Highlights
- •Field stimulation of the dorsal root ganglion is well tolerated in rats.
- •This treatment reverses allodynia and hyperalgesia that follow nerve injury.
- •Conditioned place preference shows that stimulation is rewarding during pain.
Abstract
Dorsal root ganglion (DRG) electrical stimulation (ganglionic field stimulation [GFS])
is effective in relieving clinical pain, but its mechanism is unknown. We therefore
developed a rat model for GFS to test analgesic effects in the context of neuropathic
pain. GFS was applied with a bipolar electrode at L4, using parameters replicating
clinical use (20 Hz, 150-μs pulse width, current at 80% of motor threshold). Neuropathic
pain was generated by tibial nerve injury (TNI). Pain behavior was monitored by determining
the threshold for withdrawal from punctate mechanical stimuli, by identifying hyperalgesic
responses to noxious mechanical stimuli, and by hypersensitivity to cold. The affective
dimension of pain was measured using conditioned place preference. We found that electrode
insertion caused no behavioral evidence of pain and produced no histological evidence
of DRG damage. GFS reversed TNI-induced hypersensitivity to cold and mechanical hyperalgesia
and allodynia. Allodynia remained diminished 15 minutes after GFS. Conditioned place
preference showed that GFS was not rewarding in uninjured control animals but was
rewarding in animals subjected to TNI, which reveals analgesic efficacy of GFS for
spontaneous pain. We conclude that GFS relieves neuropathic pain in rats. This model
may provide a platform for identifying mechanisms and novel applications of GFS.
Perspective
We show that electrical stimulation of the DRG in rats reverses neuropathic pain behavior
and provides a rewarding effect to animals with spontaneous neuropathic pain. This
confirms analgesic efficacy of DRG stimulation in an animal model, and provides a
platform for preclinical exploration.
Key words
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Article info
Publication history
Published online: September 26, 2016
Accepted:
September 13,
2016
Received in revised form:
August 23,
2016
Received:
June 16,
2016
Footnotes
Funding was provided by an unrestricted research grant from Spinal Modulation Inc. They had no role in the collection, analysis and interpretation of data. J. Kramer, a previous employee of Spinal Modulation Inc, participated in writing the report and approved of the decision to submit the article for publication.
Q.H. Hogan has received consultancy fees and research support from Spinal Modulation Inc. J.M. Kramer is an employee of St. Jude Medical Inc. The remaining authors have no conflicts of interest to declare.
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© 2016 by the American Pain Society
