BRAIN-STEM NEURONS EXPRESSING C-FOS IMMUNOREACTIVITY FOLLOWING IRRITANT CHEMICAL-STIMULATION OF THE RATS TONGUE

Many chemicals including nicotine, capsaicin and piperine (pungent che micals in red and black peppers, respectively) evoke oral pain and irr itation via largely unknown neural mechanisms. As a first step in defi ning the central pathway for oral chemical irritation, we have used an immunohistochemical method to map locations of brainstem neurons expr essing the nuclear protein, c-Fos (a putative nociceptive marker), fol lowing application of various irritants to the tongue. In barbiturate- anesthetized rats, one of the following was applied to the dorsal surf ace of the tongue: nicotine (0.5%), capsaicin (0.1%), histamine (2 or 20%), piperine (0.2%), acetylcholine (10%) or vehicle control (0.9% sa line, dH(2)O, 70% ethanol). After 2 h the rat was perfused with fixati ve and the brainstem removed, sectioned, and processed immunohistochem ically. Following application of each irritant, fos-immunoreactive nuc lei were consistently observed in the superficial dorsal horn of dorso medial trigeminal nucleus caudalis (-3 to + 0.5 mm relative to obex), interstitial (paratrigeminal) nucleus, and area postrema. Approximatel y equal numbers were observed bilaterally even with unilateral applica tion to the tongue. Fos-immunoreactive nuclei were observed in dorsome dial trigeminal caudalis bilaterally when a restricted area on the tip of the tongue was stimulated with capsaicin, but were located predomi nantly ipsilaterally following stimulation of the lateral tongue. Few or no Fos-immunoreactive nuclei were seen in these areas in control ra ts. Numbers of Fos-immunoreactive nuclei were significantly increased following nicotine and capsaicin in ventrolateral trigeminal nucleus c audalis and nucleus of the solitary tract. Fos-immunoreactivity was al so seen consistently in the ventrolateral medulla dorsal to the latera l reticular nucleus, and vestibular and cochlear nuclei, and less cons istently in nucleus raphe pallidus and inferior olive, in both irritan t and in control groups, indicating that it was not stimulus-evoked. T hese results have identified a population of neurons in the dorsomedia l trigeminal nucleus caudalis likely to be involved in signaling chemi cal irritation of the tongue; Increases in Fos-immunoreactivity observ ed in the nucleus of the solitary tract, area postrema, and ventrolate ral trigeminal caudalis also suggest roles for these areas in autonomi c responses consequent to oral irritation.