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

The counterirritation phenomenon known as conditioned pain modulation, or diffuse noxious inhibitory control 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 pa...

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Published inPain (Amsterdam) Vol. 160; no. 4; pp. 784 - 792
Main Authors Tansley, Shannon N, Macintyre, Leigh C, Diamond, Laura, Sotocinal, Susana G, George, Nicole, Meluban, Lee, Austin, Jean-Sebastien, Coderre, Terence J, Martin, Loren J, Mogil, Jeffrey S
Format Journal Article
LanguageEnglish
Published United States 01.04.2019
Subjects
Acetic Acid - toxicity
Animals
Disease Models, Animal
Dose-Response Relationship, Drug
Facial Pain - complications
Formaldehyde - toxicity
Hyperalgesia - etiology
Hypesthesia - etiology
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Pain - complications
Pain - etiology
Pain Measurement
Peripheral Nerve Injuries - complications
Physical Stimulation - adverse effects
Psychophysics
Rats
Rats, Sprague-Dawley
Species Specificity
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Summary:The counterirritation phenomenon known as conditioned pain modulation, or diffuse noxious inhibitory control 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 and orofacial formalin), test stimuli (hindpaw 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). Although 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.
ISSN:0304-3959
1872-6623
DOI:10.1097/j.pain.0000000000001454