Isoflurane and Nociception

Wade S. Kingery, Geeta S. Agashe, Tian Z. Guo, Shigehito Sawamura, M. Frances Davies, J. David Clark, Brian K. Kobilka, Mervyn Maze
2002 Anesthesiology  
The authors recently established that the analgesic actions of the inhalation anesthetic nitrous oxide were mediated by noradrenergic bulbospinal neurons and spinal ␣ 2B adrenoceptors. They now determined whether noradrenergic brainstem nuclei and descending spinal pathways are responsible for the antinociceptive actions of the inhalation anesthetic isoflurane, and which ␣ adrenoceptors mediate this effect. Methods: After selective lesioning of noradrenergic nuclei by intracerebroventricular
more » ... rebroventricular application of the mitochondrial toxin saporin coupled to the antibody directed against dopamine ␤ hydroxylase (D␤H-saporin), the antinociceptive action of isoflurane was determined. Antagonists for the ␣ 1 and ␣ 2 adrenoceptors were injected at spinal and supraspinal sites in intact and spinally transected rats to identify the noradrenergic pathways mediating isoflurane antinociception. Null mice for each of the three ␣ 2 -adrenoceptor subtypes (␣ 2A , ␣ 2B , and ␣ 2C ) and their wild-type cohorts were tested for their antinociceptive response to isoflurane. Results: Both D␤H-saporin treatment and chronic spinal transection enhanced the antinociceptive effects of isoflurane. The ␣ 1 -adrenoceptor antagonist prazosin also enhanced isoflurane antinociception at a supraspinal site of action. The ␣ 2 -adrenoceptor antagonist yohimbine inhibited isoflurane antinociception, and this effect was mediated by spinal ␣ 2 adrenoceptors. Null mice for the ␣ 2A -adrenoceptor subtype showed a reduced antinociceptive response to isoflurane. Conclusions: The authors suggest that, at clinically effective concentrations, isoflurane can modulate nociception via three different mechanisms: (1) a pronociceptive effect requiring descending spinal pathways, brainstem noradrenergic nuclei, and supraspinal ␣ 1 adrenoceptors; (2) an antinociceptive effect requiring descending noradrenergic neurons and spinal ␣ 2A adrenoceptors; and (3) an antinociceptive effect mediated within the spinal cord for which no role for adrenergic mechanism has been found.
doi:10.1097/00000542-200202000-00023 pmid:11818770 fatcat:ya4qubtz5va5hihap5gilf6vsm