C-FOS EXPRESSION IN TRIGEMINAL NUCLEUS NEURONS AFTER CHEMICAL IRRITATION OF THE CORNEA - REDUCTION BY SELECTIVE BLOCKADE OF NOCICEPTOR CHEMOSENSITIVITY
S. Martinez et C. Belmonte, C-FOS EXPRESSION IN TRIGEMINAL NUCLEUS NEURONS AFTER CHEMICAL IRRITATION OF THE CORNEA - REDUCTION BY SELECTIVE BLOCKADE OF NOCICEPTOR CHEMOSENSITIVITY, Experimental Brain Research, 109(1), 1996, pp. 56-62
The distribution and number of trigeminal brainstem and higher order s
ensory neurons expressing the protein product of the proto-oncogene c-
fos after noxious stimulation of the cornea was studied in the rat usi
ng immunocytochemistry. The possibility that attenuation of nociceptiv
e messages from the cornea by diltiazem reduced Fos-like immunoreactiv
ity of spinal trigeminal neurons was also examined. A group of animals
were killed 2-3 h after corneal stimulation. One cornea was stimulate
d with: a drop of 10 mM acetic acid; with acid plus mechanical scratch
ing of the corneal epithelium; or with a drop of saline at 56 degrees
C. Half of the animals treated with acid had been pretreated ipsilater
ally with topical diltiazem (10 mM). Control rats received either sali
ne in one eye or no treatment. Another group of animals were killed 7-
8 h after stimulation with acetic acid. Fos-like immunoreactive neuron
s were counted in serial brainstem sections using an anti-Fos primary
antiserum and processed according to the avidin-biotin complex method.
In rats killed 2-3 h after corneal stimulation with acid, heat, or ac
id plus mechanical injury, labelled neurons were found in laminae I an
d II of the intermediate zone between caudalis and interpolaris subnuc
lei of the ipsilateral spinal trigeminal nucleus and, in a reduced num
ber, in the symmetrical zones of the contralateral side. In animals st
imulated with noxious heat or combined mechanical and chemical injury,
a few scattered cells were also labelled in the ipsilateral junction
between the cervical spinal cord and the caudalmost part of the trigem
inal subnucleus caudalis. In rats killed 7 h after stimulation with ac
id, stained neurons were observed in the same areas of the trigeminal
nucleus as in rats killed at shorter times, but in lower numbers; in t
hese animals, no immunoreactive cells were found in deeper laminae or
in higher sensory relay nuclei. Pretreatment with diltiazem significan
tly reduced the number of cells of the spinal trigeminal nucleus label
led after corneal stimulation with acid. The results indicate that bri
ef noxious stimulation of the cornea evoke expression of c-Fos in neur
ons of the spinal trigeminal complex. Diminution by diltiazem of the n
umber of immunreactive neurons activated by corneal irritation suggest
s that this drug, by reducing chemosensitivity of nociceptive terminal
s, decreases nociceptive inflow to central nervous structures involved
in ocular pain perception.