Involvement of Opioid Receptors and a2-Adrenoceptors in Inhibitory Pain Modulation Processes: A Double-Blind Placebo-Controlled Crossover Study

L. Vo, Sean Hood, P.D. Drummond

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    © 2016 American Pain Society
    In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only evokes local signs of central sensitization but also triggers broader ipsilateral inhibitory influences on pain akin to a lateralized form of conditioned pain modulation. Paradoxically, some of these inhibitory influences are augmented by a2-adrenoceptor blockade. To determine whether opioid peptides mediate inhibitory effects after HFS, the opioid receptor antagonist naltrexone was coadministered orally with the a2-adrenoceptor antagonist yohimbine in 16 healthy women in a double-blind placebo-controlled crossover study. In each session, mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, pain ratings to electrical stimulation of HFS-treated or control sites in the forearm were assessed during and after painful stimulation of each temple. Unlike yohimbine alone, the naltrexone with yohimbine combination blocked analgesia evoked by HFS in the ipsilateral forehead to blunt pressure, and opposed the ipsilateral inhibitory effect of pain in the temple on electrically-evoked pain at the HFS-treated site in the forearm. These findings imply involvement of opioid peptides in an ipsilateral analgesic response that complements the more generalized form of conditioned pain modulation. Opioid mediation of this ipsilateral analgesic response appears to override opposing a2-adrenoceptor effects. Perspective HFS not only evokes local signs of central sensitization but also triggers a broader ipsilateral antinociceptive mechanism mediated by opioid receptors. Dysfunction of this lateralized pain modulation process might contribute to painful unilateral disorders such as migraine or complex regional pain syndrome.
    Original languageEnglish
    Pages (from-to)1164-1173
    JournalJournal of Pain
    Volume17
    Issue number11
    Early online date4 Aug 2016
    DOIs
    Publication statusPublished - Nov 2016

    Fingerprint

    Opioid Receptors
    Cross-Over Studies
    Adrenergic Receptors
    Electric Stimulation
    Placebos
    Pain
    Forearm
    Yohimbine
    Central Nervous System Sensitization
    Naltrexone
    Forehead
    Opioid Peptides
    Analgesics
    Complex Regional Pain Syndromes
    Narcotic Antagonists
    Migraine Disorders
    Analgesia
    Opioid Analgesics
    Pressure

    Cite this

    @article{d54e0066d387441baabf383361009beb,
    title = "Involvement of Opioid Receptors and a2-Adrenoceptors in Inhibitory Pain Modulation Processes: A Double-Blind Placebo-Controlled Crossover Study",
    abstract = "{\circledC} 2016 American Pain SocietyIn healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only evokes local signs of central sensitization but also triggers broader ipsilateral inhibitory influences on pain akin to a lateralized form of conditioned pain modulation. Paradoxically, some of these inhibitory influences are augmented by a2-adrenoceptor blockade. To determine whether opioid peptides mediate inhibitory effects after HFS, the opioid receptor antagonist naltrexone was coadministered orally with the a2-adrenoceptor antagonist yohimbine in 16 healthy women in a double-blind placebo-controlled crossover study. In each session, mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, pain ratings to electrical stimulation of HFS-treated or control sites in the forearm were assessed during and after painful stimulation of each temple. Unlike yohimbine alone, the naltrexone with yohimbine combination blocked analgesia evoked by HFS in the ipsilateral forehead to blunt pressure, and opposed the ipsilateral inhibitory effect of pain in the temple on electrically-evoked pain at the HFS-treated site in the forearm. These findings imply involvement of opioid peptides in an ipsilateral analgesic response that complements the more generalized form of conditioned pain modulation. Opioid mediation of this ipsilateral analgesic response appears to override opposing a2-adrenoceptor effects. Perspective HFS not only evokes local signs of central sensitization but also triggers a broader ipsilateral antinociceptive mechanism mediated by opioid receptors. Dysfunction of this lateralized pain modulation process might contribute to painful unilateral disorders such as migraine or complex regional pain syndrome.",
    author = "L. Vo and Sean Hood and P.D. Drummond",
    year = "2016",
    month = "11",
    doi = "10.1016/j.jpain.2016.07.004",
    language = "English",
    volume = "17",
    pages = "1164--1173",
    journal = "The Journal of Pain",
    issn = "1526-5900",
    publisher = "Churchill Livingstone",
    number = "11",

    }

    Involvement of Opioid Receptors and a2-Adrenoceptors in Inhibitory Pain Modulation Processes: A Double-Blind Placebo-Controlled Crossover Study. / Vo, L.; Hood, Sean; Drummond, P.D.

    In: Journal of Pain, Vol. 17, No. 11, 11.2016, p. 1164-1173.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Involvement of Opioid Receptors and a2-Adrenoceptors in Inhibitory Pain Modulation Processes: A Double-Blind Placebo-Controlled Crossover Study

    AU - Vo, L.

    AU - Hood, Sean

    AU - Drummond, P.D.

    PY - 2016/11

    Y1 - 2016/11

    N2 - © 2016 American Pain SocietyIn healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only evokes local signs of central sensitization but also triggers broader ipsilateral inhibitory influences on pain akin to a lateralized form of conditioned pain modulation. Paradoxically, some of these inhibitory influences are augmented by a2-adrenoceptor blockade. To determine whether opioid peptides mediate inhibitory effects after HFS, the opioid receptor antagonist naltrexone was coadministered orally with the a2-adrenoceptor antagonist yohimbine in 16 healthy women in a double-blind placebo-controlled crossover study. In each session, mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, pain ratings to electrical stimulation of HFS-treated or control sites in the forearm were assessed during and after painful stimulation of each temple. Unlike yohimbine alone, the naltrexone with yohimbine combination blocked analgesia evoked by HFS in the ipsilateral forehead to blunt pressure, and opposed the ipsilateral inhibitory effect of pain in the temple on electrically-evoked pain at the HFS-treated site in the forearm. These findings imply involvement of opioid peptides in an ipsilateral analgesic response that complements the more generalized form of conditioned pain modulation. Opioid mediation of this ipsilateral analgesic response appears to override opposing a2-adrenoceptor effects. Perspective HFS not only evokes local signs of central sensitization but also triggers a broader ipsilateral antinociceptive mechanism mediated by opioid receptors. Dysfunction of this lateralized pain modulation process might contribute to painful unilateral disorders such as migraine or complex regional pain syndrome.

    AB - © 2016 American Pain SocietyIn healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only evokes local signs of central sensitization but also triggers broader ipsilateral inhibitory influences on pain akin to a lateralized form of conditioned pain modulation. Paradoxically, some of these inhibitory influences are augmented by a2-adrenoceptor blockade. To determine whether opioid peptides mediate inhibitory effects after HFS, the opioid receptor antagonist naltrexone was coadministered orally with the a2-adrenoceptor antagonist yohimbine in 16 healthy women in a double-blind placebo-controlled crossover study. In each session, mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, pain ratings to electrical stimulation of HFS-treated or control sites in the forearm were assessed during and after painful stimulation of each temple. Unlike yohimbine alone, the naltrexone with yohimbine combination blocked analgesia evoked by HFS in the ipsilateral forehead to blunt pressure, and opposed the ipsilateral inhibitory effect of pain in the temple on electrically-evoked pain at the HFS-treated site in the forearm. These findings imply involvement of opioid peptides in an ipsilateral analgesic response that complements the more generalized form of conditioned pain modulation. Opioid mediation of this ipsilateral analgesic response appears to override opposing a2-adrenoceptor effects. Perspective HFS not only evokes local signs of central sensitization but also triggers a broader ipsilateral antinociceptive mechanism mediated by opioid receptors. Dysfunction of this lateralized pain modulation process might contribute to painful unilateral disorders such as migraine or complex regional pain syndrome.

    U2 - 10.1016/j.jpain.2016.07.004

    DO - 10.1016/j.jpain.2016.07.004

    M3 - Article

    VL - 17

    SP - 1164

    EP - 1173

    JO - The Journal of Pain

    JF - The Journal of Pain

    SN - 1526-5900

    IS - 11

    ER -