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Conditioned pain modulation in rodents can feature hyperalgesia or hypoalgesia depending on test stimulus intensity

Tansley, Shannon N.2; Macintyre, Leigh C.2; Diamond, Laura2; Sotocinal, Susana G.2; George, Nicole3; Meluban, Lee2; Austin, Jean-Sebastien2; Coderre, Terence J.3; Martin, Loren J.1,2,*; Mogil, Jeffrey S.2,3,*

doi: 10.1097/j.pain.0000000000001454
Research Paper: PDF Only

The counter-irritation phenomenon known as conditioned pain modulation (CPM), or diffuse noxious inhibitory control (DNIC) in animals, is of increasing interest due to its utility in predicting chronic pain and treatment response. It features considerable interindividual variability, with large subsets of pain patients and even normal volunteers exhibiting hyperalgesia rather than hypoalgesia during or immediately after receiving a conditioning stimulus. We observed that mice undergoing tonic inflammatory pain in the abdominal cavity (the conditioning stimulus) display hyperalgesia, not hypoalgesia, to noxious thermal stimulation (the test stimulus) applied to the hindpaw. In a series of parametric studies, we show that this hyperalgesia can be reliably observed using multiple conditioning stimuli (acetic acid, orofacial formalin), test stimuli (hind- and forepaw-withdrawal, tail-withdrawal, hot-plate and von Frey tests) and genotypes (CD-1, DBA/2 and C57BL/6 mice and Sprague Dawley rats). Whereas the magnitude of the hyperalgesia is dependent on the intensity of the conditioning stimulus, we find that the direction of effect is dependent on the effective test stimulus intensity, with lower-intensity stimuli leading to hyperalgesia and higher-intensity stimuli leading to hypoalgesia.

1Department of Psychology, University of Toronto Mississauga, Mississauga, ON L5L 1C6 CANADA

2Dept. of Psychology and Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3A 1B1 CANADA

3Dept. of Anesthesia and Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3G 1Y6 CANADA

Co-Corresponding authors: Jeffrey S. Mogil, Ph.D. McGill University Montreal, QC CANADA

© 2019 International Association for the Study of Pain
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