Pain Input Impairs Recovery after Spinal Cord Injury: Treatment with Lidocaine

Abstract

More than 90% of spinal cord injuries are caused by traumatic accidents and are often associated with other tissue damage (polytrauma) that can provide a source of continued pain input during recovery. In a clinically relevant spinal cord contusion injury model, prior work has shown that noxious stimulation at an intensity that engages pain (C) fibers soon after injury augments secondary injury and impairs functional recovery. Noxious input increases the expression of pro-inflammatory cytokines (interleukin 1β and 18), cellular signals associated with cell death (caspase 3 and 8), and physiological signs of hemorrhage. Here, it is shown that reducing neural excitability after spinal cord injury (SCI) with the local anesthetic lidocaine (micro-injected by means of a lumbar puncture) blocks these adverse cellular effects. In contrast, treatment with an analgesic dose of morphine had no effect. Contused rats that received nociceptive stimulation soon after injury exhibited poor locomotor recovery, less weight gain, and greater tissue loss at the site of injury. Prophylactic application of lidocaine blocked the adverse effect of nociceptive stimulation on behavioral recovery and reduced tissue loss from secondary injury. The results suggest that quieting neural excitability using lidocaine can reduce the adverse effect of pain input (from polytrauma or surgery) after SCI.

Pain Input After Spinal Cord Injury (SCI) Undermines Long-Term Recovery and Engages Signal Pathways That Promote Cell Death

“…Recent work suggests that this process is related to the breakdown of the blood spinal cord barrier (BSCB). Supporting this, Turtle et al ( 2017 ) showed that the application of shock or capsaicin a day after rats received a contusion injury increased the infiltration of red blood cells into the injured tissue. Because hemoglobin is cytotoxic (Regan and Guo, 1998 ), this would fuel cell death and the expansion of injury.…”

“…This conclusion is based on work examining the effect of systemic morphine, given at a dose that completely blocks both spinal and brain-dependent responses to nociceptive stimulation (Hook et al, 2007 ). Morphine had no effect on shock-induced hemorrhage (Turtle et al, 2017 ). Nor did it attenuate the effect of shock treatment on long-term recovery (Hook et al, 2007 ).…”

“…More recently Turtle et al ( 2017 ) tested the effect of inhibiting cellular activity using the Na + channel blocker lidocaine. Contused rats were given lidocaine prior to shock treatment a day after injury.…”

Functional assessment of <em>CYP3A4</em> allelic variants on lidocaine metabolism in vitro

“…Lidocaine, which was the first sodium (Na + ) channel blocker, is still widely used in clinic as an amide-type local anesthetic agent now. 1 It inhibits nerve impulse transmission by blocking the fast voltage-gated Na + channels in the neuronal cell membrane thereby producing local anesthetic action. Lidocaine has good activity when it is applied to superficial body sites, penetrating mucous membranes to reduce the sensation of pain.…”

Stretching adversely modulates locomotor capacity following spinal cord injury via activation of nociceptive afferents.

“…Most recently Hook et al, found that administration of morphine, an opioid receptor agonist resulted in reduced sensory and motor recovery after SCI [306][307][308]. In the intact CNS the effect of transmission of impulses from nociceptive afferents is under the control of supraspinal systems originating in the midbrain (periaqueductal grey), and medulla (reticularis gigantocellularis (RG) and nucleus raphe magnus, (NRM)) [309].…”