Induction of Fos-like Immunoreactivity by Electrocutaneous Stimulation of the Rat Hindpaw

Stimulation of peripheral nerves activates the proto-oncogene c-fos, which in turn generates its gene product, Fos. Fos and Fos-like proteins are produced in the central nervous system in response to chemical, mechanical, thermal, and electrical manipulation. The present study demonstrated a relationship between the number of Fos-like-immunoreactive nuclei in the spinal dorsal horn and graded intensities of electrical stimulation applied to the hindpaws of anesthetized and unanesthetized rats. Stimulation levels within the range of 0.1 to 1.0 mA were chosen on the basis of parmeters previously determined in behavioral investigations of escape reactions. Focal stimulation at these intensities activates peripheral axons directly, but does not injure or traumatize peripheral tissues. There was no evidence of inflammation or edema as a result of the focal electrical stimulation. As the stimulation intensity increased, the number and distribution of Fos-like-labeled nuclei increased with respect to rostral-caudal and laminar orientation. The threshold for expression of Fos-like immunoreactivity was different for anesthetized and unanesthetized animals. For anesthetized animals, the number of labeled nuclei increased significantly from the control level only when 1.0 mA was applied. However, in unanesthetized animals, the pattern of labeling was statistically significant at 0.2 mA. The present study demonstrates that electrical stimulation can evoke the expression of Fos-like immunoreactivity by activating nociceptors in the absence of tissue injury, and that the use of anesthetics can modulate this expression.