Highlights
- •Limb pain evokes an ipsilateral form of conditioned pain modulation.
- •Opioid peptides mediate this response in the painful limb and ipsilateral forehead.
- •These inhibitory opioid influences override opposing α2-adrenoceptor effects.
- •Failure of this ipsilateral opioid response may aggravate chronic limb or head pain.
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.
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.
Key words
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Article info
Publication history
Published online: August 04, 2016
Accepted:
July 27,
2016
Received in revised form:
June 27,
2016
Received:
March 21,
2016
Footnotes
The study was supported by the National Health and Medical Research Council of Australia (grant number 437205). The funding body had no role in the design, conduct, analysis or reporting of the study.
The authors have no conflicts of interest to declare.
Supplementary data accompanying this article are available online at www.jpain.org and www.sciencedirect.com.
Identification
Copyright
© 2016 by the American Pain Society
