Neuropathic pain - page 7 Scientific Publications

Latest publication 03/29/2018

Peripherally Acting _-Opioid Receptor Agonists Attenuate Ongoing Pain-associated

Methods: Using conditioned place preference assay, the authors tested whether animals show a preference to the environment associated with drug...

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    [title] => Peripherally Acting _-Opioid Receptor Agonists Attenuate Ongoing Pain-associated
    [paragraph] => Peripherally Acting _-Opioid Receptor Agonists Attenuate Ongoing Pain-associated Behavior and Spontaneous Neuronal Activity after Nerve Injury in Rats 
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Authors
V Tiwari, M Anderson, F Yang, V Tiwari, Q Zheng, et al.

 Lab
Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA
Journal
Anesthesiology
Abstract
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] (1Ð4) amideÐpaired 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] (1Ð4) amide (5 _M, 1 _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] (1Ð4) 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] (1Ð4) amideÐinduced place preference and inhibition of wide-dynamic range neurons. Dermorphin [D-Arg2, Lys4] (1Ð4) 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 _-opioids may attenuate ongoing pain-related behavior and its neurophysiologic correlates. Yet, repeated administrations cause antiallodynic tolerance.
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