• Vinod Tiwari, Michael Anderson, Fei Yang, Vineeta Tiwari, Qin Zheng, Shao-Qiu He, Tong Zhang, Bin Shu, Xueming Chen, Shaness A Grenald, Kimberly E Stephens, Zhiyong Chen, Xinzhong Dong, Srinivasa N Raja, and Yun Guan.
• From the Department of Anesthesiology and Critical Care Medicine (Vinod T., M.A., F.Y., Vineeta T., S.-Q.H., T.Z., B.S., S.A.G., Z.C., S.N.R., Y.G.) the Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology (M.A., Q.Z., X.D.) Department of Pharmacology and Molecular Sciences and the Center for Epigenetics (K.E.S.) the Howard Hughes Medical Institute (X.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India (Vinod T.) Department of Neurology, Tiantan Hospital, Capital Medical University, Beijing, China (T.Z.) Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Wuhan, China (B.S.) the Department of Orthopedics, Luhe Hospital, Capital Medical University, Beijing, China (X.C.).
• Anesthesiology. 2018 Jun 1; 128 (6): 122012361220-1236.

BackgroundOngoing 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.MethodsUsing 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.ResultsNerve-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.ConclusionsPeripherally acting μ-opioids may attenuate ongoing pain-related behavior and its neurophysiologic correlates. Yet, repeated administrations cause antiallodynic tolerance.

23 keywords...

hide…