Continual systemic infusion of lidocaine provides analgesia in an animal model of neuropathic pain

Abstract

We examined whether continual constant-rate infusion of lidocaine would provide analgesia during the initial post-injury phase in the chronic constriction injury model of neuropathic pain. Male Sprague-Dawley rats were divided into control and ligated groups and infused with saline or lidocaine (0.15, 0.33, 0.67, and 1.3mg/kg/h) via subcutaneously implanted Alzet((R)) osmotic minipumps. Thermal withdrawal latencies were obtained prior (Day 0) and 3 days after loose sciatic ligation and pump implantation surgery. Ligated animals receiving lidocaine at 0.67 or 1.3mg/kg/h exhibited no change in withdrawal latency on Day 3 after surgery, indicating that lidocaine at these doses prevented the development of thermal hyperalgesia as a sign of neuropathic pain. In contrast, ligated animals treated with saline or lidocaine at 0.15 or 0.33mg/kg/h exhibited hyperalgesia on Day 3 after surgery, indicating that these lower doses of lidocaine failed to provide analgesia. Control animals treated with saline or any of the lidocaine doses exhibited no change in withdrawal latencies between Day 0 and Day 3. In a separate group of ligated animals, lidocaine infusion (0.67mg/kg/h) that was started 24h after sciatic ligation surgery reversed the already present thermal hyperalgesia. Average plasma lidocaine concentrations were 0.11, 0.36, and 0.45microg/ml for animals receiving 0.33, 0.67 and 1.3mg/kg/h of lidocaine, respectively. These results suggest that continual systemic infusion of lidocaine prevents or reverses the development of neuropathic pain following chronic constriction injury. These results add to the increasing body of evidence supporting the therapeutic value of preemptive and post-operative lidocaine administration for the relief of neuropathic pain.

Loose ligation of the sciatic nerve is associated with TrkB receptor-dependent decreases in KCC2 protein levels in the ipsilateral spinal dorsal horn

“…This finding on the failure of a single pre-emptive treatment was similar to our previous study in which we also found that only continual, rather than single, application of lidocaine was effective in abolishing pain behavior 7 days after loose ligation of the sciatic nerve (Smith et al, 2002).…”

Governing role of primary afferent drive in increased excitation of spinal nociceptive neurons in a model of sciatic neuropathy

“…Several studies have reported that systemic administration of lidocaine decreases ectopic activity recorded from injured peripheral sensory fibers (Chabal et al, 1989;Devor et al,1992;Omana-Zapata et al,1997a;Sotgiu et al, 1992) and reduces neuropathic pain (Brochu et al, 2006;Erichsen et al, 2003;Sinnott et al, 1999;Smith et al, 2002). Furthermore, systematic reviews of human studies using systemic administration of local anesthetic drugs support their use for neuropathic pain (Kalso et al, 1998) and, in addition, topical or local administration of antidepressants (Lynch et al, 2005;McCleane, 2000) and local anesthetics (Abram, 2000;Galer et al, 1999;Galer, 2002;Galer et al, 2002;Herrmann et al, 2005;Khaliq et al, 2007;Koltzenburg et al, 1994;Meier et al, 2003;Nystrom and Hagbarth, 1981;Roganovic and Mandic-Gajic, 2006;Rowbotham et al, 1996;Varrassi et al, 2006;Vranken et al, 2002) have been demonstrated to be effective in treating neuropathic pain in controlled clinical trials.…”

Lidocaine treatment during synapse reformation periods permanently inhibits NGF-induced excitation in an identified reconstructed synapse of Lymnaea stagnalis

“…)-channel blockade, probably due to their pharmacological properties. Although the underlying mechanisms of this persistent analgesic effect are largely unknown, several hypotheses have been proposed: interrupting nociceptor activity with local anesthetics not only leads to reversible sensitization of spinal-cord neurons but might also induce plastic changes in neurons depending on the timing and period of exposure [5][6][7]. Identifying the mechanisms of action of local anesthetics to relieve chronic pain might lead to the development of a new strategy to treat neuropathic pain.…”