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

Shai Lee Yatziv, Marshall Devor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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-mL 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.

Original languageEnglish
Pages (from-to)2105-2114
Number of pages10
JournalPain
Volume160
Issue number9
DOIs
StatePublished - 1 Sep 2019

Bibliographical note

Publisher Copyright:
© 2019 International Association for the Study of Pain.

Keywords

  • Dorsal root ganglion
  • Ectopic discharge
  • Neuropathic pain
  • Safety factor
  • Selective block

Fingerprint

Dive into the research topics of 'Suppression of neuropathic pain by selective silencing of dorsal root ganglion ectopia using nonblocking concentrations of lidocaine'. Together they form a unique fingerprint.

Cite this