Immunocytochemical localization of the c-fos primary gene protein, Fos, was used to identify spinal cord and brain-stem sites activated by either 4-Hz or 100-Hz electroacupuncture (EA) applied to the Zusanli acupuncture points of both hind limbs in lightly anesthetized Sprague-Dawley rats. The number and distribution of Fos-immunoreactive neurons in the brain stem and spinal cord of 4-Hz and 100-Hz EA-treated rats were compared with these in anesthesia and room control rats. Compared to non-stimulated control rats or rats in which EA was applied to a non-acupuncture point, both 4-Hz and 100-Hz EA-treated groups exhibited a significantly greater number of Fos-labeled neurons in the dorsal horn of the L2 spinal cord segment, lateral parabrachial nucleus, substantia nigra, nucleus raphe pallidus, dorsal raphe, locus coeruleus, posterior pretectal nucleus, and the lateroventral periaqueductal gray. In the 4-Hz-treated group, significant increases in Fos labeling were also observed in the cuneiform nucleus, dorsal and laterodorsal subdivisions of the periaqueductal gray, habenular nucleus, arcuate hypothalamic nucleus, and the lateroventral and lateral hypothalamic nuclei as compared to non-stimulated controls. The only brain-stem nucleus that exhibited significantly increased Fos-immunoreactive neurons in 100-Hz but not 4-Hz EA was the rostolateroventral nucleus of the medulla. These results indicate that many brain-stem regions are activated by both 4-Hz and 100-Hz EA but additional brain-stem regions are selectively activated by 4-Hz EA which may relate to the opiate sensitivity of 4-Hz EA. In sum, these data identify several distinct brain-stem nuclei that may play a role in acupuncture-mediated analgesia.
Bibliographical noteFunding Information:
We thank Mr. 0. Yougren for technical support in setting up and improving the electroacupuncture paradigm. We also thank Drs. T. Fletcher and Galen Kaufman for their helpful suggestions in this research project. This work was supported by NIDA Grant DA 06687 and NIH Grants DE 06682 and NS 28016.
- Brain stem
- Periaqueductal gray
- Spinal cord