Effect of combined opioid receptor and α2-adrenoceptor blockade on anxiety and electrically evoked startle responses.
The R3 component of the electrically evoked blink reflex may form part of a startle reaction. Acoustic startle responses are augmented by yohimbine, an α2-adrenoceptor antagonist that blocks α2-autoreceptors, and are potentiated by opioid receptor blockade. To investigate these influences on electrically evoked startle responses, 16 mg yohimbine, with (16 participants) or without 50 mg naltrexone (23 participants), was administered in separate double-blind placebo-controlled cross-over experiments. In each experiment, R3 (a probable component of the startle response) was examined before and after high-frequency electrical stimulation of the forearm, a procedure that initiates inhibitory pain controls. Anxiety and somatic symptoms were greater after yohimbine than placebo, and were potentiated by naltrexone. Pain ratings for the electrically evoked startle stimuli decreased after high-frequency electrical stimulation in the placebo session but remained stable after drug administration. Yohimbine with naltrexone, but not yohimbine alone, also blocked an inhibitory effect of high-frequency electrical stimulation on electrically evoked sharp sensations and R3. Together, the findings suggest that adding naltrexone to yohimbine potentiated anxiety and blocked inhibitory influences of high-frequency electrical stimulation on electrically evoked sensations and startle responses. Thus, opioid peptides could reduce activity in nociceptive and startle-reflex pathways, or inhibit crosstalk between these pathways. Failure of this inhibitory opioid influence might be important in chronically painful conditions that are aggravated by startle stimuli.
Centre for Research on Chronic Pain and Inflammatory Diseases, Murdoch University, Perth, WA, Australia.
Lechi
L
Vo
Centre for Research on Chronic Pain and Inflammatory Diseases, Murdoch University, Perth, WA, Australia.
Peter D
PD
Drummond
D000293:Adolescent; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000627:therapeutic use*; D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D001767:Blinking / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D013216:Reflex, Startle / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology; D055815:Young Adult
D058669:Adrenergic alpha-2 Receptor Antagonists; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D018341:Receptors, Adrenergic, alpha-2; D011957:Receptors, Opioid; D015016:Yohimbine; D009271:Naltrexone
Startle; blink reflex; opioid receptor blockade; pain; α2-adrenoceptor blockade