Subanesthetic concentrations of lidocaine selectively inhibit a nociceptive response in the isolated rat spinal cord

Abstract

Systemically administered local anesthetics are known to provide analgesia in a variety of pain states; however, the site of action and the mechanism by which these effects are produced remain in question. In the present study, the effects of low (subblocking for nerve conduction) concentrations of lidocaine on a spinal cord nociceptive potential were studied. Spinal cords were removed from neonatal rats and maintained in vitro. Lumbar dorsal and ipsilateral ventral roots were attached to suction electrodes for stimulation and recording, respectively. Following 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 and slow ventral root potentials (VRP). Low concentrations of lidocaine produced a selective reduction in the magnitude of the slow-VRP. At lidocaine concentrations of 1–10 μg/ml (3.6–36 μM), 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-free 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 μM to the perfusate had minimal effect on lidocaine-induced depression. Although resembling the selective effects of morphine, the antinociceptive effects of lidocaine do not appear to be primarily mediated through opiate receptors. Subblocking concentrations of tetrodotoxin, a selective sodium-channel blocker, did not mimic the effects of lidocaine. However, a subblocking concentration of benzonatate, an orally effective local anesthetic, did produce lidocaine-like selective effects on the slow-VRP. This study demonstrated that lidocaine at clinically relevant concentrations can selectively depress a well-characterized nociceptive response in the isolated rat spinal cord. We propose that the site of action for systemic lidocaine analgesia is, at least in part, at the level of the spinal cord.