SUBANESTHETIC CONCENTRATIONS OF LIDOCAINE SELECTIVELY INHIBIT A NOCICEPTIVE RESPONSE IN THE ISOLATED RAT SPINAL-CORD

Systemically administered local anesthetics are known to provide analg esia in a variety of pain states; however, the site of action and the mechanism by which these effects are produced remain in question. In t he present study, the effects of low (subblocking for nerve conduction ) concentrations of lidocaine on a spinal cord nociceptive potential w ere studied. Spinal cords were removed from neonatal rats and maintain ed in vitro. Lumbar dorsal and ipsilateral ventral roots were attached to suction electrodes for stimulation and recording, respectively. Fo llowing a stabilization period (60-120 min) with control measurements, each preparation was exposed to a single concentration of lidocaine ( 30-60 min) then returned to control perfusate for recovery (60-120 min ). Data were digitized and integrals computed for both monosynaptic an d slow ventral root potentials (VRP). Low concentrations of lidocaine produced a selective reduction in the magnitude of the slow-VRP. At li docaine concentrations of 1-10 mu g/ml (3.6-36 mu M), the slow-VRP was reduced from 79% to 36% of control. Recovery to pre-exposure control levels was slow and sometimes not complete after 60-120 min in drug-fr ee perfusate. The monosynaptic component of the VRP was unaffected by lidocaine at any concentration, suggesting that the depression of the slow-VRP cannot be attributed to simple conduction block. The addition of naloxone 0.1 mu M to the perfusate had minimal effect on lidocaine -induced depression. Although resembling the selective effects of morp hine, the antinociceptive effects of lidocaine do not appear to be pri marily mediated through opiate receptors. Subblocking concentrations o f tetrodotoxin, a selective sodium-channel blocker, did not mimic the effects of lidocaine; However, a subblocking concentration of benzonat ate, an orally effective local anesthetic, did produce lidocaine-like selective effects on the slow-VRP. This study demonstrated that lidoca ine at clinically relevant concentrations can selectively depress a we ll-characterized nociceptive response in the isolated rat spinal cord. We propose that the site of action for systemic lidocaine analgesia i s, at least in part, at the level of the spinal cord.