scholarly journals Peripherally Acting μ-Opioid Receptor Agonists Attenuate Ongoing Pain-associated Behavior and Spontaneous Neuronal Activity after Nerve Injury in Rats

2018 ◽  
Vol 128 (6) ◽  
pp. 1220-1236 ◽  
Author(s):  
Vinod Tiwari ◽  
Michael Anderson ◽  
Fei Yang ◽  
Vineeta Tiwari ◽  
Qin Zheng ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Opioid Receptor ◽  
Dorsal Root ◽  
Dynamic Range ◽  
Place Preference ◽  
Wide Dynamic Range ◽  
Repeated Administrations ◽  
Ongoing Pain ◽  
Wide Dynamic Range Neurons

Abstract Background Ongoing neuropathic pain is difficult to treat. The authors examined whether dermorphin [D-Arg2, Lys4] (1–4) amide, a peripherally acting µ-opioid receptor agonist, attenuates ongoing pain-associated manifestations after nerve injury in rats and mice. Methods Using conditioned place preference assay, the authors tested whether animals show a preference to the environment associated with drug treatment. Wide-dynamic range and dorsal root ganglion neuronal activities were measured by electrophysiology recording and calcium imaging. Results Nerve-injured animals stayed longer in dermorphin [D-Arg2, Lys4] (1–4) amide–paired chamber after conditioning than during preconditioning (rats: 402.4 ± 61.3 vs. 322.1 ± 45.0 s, 10 mg/kg, n = 9, P = 0.009; mice: 437.8 ± 59.4 vs. 351.3 ± 95.9 s, 2 mg/kg, n = 8, P = 0.047). Topical ganglionic application of dermorphin [D-Arg2, Lys4] (1–4) amide (5 μM, 1 μl, n = 5) reduced the numbers of small-diameter dorsal root ganglion neurons that showed spontaneous activity (1.1 ± 0.4 vs. 1.5 ± 0.3, P = 0.044) and that were activated by test stimulation (15.5 ± 5.5 vs. 28.2 ± 8.2, P = 0.009) after injury. In neuropathic rats, dermorphin [D-Arg2, Lys4] (1–4) amide (10 mg/kg, n = 8) decreased spontaneous firing rates in wide-dynamic range neurons to 53.2 ± 46.6% of predrug level, and methylnaltrexone (5 mg/kg, n = 9) blocked dermorphin [D-Arg2, Lys4] (1–4) amide–induced place preference and inhibition of wide-dynamic range neurons. Dermorphin [D-Arg2, Lys4] (1–4) amide increased paw withdrawal threshold (17.5 ± 2.2 g) from baseline (3.5 ± 0.7 g, 10 mg/kg, n = 8, P = 0.002) in nerve-injured rats, but the effect diminished after repeated administrations. Conclusions Peripherally acting μ-opioids may attenuate ongoing pain-related behavior and its neurophysiologic correlates. Yet, repeated administrations cause antiallodynic tolerance.

scholarly journals Relationship of membrane properties, spike burst responses, laminar location, and functional class of dorsal horn neurons recorded in vitro

2016 ◽  
Vol 116 (3) ◽  
pp. 1137-1151 ◽  
Author(s):  
Patrick M. Dougherty ◽  
Jinghong Chen
Keyword(s):  
Dorsal Root ◽  
Dynamic Range ◽  
Functional Class ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
High Threshold ◽  
Wide Dynamic Range ◽  
Low Threshold ◽  
Wide Dynamic Range Neurons

The input-output and discharge properties of neurons are shaped by both passive and active electrophysiological membrane properties. Whole cell patch-clamp recordings in lamina I–III neurons in an isolated preparation of the whole spinal cord of juvenile rats with attached dorsal roots and dorsal root ganglia were used to further define which of these properties provides the most impactful classification strategy. A total of 95 neurons were recorded in segment L5 and were classified based on the responses to L4 dorsal root stimulation. The results showed that high-threshold and silent neurons had higher membrane resistance and more negative resting membrane potential than low-threshold or wide-dynamic-range neurons. Rheobase in low-threshold and wide-dynamic-range neurons was significantly lower than that of high-threshold or silent neurons. Four types of firing patterns were identified in response to depolarizing current injections. Low-threshold cells most frequently showed a phasic firing pattern characterized by a short initial burst of action potentials, single spiking or irregular firing bursts at the onset of a depolarizing pulse. High-threshold and wide-dynamic-range neurons were characterized by tonic firing with trains of spikes occurring at regular intervals throughout the current pulse. The majority of silent neurons displayed a delayed onset of firing in response to current injection. These results indicate that the passive membrane properties of spinal neurons are tuned to optimize the responses to particular subsets of afferent stimuli.

scholarly journals Dorsal Root Ganglion Stimulation Alleviates Pain-related Behaviors in Rats with Nerve Injury and Osteoarthritis

2020 ◽  
Vol 133 (2) ◽  
pp. 408-425 ◽  
Author(s):  
Guoliang Yu ◽  
Ian Segel ◽  
Zhiyong Zhang ◽  
Quinn H. Hogan ◽  
Bin Pan
Keyword(s):  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Conditioned Place Preference ◽  
Dorsal Root ◽  
Place Preference ◽  
Spontaneous Pain ◽  
Pain Models ◽  
Monosodium Iodoacetate ◽  
Traumatic Neuropathy ◽  
Noxious Mechanical Stimulation

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 What This Article Tells Us That Is New

Somatostatin Type 2 Receptor Antibody Enhances Mechanical Hyperalgesia in the Dorsal Root Ganglion Neurons after Sciatic Nerve-pinch Injury: Evidence of Behavioral Studies and Bax Protein Expression

2020 ◽  
Vol 18 (10) ◽  
pp. 791-797
Author(s):  
Qiong Xiang ◽  
Jing-Jing Li ◽  
Chun-Yan Li ◽  
Rong-Bo Tian ◽  
Xian-Hui Li
Keyword(s):  
Sciatic Nerve ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Dorsal Root ◽  
Underlying Mechanism ◽  
Dorsal Root Ganglion Neurons ◽  
Mechanical Hyperalgesia ◽  
Bax Protein ◽  
Ganglion Neurons

Background: Our previous study has indicated that somatostatin potently inhibits neuropathic pain through the activation of its type 2 receptor (SSTR2) in mouse dorsal root ganglion and spinal cord. However, the underlying mechanism of this activation has not been elucidated clearly Objective: The aim of this study is to perform the pharmacological studies on the basis of sciatic nerve-pinch mice model and explore the underlying mechanism involving SSTR2. Methods: On the basis of a sciatic nerve-pinch injury model, we aimed at comparing the painful behavior and dorsal root ganglion neurons neurochemical changes after the SSTR2 antibody (anti- SSTR2;5μl,1μg/ml) administration in the mouse. Results: After pinch nerve injury, we found that the mechanical hyperalgesia and severely painful behavior (autotomy) were detected after the application of SSTR2 antibody (anti-SSTR2; 5μl, 1μg/ml) on the pinch-injured nerve. The up-regulated phosphorylated ERK (p-ERK) expression and the apoptotic marker (i.e., Bax) were significantly decreased in DRGs after anti-SSTR2 treatment. Conclusion: The current data suggested that inhibitory changes in proteins from the apoptotic pathway in anti-SSTR2-treated groups might be taking place to overcome the protein deficits caused by SSTR2 antibody and supported the new therapeutic intervention with SSTR2 antagonist for neuronal degeneration following nerve injury.

scholarly journals Spinal integration of hot and cold nociceptive stimuli by wide-dynamic-range neurons in anesthetized adult rats

PAIN Reports ◽  
2021 ◽  
Vol 6 (4) ◽  
pp. e983
Author(s):  
Clémence Gieré ◽  
Meggane Melchior ◽  
André Dufour ◽  
Pierrick Poisbeau
Keyword(s):  
Dynamic Range ◽  
Wide Dynamic Range ◽  
Adult Rats ◽  
Wide Dynamic Range Neurons
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