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Morphine inhibits acid-sensing ion channel currents in rat dorsal root ganglion neurons.
Brain Res. 2014 Mar 20; 1554:12-20.BR

Abstract

Extracellular acidosis is a common feature in pain-generating pathological conditions. Acid-sensing ion channels (ASICs), pH sensors, are distributed in peripheral sensory neurons and participate in nociception. Morphine exerts potent analgesic effects through the activation of opioid receptors for various pain conditions. A cross-talk between ASICs and opioid receptors in peripheral sensory neurons has not been shown so far. Here, we have found that morphine inhibits the activity of native ASICs in rat dorsal root ganglion (DRG) neurons. Morphine dose-dependently inhibited proton-gated currents mediated by ASICs in the presence of the TRPV1 inhibitor capsazepine. Morphine shifted the proton concentration-response curve downwards, with a decrease of 51.4±3.8% in the maximum current response but with no significant change in the pH0.5 value. Another μ-opioid receptor agonist DAMGO induced a similar decrease in ASIC currents compared with morphine. The morphine inhibition of ASIC currents was blocked by naloxone, a specific opioid receptor antagonist. Pretreatment of forskolin, an adenylyl cyclase activator, or the addition of cAMP reversed the inhibitory effect of morphine. Moreover, morphine altered acid-evoked excitability of rat DRG neurons and decreased the number of action potentials induced by acid stimuli. Finally, peripheral applied morphine relieved pain evoked by intraplantar of acetic acid in rats. Our results indicate that morphine can inhibit the activity of ASICs via μ-opioid receptor and cAMP dependent signal pathway. These observations demonstrate a cross-talk between ASICs and opioid receptors in peripheral sensory neurons, which was a novel analgesic mechanism of morphine.

Authors+Show Affiliations

Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China; Neurology Department, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, PR China.Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China.Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China.Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China.Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China.Neurology Department, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, PR China. Electronic address: lym9381@126.com.Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China. Electronic address: wangping_hu@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24491633

Citation

Cai, Qi, et al. "Morphine Inhibits Acid-sensing Ion Channel Currents in Rat Dorsal Root Ganglion Neurons." Brain Research, vol. 1554, 2014, pp. 12-20.
Cai Q, Qiu CY, Qiu F, et al. Morphine inhibits acid-sensing ion channel currents in rat dorsal root ganglion neurons. Brain Res. 2014;1554:12-20.
Cai, Q., Qiu, C. Y., Qiu, F., Liu, T. T., Qu, Z. W., Liu, Y. M., & Hu, W. P. (2014). Morphine inhibits acid-sensing ion channel currents in rat dorsal root ganglion neurons. Brain Research, 1554, 12-20. https://doi.org/10.1016/j.brainres.2014.01.042
Cai Q, et al. Morphine Inhibits Acid-sensing Ion Channel Currents in Rat Dorsal Root Ganglion Neurons. Brain Res. 2014 Mar 20;1554:12-20. PubMed PMID: 24491633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Morphine inhibits acid-sensing ion channel currents in rat dorsal root ganglion neurons. AU - Cai,Qi, AU - Qiu,Chun-Yu, AU - Qiu,Fang, AU - Liu,Ting-Ting, AU - Qu,Zu-Wei, AU - Liu,Yu-Min, AU - Hu,Wang-Ping, Y1 - 2014/02/01/ PY - 2013/07/18/received PY - 2014/01/18/revised PY - 2014/01/24/accepted PY - 2014/2/5/entrez PY - 2014/2/5/pubmed PY - 2014/12/15/medline KW - Acid-sensing ion channel KW - Dorsal root ganglion neuron KW - Electrophysiology KW - Morphine KW - Opioid receptor KW - Pain KW - Proton-gated current SP - 12 EP - 20 JF - Brain research JO - Brain Res VL - 1554 N2 - Extracellular acidosis is a common feature in pain-generating pathological conditions. Acid-sensing ion channels (ASICs), pH sensors, are distributed in peripheral sensory neurons and participate in nociception. Morphine exerts potent analgesic effects through the activation of opioid receptors for various pain conditions. A cross-talk between ASICs and opioid receptors in peripheral sensory neurons has not been shown so far. Here, we have found that morphine inhibits the activity of native ASICs in rat dorsal root ganglion (DRG) neurons. Morphine dose-dependently inhibited proton-gated currents mediated by ASICs in the presence of the TRPV1 inhibitor capsazepine. Morphine shifted the proton concentration-response curve downwards, with a decrease of 51.4±3.8% in the maximum current response but with no significant change in the pH0.5 value. Another μ-opioid receptor agonist DAMGO induced a similar decrease in ASIC currents compared with morphine. The morphine inhibition of ASIC currents was blocked by naloxone, a specific opioid receptor antagonist. Pretreatment of forskolin, an adenylyl cyclase activator, or the addition of cAMP reversed the inhibitory effect of morphine. Moreover, morphine altered acid-evoked excitability of rat DRG neurons and decreased the number of action potentials induced by acid stimuli. Finally, peripheral applied morphine relieved pain evoked by intraplantar of acetic acid in rats. Our results indicate that morphine can inhibit the activity of ASICs via μ-opioid receptor and cAMP dependent signal pathway. These observations demonstrate a cross-talk between ASICs and opioid receptors in peripheral sensory neurons, which was a novel analgesic mechanism of morphine. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/24491633/Morphine_inhibits_acid_sensing_ion_channel_currents_in_rat_dorsal_root_ganglion_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(14)00109-7 DB - PRIME DP - Unbound Medicine ER -