Guoliang Yu1, Ian Segel, Zhiyong Zhang, Quinn H Hogan, Bin Pan. 1. From the Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin (G.Y., I.S., Z.Z., Q.H.H., B.P.) the Department of Colon and Rectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan, China (Z.Z.).
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.
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 ratpain 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.
Authors: Timothy R Deer; Robert M Levy; Jeffery Kramer; Lawrence Poree; Kasra Amirdelfan; Eric Grigsby; Peter Staats; Allen W Burton; Abram H Burgher; Jon Obray; James Scowcroft; Stan Golovac; Leonardo Kapural; Richard Paicius; Christopher Kim; Jason Pope; Thomas Yearwood; Sam Samuel; W Porter McRoberts; Hazmer Cassim; Mark Netherton; Nathan Miller; Michael Schaufele; Edward Tavel; Timothy Davis; Kristina Davis; Linda Johnson; Nagy Mekhail Journal: Pain Date: 2017-04 Impact factor: 7.926
Authors: Dongman Chao; Christina M Mecca; Guoliang Yu; Ian Segel; Michael S Gold; Quinn H Hogan; Bin Pan Journal: Pain Date: 2021-12-01 Impact factor: 6.961