Immunocytochemistry was used to assess the distribution of neurons within the spinal trigeminal nucleus that expressed the protein product of the proto-oncogene c-fos after thermal stimulation of the cornea in barbiturate-anesthetized rats. The influence of adrenal steroids on Fos-like immunoreactivity induced by corneal stimulation also was examined by comparison of the results obtained in adrenal intact rats to those in adrenalectomized rats and to those in adrenalectomized rats given corticosterone replacement therapy. Stimuli (42 or 52°C, 20 s per min, 15 min) were applied unilaterally to the cornea by a contact thermode. At 2 h after stimulation animals were perfused with 4% paraformaldehyde and tissue sections were incubated with primary antiserum against the Fos protein and processed with the avidin-biotin method. The pattern of Fos-like immunoreactivity after 52°C stimulation revealed a dominant group of cells ipsilaterally within the superficial laminae of the caudalmost portion of trigeminal subnucleus caudalis that was greatly enhanced in adrenalectomized rats. Low-intensity stimulation did not induce Fos-like immunoreactivity among cells in this caudal region. A second significant group of cells was seen more rostrally at periobex levels within the ventrolateral pole of the nucleus. The number of cells in the periobex grouping was increased after 52 or 42°C corneal stimulation when compared to unstimulated controls and was not affected by levels of corticosterone. The results indicated a discontinuous pattern of Fos-like immunoreactivity within the spinal trigeminal nucleus after thermal stimulation of the cornea and a differential effect of adrenal steroids. The appearance of Fos-like immunoreactivity within caudal portions of the nucleus was increased only by noxious intensities of stimulation and was further enhanced in animals with low levels of corticosterone. In contrast, the Fos-like immunoreactivity at periobex levels was increased after noxious and innocuous thermal stimuli and was independent of the level of corticosterone. The results were consistent with the hypothesis that glucocorticoids modify the expression of immediate early genes among a select group of central trigeminal neurons. Such steroid modulation may contribute to the mechanisms that underlie long-term adaptation to noxious sensory input.
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Acknowledgements-This research was supported in part by NIH grant NS 26137. Dr Hathaway was supported by NIH training grant GM 08206. The authors also thank Dr Edythe Anthony for her helpful advice.