title: Involvement of Opioid Receptors and α2-Adrenoceptors in Inhibitory Pain Modulation Processes: A Double-Blind Placebo-Controlled Crossover Study.
abstract: 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 α2-adrenoceptor blockade. To determine whether opioid peptides mediate inhibitory effects after HFS, the opioid receptor antagonist naltrexone was coadministered orally with the α2-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 α2-adrenoceptor effects.
  
  
  
  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.
authors: Centre for Research on Chronic Pain and Inflammatory Diseases, and School of Psychology and Exercise Science, Murdoch University, Perth, Western Australia, Australia.
authors: Lechi
authors: L
authors: Vo
authors: School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, Western Australia, Australia.
authors: Sean
authors: S
authors: Hood
authors: Centre for Research on Chronic Pain and Inflammatory Diseases, and School of Psychology and Exercise Science, Murdoch University, Perth, Western Australia, Australia. Electronic address: p.drummond@murdoch.edu.au.
authors: Peter D
authors: PD
authors: Drummond
mesh_terms: D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D059333:Central Nervous System Sensitization / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004333:Drug Administration Routes; D004558:Electric Stimulation / Q000009:adverse effects; D005260:Female; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D010147:Pain Measurement; D011601:Psychophysics; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D015016:Yohimbine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D009292:Narcotic Antagonists; D018341:Receptors, Adrenergic, alpha-2; D011957:Receptors, Opioid; D015016:Yohimbine; D009271:Naltrexone; D003000:Clonidine
keywords: High-frequency electrical stimulation; central sensitization; conditioned pain modulation; opioid receptors; α(2)-adrenoceptors