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ANESTHETIC PHARMACOLOGY

Isoflurane Depresses Diffuse Noxious Inhibitory Controls in Rats Between 0.8 and 1.2 Minimum Alveolar Anesthetic Concentration

Steven L. Jinks, PhD^*, Joseph F. Antognini, MD^*,, and Earl Carstens, PhD

*Department of Anesthesiology and Pain Medicine and Section of Neurobiology, Physiology and Behavior, University of California, Davis

Address correspondence and reprint requests to Steven L. Jinks, PhD, Department of Anesthesiology TB-170, University of California, Davis, Davis, CA 95616. Address e-mail to sljinks{at}ucdavis.edu

Diffuse noxious inhibitory control (DNIC) occurs when the response to a noxious stimulus is inhibited by a second, spatially remote noxious stimulus. The minimum alveolar anesthetic concentration (MAC) to suppress movement is not altered by a second remote noxious stimulus. We hypothesized that DNIC would be depressed in the peri-MAC range. Rats were anesthetized with isoflurane, and MAC was measured. We recorded dorsal horn neuronal responses to noxious thermal stimulation of the hindpaw, with or without concomitant supramaximal noxious mechanical stimulation of the tail or contralateral hindpaw. At 0.8 MAC, the tail clamp decreased neuronal responses 70% compared with control heat-evoked responses (from 1032 ± 178 impulses per minute to 301 ± 135 impulses per minute; P < 0.05). The tail clamp had no significant effect on neuronal responses at 1.2 MAC (from 879 ± 139 impulses per minute to 825 ± 191 impulses per minute; P > 0.05). Similarly, 1.2 MAC isoflurane significantly depressed DNIC elicited by hindpaw clamping. In another group, the cervical spinal cord was reversibly blocked by cooling to determine whether the inhibition was mediated supraspinally. With spinal cord cooling, the counterstimulus-evoked inhibition was not observed at 0.8 MAC. These results suggest that DNIC involves supraspinal structures and is present at sub-MAC isoflurane concentrations but is depressed at more than 1 MAC.

IMPLICATIONS: Diffuse noxious inhibitory control (DNIC) occurs when a noxious stimulus is perceived as being less painful when a second noxious stimulus is applied elsewhere on the body. DNIC is present in anesthetized animals, although how anesthesia affects it is unknown. We found that isoflurane depressed DNIC in the transition from 0.8 to 1.2 minimum alveolar anesthetic concentration, suggesting that DNIC is depressed in the anesthetic range needed to suppress movement.

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