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Suppression of neuropathic pain by selective silencing of dorsal root ganglion ectopia using nonblocking concentrations of lidocaine

Yatziv, Shai-Leea; Devor, Marshalla,b,*

doi: 10.1097/j.pain.0000000000001602
Research Paper
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Neuropathic pain is frequently driven by ectopic impulse discharge (ectopia) generated in injured peripheral afferent neurons. Observations in the spinal nerve ligation (SNL) model in rats suggest that cell bodies in the dorsal root ganglion (DRG) contribute 3 times more to the ectopic barrage than the site of nerve injury (neuroma). The DRG is therefore a prime interventional target for pain control. Since DRG ectopia is selectively suppressed with lidocaine at concentrations too low to block axonal impulse propagation, we asked whether targeted delivery of dilute lidocaine to the L5 DRG can relieve L5 SNL-induced tactile allodynia without blocking normal sensation or motor function. Results showed that intraforaminal injection of 10-µL bolus doses of 0.2% lidocaine suppressed allodynia transiently, while sustained infusion over 2 weeks using osmotic minipumps suppressed it for the duration of the infusion. Bolus injections of morphine or fentanyl were ineffective. Lidocaine applied to the cut spinal nerve end or the L4 DRG did not affect allodynia, suggesting that discharge originating in the neuroma and in neighboring “uninjured” afferents makes at best a minor contribution. Spike electrogenesis in the DRG is apparently the primary driver of tactile allodynia in the SNL model of neuropathic pain, and it can be controlled selectively by superfusing the relevant DRG(s) with nonblocking concentrations of lidocaine. This approach has potential clinical application in conditions such as postherpetic neuralgia and phantom limb pain in which one or only a few identifiable ganglia are implicated as pain drivers.

Sustained intraforaminal delivery of dilute lidocaine to the L5 dorsal root ganglion suppresses neuropathic tactile allodynia for an extended period without causing sensory or motor block.

aDepartment of Cell and Developmental Biology, Silberman Institute of Life Sciences and the

bCenter for Research on Pain The Hebrew University of Jerusalem, Jerusalem, Israel

Corresponding author. Address: Department of Cell and Developmental Biology, Silberman Institute of Life Sciences, the Hebrew University of Jerusalem, Jerusalem 9190401, Israel. Tel.: +972 2 658-5085. E-mail address: marshlu@mail.huji.ac.il (M. Devor).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Received February 11, 2019

Received in revised form April 10, 2019

Accepted April 26, 2019

Online date: April 29, 2019

© 2019 International Association for the Study of Pain
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