Dorsal Root Ganglionic Field Stimulation Relieves Spontaneous and Induced Neuropathic Pain in Rats.
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.



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.
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Bin
B
Pan
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Hongwei
H
Yu
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Gregory J
GJ
Fischer
St. Jude Medical, Inc, Sunnyvale, California.
Jeffery M
JM
Kramer
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin; Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin. Electronic address: qhogan@mcw.edu.
Quinn H
QH
Hogan
D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D001703:Biophysics; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003216:Conditioning, Operant / Q000502:physiology; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods*; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000628:therapy; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009437:Neuralgia / Q000628:therapy*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013696:Temperature; D013979:Tibial Nerve / Q000503:physiopathology; D013997:Time Factors; D058127:Transcription Factor 3 / Q000378:metabolism
D051700:Activating Transcription Factor 3; C100745:Aif1 protein, rat; C497108:Atf3 protein, rat; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D058127:Transcription Factor 3
Dorsal root ganglion; analgesic stimulation; conditioned place preference; neuromodulation; neuropathic pain