Pain, 32 (1988) 77-88 Elsevier PAI 01152 77 Basic Section A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia K. Hargreaves, R. Dubner, F. Brown, C. Flores and J. Joris 1 Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892 (U.S.A.) (Received 13 April 1987, revised received 13 August 1987, accepted 17 August 1987) Summary A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold. Key words: Cutaneous hyperalgesia; Thermal nociception Introduction Despite the advantages of using thermal stimu- lation [5], no behavioral method exists for quanti- fying thermal nociception in animal models of hyperalgesia. Determination of acute nociceptive thermal thresholds in animals has primarily relied upon the tail flick and hot plate methods [4,21]. Although both methods are used frequently in pharmacological studies, they are not without limitations [3,14,19], including lack of an auto- mated detection of the end-point (hot plate), stimulation of a unique, scaly form of non-gla- ’ J. Joris is a research assistant for the National Fund for Scientific Research (Belgium). Correspondence to: Dr. Kenneth Hargreaves, NAB, NIDR, NIH, Building 10, Room lA09, 9000 Rockville Pike, Bethesda, MD 20892, U.S.A. brous skin (tail flick), and lack of laterality which removes the possibility of within-subject controls (both methods). In addition, neither method has been extended to investigating behavioral re- sponses to hyperalgesia. Quantitation of behavioral responses to cuta- neous hyperalgesia has relied upon the Randall and Selitto method which uses mechanical force as the nociceptive stimulus [12]. However, this method also has several limitations. Since mecha- nical stimuli activate both low and high threshold mechanoreceptors in cutaneous and non-cuta- neous tissue [5,9,16], the relative contribution of each receptor to the behavioral response detected by this test is unknown. The Randall and Selitto method uses a non-automated detection of the behavioral end-point which requires substantial observer interaction [6]. In addition, the method requires the animal to be restrained, providing a stimulus which activates both the pituitary-adrenal