Anesthesia in the Spinal Cord

General anesthesia is a bodily state typically induced during surgical procedures for its ability to cause unconsciousness, block memory formation, suppress thermoregulation, and inhibit autonomic responses (including the motor response) to noxious stimulation. While the regions that govern these actions can all be traced to the brain, and it is true that anesthetic agents primarily affect neural functioning, it is a misconception that anesthetics only affect the brain. After all, the central nervous system is made up of the brain and the spinal cord. Preclinical experiments done in rats demonstrate cryogenic lesions to the parietal cortex of the brain does not affect the minimum alveolar concentration (MAC, or the amount of anesthetic agent required for anesthesia) of halothane. [1] Additionally, in goats whose brains but not their spinal cords received isoflurane anesthesia, the MAC of isoflurane required to block the somatic motor response increased nearly three-fold compared to goats who received isoflurane anesthesia to the entire neuraxis. [2] These experiments suggest that anesthesia also acts at the level of the spinal cord, contrary to what was previously assumed.

Research has defined three physiological cell types in the spinal dorsal horn of the spinal cord which appear to be involved in processing somatosensory information. Painful stimuli evoke responses in high-threshold (HT) neurons, which are only activated by stimulation of their peripheral receptive fields, and wide-dynamic range (WDR) neurons, which respond in a graded fashion to both non-noxious and noxious stimuli. On the other hand, non-painful stimuli evoke responses in low-threshold (LT) and WDR neurons. [3] In one Japanese study, cats exposed to a noxious stimulus exhibited notable excitation of WDR neurons in the spinal dorsal horn. This excitation, as well as the behavioral output, was dose-dependently depressed by sevoflurane, indicating general anesthesia affects these sensory neurons in the spinal cord to inhibit pain signaling and pain-evoked movements. [4] Extracellular recordings of activity in feline spinal dorsal horn neurons showed significant reduction in the receptive fields of low-threshold neurons after propofol administration. [5] A similar finding of decreased receptive field size was found for low-threshold neurons in the rat spinal dorsal horn after halothane injection. [6] Together, these findings suggest the somatic motor response is strongly influenced by neurons in the spinal dorsal horn, and this relationship can be impaired through the effects of anesthesia at the level of the spinal cord.

Studies on the rat spinal cord have identified a group of pharmacological responses that are caused by anesthesia. These include the monosynaptic response (MSR, which is thought to be mediated by AMPA/kainate receptors), early slow ventral-root potential (early sVRP, which is believed to be mediated by NMDA receptors), late sVRP (which is thought to involve metabotropic receptors of more than one type, including tachykinin NK 1 receptors), and dorsal-root potential (DRP, which is believed to be mediated by GABAA receptors but with intervening glutamate-activated interneurons). [3] A number of anesthetic agents were examined for their effect on these responses; they consisted of propofol, the barbiturates pentobarbital and thiopental, isoflurane, ketamine, the ɑ2-adrenoreceptor agonists dexmedetomidine and clonidine, and the anesthetic cyclobutane. Of these agents, only propofol and the barbiturates strongly enhanced DRP measures, suggesting that these anesthetics affect GABAA receptors in the spinal cord. Furthermore, isoflurane and cyclobutane were both found to depress MSR, indicating their effect on the spinal cord is primarily completed through mediation of AMPA/kainate receptors. [3]

The spinal cord is an important target of anesthesia, and the significance of its response is not to be overshadowed by that of the cerebral cortex. The spinal cord is also a particularly valuable tool to study the pharmacology and physiology behind the anesthetic-evoked changes in the somatic motor response. Because the extant literature largely circles around animal studies, it would be interesting, not to mention critical, to see this topic being replicated in the clinical sphere.

References

1. Todd, Michael M., et al. “A Focal Cryogenic Brain Lesion Does Not Reduce the Minimum Alveolar Concentration for Halothane in Rats.” Anesthesiology, vol. 79, no. 1, July 1993, pp. 139–43. DOI.org (Crossref), https://doi.org/10.1097/00000542-199307000-00020

2. Antognini, Joseph F., and Kevin Schwartz. “Exaggerated Anesthetic Requirements in the Preferentially Anesthetized Brain.” Anesthesiology, vol. 79, no. 6, Dec. 1993, pp. 1244–49. DOI.org (Crossref), https://doi.org/10.1097/00000542-199312000-00015

3. Collins, J. G., et al. “Anesthetic Actions within the Spinal Cord: Contributions to the State of General Anesthesia.” Trends in Neurosciences, vol. 18, no. 12, Dec. 1995, pp. 549–53. ScienceDirect, https://doi.org/10.1016/0166-2236(95)98377-B

4. Nagasaka, H., et al. “Effects of Sevoflurane on Spinal Dorsal Horn WDR Neuronal Activity in Cats.” Masui The Japanese journal of anesthesiology, vol. 42, no. 11, Nov. 1993, pp. 1647–52

5. Kishikawa, K., et al. “Low-Threshold Neuronal Activity of Spinal Dorsal Horn Neurons Increases During REM Sleep in Cats: Comparison with Effects of Anesthesia.” Journal of Neurophysiology, vol. 74, no. 2, Aug. 1995, pp. 763–69. DOI.org (Crossref), https://doi.org/10.1152/jn.1995.74.2.763

6. Yamamori, Y., et al. “Halothane Effects on Low-Threshold Receptive Field Size of Rat Spinal Dorsal Horn Neurons Appear to Be Independent of Supraspinal Modulatory Systems.” Brain Research, vol. 702, no. 1, Dec. 1995, pp. 162–68. ScienceDirect, https://doi.org/10.1016/0006-8993(95)01037-7