机构：[1]Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland[2]the Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology,Johns Hopkins University School of Medicine, Baltimore, Maryland[3]Department of Pharmacology and Molecular Sciences and the Center for Epigenetics,Johns Hopkins University School of Medicine, Baltimore, Maryland[4]the Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland[5]Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India[6]Department of Neurology, Tiantan Hospital, Capital Medical University, Beijing, China重点科室诊疗科室神经病学中心神经病学中心首都医科大学附属天坛医院[7]Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Wuhan, China其他科室麻醉科华中科技大学同济医学院附属同济医院[8]the Department of Orthopedics, Luhe Hospital, Capital Medical University, Beijing, China.
Background: Ongoing neuropathic pain is difficult to treat. The authors examined whether dermorphin [D-Arg2, Lys4] (1-4) amide, a peripherally acting mu-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 +/- 6 .3 vs. 322.1 +/- 5.0s, 10 mg/kg, n = 9, P = 0.009; mice: 437.8 +/- 59.4 vs. 351.3 +/- 95.9s, 2 mg/kg, n = 8, P = 0.047). Topical ganglionic application of dermorphin [D-Arg2, Lys4] (1-4) amide (5 mu M, 1 mu l, 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 (10mg/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 +/- 0.7g, 10 mg/kg, n = 8, P = 0.002) in nerve-injured rats, but the effect diminished after repeated administrations. Conclusions: Peripherally acting mu-opioids may attenuate ongoing pain-related behavior and its neurophysiologic correlates. Yet, repeated administrations cause antiallodynic tolerance. (ANESTHESIOLOGY 2018; 128:1220-36)
基金：
This study was supported by grants from the National Institutes
of Health (Bethesda, Maryland): R01NS70814 (Y.G.),
R01NS26363 (S.N.R.), and R21NS99879 (Y.G.). This work
was facilitated by the Pain Research Core funded by the
Blaustein Fund and the Neurosurgery Pain Research Institute
at Johns Hopkins University (Baltimore, Maryland).
第一作者机构：[1]Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland[5]Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India
共同第一作者：
通讯作者：
通讯机构：[1]Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland[*1]Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, 720 Rutland Avenue, Ross 350, Baltimore, Maryland 21205.
推荐引用方式(GB/T 7714)：
Tiwari Vinod,Anderson Michael,Yang Fei,et al.Peripherally Acting mu-Opioid Receptor Agonists Attenuate Ongoing Pain-associated Behavior and Spontaneous Neuronal Activity after Nerve Injury in Rats[J].ANESTHESIOLOGY.2018,128(6):1220-1236.doi:10.1097/ALN.0000000000002191.
APA：
Tiwari, Vinod,Anderson, Michael,Yang, Fei,Tiwari, Vineeta,Zheng, Qin...&Guan, Yun.(2018).Peripherally Acting mu-Opioid Receptor Agonists Attenuate Ongoing Pain-associated Behavior and Spontaneous Neuronal Activity after Nerve Injury in Rats.ANESTHESIOLOGY,128,(6)
MLA：
Tiwari, Vinod,et al."Peripherally Acting mu-Opioid Receptor Agonists Attenuate Ongoing Pain-associated Behavior and Spontaneous Neuronal Activity after Nerve Injury in Rats".ANESTHESIOLOGY 128..6(2018):1220-1236
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