Newly Published
Pain Medicine  |   May 2020
Dorsal Root Ganglion Stimulation Alleviates Pain-related Behaviors in Rats with Nerve Injury and Osteoarthritis
Author Notes
  • From the Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin (G.Y., I.S., Z.Z., Q.H.H., B.P.); and the Department of Colon and Rectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan, China (Z.Z.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org)
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org)×
  • Submitted for publication December 9, 2019. Accepted for publication April 13, 2020.
    Submitted for publication December 9, 2019. Accepted for publication April 13, 2020.×
  • Correspondence: Address correspondence to Dr. Pan: Department of Anesthesiology, Medical College of Wisconsin, 8701 West Watertown Plank Road, Milwaukee, Wisconsin 53226. bpan@mcw.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Central and Peripheral Nervous Systems / Pain Medicine
Pain Medicine   |   May 2020
Dorsal Root Ganglion Stimulation Alleviates Pain-related Behaviors in Rats with Nerve Injury and Osteoarthritis
Anesthesiology Newly Published on May 18, 2020. doi:https://doi.org/10.1097/ALN.0000000000003348
Anesthesiology Newly Published on May 18, 2020. doi:https://doi.org/10.1097/ALN.0000000000003348
Abstract

Background:: Dorsal root ganglion field stimulation is an analgesic neuromodulation approach in use clinically, but its mechanism is unknown as there is no validated animal model for this purpose. The authors hypothesized that ganglion stimulation is effective in reducing pain-like behaviors in preclinical chronic pain models.

Methods: The authors provided ganglion stimulation or spinal cord stimulation to rats with traumatic neuropathy (tibial nerve injury), or osteoarthritis induced by intraarticular knee monosodium iodoacetate, or without injury (naïve). Analgesia was evaluated by testing a battery of pain-related reflexive, functional, and affective behaviors.

Results: In rats with nerve injury, multilevel L4 and L5 ganglion stimulation decreased hypersensitivity to noxious mechanical stimulation more (area under curve, −1,447 ± 423 min × % response; n = 12) than single level ganglion stimulation at L4 ([−960 ± 251 min × % response; n = 8; P = 0.012] vs. L4 and L5), and L5 ([−676 ± 295 min × % response; n = 8; P < 0.0001] vs. L4 and L5). Spontaneous pain-like behavior, evaluated by conditioned place preference, responded to single L4 (Pretest [−93 ± 65 s] vs. Test [87 ± 82 s]; P = 0.002; n = 9), L5 (Pretest [−57 ± 36 s] vs. Test [137 ± 73 s]; P = 0.001; n = 8), and multilevel L4 and L5 (Pretest: −81 ± 68 s vs. Test: 90 ± 76 s; P = 0.003; n = 8) ganglion stimulation. In rats with osteoarthritis, multilevel L3 and L4 ganglion stimulation reduced sensitivity to knee motion more (−156 ± 28 min × points; n = 8) than L3 ([−94 ± 19 min × points in knee bend test; n = 7; P = 0.002] vs. L3 and L4) or L4 ([−71 ± 22 min × points; n = 7; P < 0.0001] vs. L3 and L4). Conditioned place preference during osteoarthritis revealed analgesic effectiveness for ganglion stimulation when delivered at L3 (Pretest [−78 ± 77 s] vs. Test [68 ± 136 s]; P = 0.048; n = 9), L4 (Pretest [−96 ± 51 s] vs. Test [73 ± 111 s]; P = 0.004; n = 9), and L3 and L4 (Pretest [−69 ± 52 s; n = 7] vs. Test [55 ± 140 s]; P = 0.022; n = 7).

Conclusions: Dorsal root ganglion stimulation is effective in neuropathic and osteoarthritic preclinical rat pain models with peripheral pathologic origins, demonstrating effectiveness of ganglion stimulation in a placebo-free setting and justifying this model as a suitable platform for mechanistic studies.

Editor’s Perspective:

What We Already Know about This Topic:

  • Dorsal root ganglion stimulation is a new approach to neuromodulation for the purpose of achieving pain relief

  • Neuromodulation research has been slowed by the lack of well characterized animal models

What This Article Tells Us That Is New:

  • Using a rat model of osteoarthritis, stimulation of both the L3 and L4 dorsal root ganglia reduced nonreflexive knee motion scores and provided conditioned place preference more than sham stimulation

  • Sensitization from peripheral nerve injury responded to stimulation maximally when provided at two ganglia (L4 and L5) versus just one