Changing patterns of c-fos induction in spinal neurons following thermal cutaneous stimulation in the rat.

Patterns of neuronal activity in the lumbar spinal cord of the anaesthetized rat were mapped by immunocytochemical localization of the c-fos gene product, Fos protein, at different timepoints following brief noxious stimulation of one hindpaw (20 s immersion in water at 52 degrees C). After 2 h, Fos-immunoreactive neurons were seen mainly in the superficial laminae of the ipsilateral dorsal horn, with maximum somatotopic organization in lamina II. Subcutaneous injection of dilute formalin produced a similar pattern of immunostaining at 2 h, with a greater proportion of Fos-positive neurons in laminae III-VIII than with heat. With a survival time of 8 h following formalin injection, Fos immunoreactivity was virtually absent from the spinal cord. Eight hours after heat stimulation, however, the superficial pattern had given way to the appearance of a population of immunoreactive cells in the deeper laminae. The pattern of this "second wave" of heat-induced Fos-positive cells had a marked contralateral component, and was still present after 24 h, having become even more diffuse and symmetrical. The number of Fos-positive cells seen at 8 h was increased by local anaesthetic blockade of the peripheral nerve after stimulation, and reduced by continuous barbiturate anaesthesia. These findings suggest that the early stages of thermal injury trigger a complex pattern of molecular events within the spinal cord, which are initially monosynaptic and closely related to primary afferent terminal depolarization, and in the longer term the result of an induced pattern of synaptic activity set up within the spinal cord.