Behavioral confirmation of “diffuse noxious inhibitory controls” (DNIC) and evidence for a role of endogenous opiates

Abstract

Earlier studies by this groupS, 9 have shown that a wide variety of noxious peripheral stimuli by mechanical, thermal or visceral-chemical agents induce a powerful inhibition of spinal dorsal horn convergent unit response to transcutaneous electrical stimuli. Conditioning stimuli must be of an area distal to the receptive field of the cell recorded and inhibition is seen simultaneously with and briefly after the conditioning stimulus. It is essential that the intensity of the conditioning stimulus be far in excess of the conditioned stimulus. This inhibition was termed DNIC, for Diffuse Noxious Inhibitory Controls, and has subsequently been shown to be antagonized by a low dose of the opiate antagonist naloxone 7. In order to determine whether this phenomenon was behaviorally significant, and not merely an electrophysiological epiphenomenon, a behavioral paradigm was designed to determine: (i) whether painful visceral stimulation could mask a complex, centrally integrated response to a punctual noxious stimulus, and (ii) whether such inhibition was reduced by moderate doses of naloxone. Since noxious visceral stimulation was shown to be particularly effective in inducing DNIC, we used the algesic agent phenylbenzoquinone (PBQ), employed in the classical murine writhing test n, as a conditioning stimulus. This drug seemed particularly appropriate due to its long duration of action, concurrent with which various pharmacologic agents could be tested. The vocalization threshold test was chosen as the conditioned stimulus since we consider that it provides a complex and centrally integrated test for the measurement of pain 2,4. Unlike the tail-flick test, it is not merely a function of spinal reflex mechanisms, and unlike tests requiring escape or other complex motor behavior, it is little affected by general condition of the animal and is not subject to 'freezing'. Male Sprague-Dawley rats weighing between 225 and 250 g were housed 5 to a cage and allowed to habituate to the laboratory for at least 48 h before testing.