa in states, The authors hypothesized that lidocaine would reduce tactil e allodynia observed in a rat nerve injury model. In an effort to dete rmine the site of drug action, effects after intravenous, intrathecal, and regional administration were compared. Methods: Rats underwent li gation of the left fifth and sixth lumbar spinal nerves. The 50% thres holds (g) for left hind paw withdrawal of awake rats to von Frey hairs were documented before, during, and after intravenous administration of lidocaine at programmed/documented pseudo-steady-state plasma conce ntrations, and correlated with measured plasma concentrations. Respons es to lidocaine application intrathecally and regionally to the injure d nerves were also recorded. Results: In rats with tactile allodynia, intravenous lidocaine yielded 66 +/- 11% of the maximal possible effec t on thresholds (100% = normal threshold), versus -1.3 +/- 2.7% for sa line infusion. Twenty-one days after lidocaine infusion, 30-40% of the maximal possible effect persisted. Threshold increases depended on pl asma concentration, rather than quantity of drug administered: rats re ceiving 15 mg/kg with higher plasma concentrations (1.2 +/- 0.1 mu g/m l) showed significant allodynia suppression throughout 7 days of follo w-up, whereas rats receiving 15 mg/kg at a slower rate with lower plas ma concentrations (0.6 +/- 0.1 mu g/ml) did not. The EC(50) for acute allodynia suppression was 0.75 mu g/ml. No such allodynia suppression was seen after intrathecal or regional administration of lidocaine des pite transient neural blockade. Conclusions: Intravenous, but not intr athecal or regionally applied, lidocaine produces dose-dependent suppr ession of allodynia associated with nerve injury. The effects far outl ast plasma concentrations of lidocaine. The mechanism of these prolong ed effects is unknown.