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Hedonic drinking engages a supraspinal inhibition of thermal nociception in adult rats

Davies, Alexander J.a,b; Kim, Doyuna,c; Park, Jeongrakc; Lee, Jeong-Yunc; Vang, Huea; Pickering, Anthony E.d,e; Oh, Seog Baea,c,*

doi: 10.1097/j.pain.0000000000001482
Research Paper

The taste of sucrose is commonly used to provide pain relief in newborn humans and is innately analgesic to neonatal rodents. In adulthood, sucrose remains a strong motivator to feed, even in potentially hazardous circumstances (ie, threat of tissue damage). However, the neurobiological mechanisms of this endogenous reward–pain interaction are unclear. We have developed a simple model of sucrose drinking–induced analgesia in Sprague–Dawley rats (6-10 weeks old) and have undertaken a behavioral and pharmacological characterization using the Hargreaves' test of hind-paw thermal sensitivity. Our results reveal an acute, potent, and robust inhibitory effect of sucrose drinking on thermal nociceptive behaviour that unlike the phenomenon in neonates is independent of endogenous opioid signalling and does not seem to operate through classical descending inhibition of the spinal cord circuitry. Experience of sucrose drinking had a conditioning effect whereby the apparent expectancy of sucrose enabled water alone (in euvolemic animals) to elicit a short-lasting placebo-like analgesia. Sweet taste alone, however, was insufficient to elicit analgesia in adult rats intraorally perfused with sucrose. Instead, the sucrose analgesia phenomenon only appeared after conditioning by oral perfusion in chronically cannulated animals. This sucrose analgesia was completely prevented by systemic dosing of the endocannabinoid CB1 receptor antagonist rimonabant. These results indicate the presence of an endogenous supraspinal analgesic circuit that is recruited by the context of rewarding drinking and is dependent on endocannabinoid signalling. We propose that this hedonic sucrose-drinking model may be useful for further investigation of the supraspinal control of pain by appetite and reward.

Scientific: Hedonic drinking induces a potent thermal analgesia mediated supraspinally by endocannabinoid signalling at CB1 receptors. Lay: Drinking sweet beverages suppresses the behavioural response to heat pain due to the release of cannabis-like chemicals in the brain.

aDepartment of Neurobiology and Physiology, School of Dentistry, Dental Research Institute, Seoul National University, Seoul, Korea

bNuffield Department of Clinical Neuroscience, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom

cDepartment of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea

dSchool of Physiology, Pharmacology and Neuroscience, Medical Sciences Building, University of Bristol, Bristol, United Kingdom

eAnaesthesia, Pain and Critical Care Sciences, Translational Health Sciences, Bristol Medical School, Bristol Royal Infirmary, University of Bristol, Bristol, United Kingdom

Corresponding author. Address: Department of Neurobiology and Physiology, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Tel.: +82 (0)2 740 8656. E-mail address: (S.B. Oh).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

A.J. Davies and D. Kim contributed equally to this manuscript.

Received May 22, 2018

Received in revised form November 29, 2018

Accepted December 26, 2018

© 2019 International Association for the Study of Pain
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