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Migraine headaches are more prevalent in women and often occur during the early phases of the menstrual cycle, implying a link between migraine and ovarian steroids. Serotonin (5-HT) and its receptors have been proposed to play a key role in the pathophysiology of migraine. The trigeminal ganglion (TG) has been proposed as a site for 5-HT synthesis based on the expression of the rate limiting enzyme in peripheral 5-HT synthesis, tryptophan hydroxylase 1 (TPH1), in female rodent trigeminal ganglia. Tryptophan hydroxylase levels vary over the estrus cycle, however, the expression and potential regulation of other enzymes involved in 5-HT synthesis has not been reported in this tissue. C57/BL6 mice of both sexes expressed TPH1 and aromatic amino acid decarboxylase (AADC), the key enzymes involved in 5-HT synthesis. Levels of both enzymes were significantly higher in juvenile males compared with females. In naturally cycling females TPH1 and AADC expression was highest during proestrus when compared with the other phases of the cycle, and this regulation was mirrored at the mRNA level. In situ hybridization experiments detected TPH1 and AADC mRNA in presumptive neurons in the trigeminal ganglion. Both key enzymes involved in the synthesis of 5-HT are expressed in mouse trigeminal ganglion and are localized to neurons. The levels of these enzymes are dependent on gender and estrus cycle stage, suggesting that ovarian steroids might play a role in the regulation of sensory neuron 5-HT synthesis., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

NADPH-diaphorase histochemical staining demonstrated a distinct neural group that might synthesize nitric oxide in the lower brainstem of rats. The NADPH-diaphorase stain revealed a Golgi-like network in the dorsomedial spinal trigeminal nucleus oralis and rostrolateral solitary tract nucleus, whereas this network was more dense in the latter nucleus. The distribution of NADPH-diaphorase-positive neurons in these areas overlapped with parts of central terminations from the chorda tympani nerve, as demonstrated with transganglionic transport of wheatgerm agglutinin conjugated horseradish peroxidase. The number of NADPH-diaphorase-positive neurons changed after chorda tympani nerve lesion relative to the contralateral side. The control value (%) was 106.0 +/- 4.9 (mean +/- S.E.M.). One hour after the nerve lesion, the value increased to 115.2 +/- 9.1 (P > 0.05). It then decreased to 83.9 +/- 5.2 two days after the lesion (P < 0.05), and remained at this reduced level for one or two weeks, 83.2 +/- 3.0 (P < 0.01) and 83.7 +/- 2.3 (P < 0.01), respectively. This statistically significant reduction recovered to control level 103.4 +/- 2.9 four weeks after the lesion. These results show that NADPH-diaphorase-positive neurons in the lower brainstem could be regulated trans-synaptically by primary afferents, possibly gustatory inputs.

Rat trigeminal neurons innervating tooth pulps were retrogradely labelled with fluorogold and analysed enzyme- and immunohistochemically for their content of substance P, calcitonin gene-related peptide, fluoride-resistant acid phosphatase, GM 1 ganglioside, carbonic anhydrase and neurofilament protein. The data showed that both small, medium-sized and large trigeminal neurons were labelled after fluorogold deposition in maxillary molar pulps, with a majority of the cells being medium-sized and large. Less than 2% of the pulpal neurons showed substance P-like immunoreactivity. Fifty-six per cent of the pulpal nerve cells were calcitonin gene-related peptide-positive. These cells were small, medium-sized and large. Only 1% of the fluorogold-labelled cells contained fluoride-resistant acid phosphatase enzyme activity. This paralleled the finding that the pulpal neurons were unstained by Griffonia simplicifolia isolectin I-B4, a plant lectin which preferentially binds to fluoride-resistant acid phosphatase-positive cells. Choleragenoid-like immunoreactivity, which identifies cells with the GM 1 ganglioside receptor, was found in 70% of the fluorogold-labelled pulpal neurons. Approximately 80% of the fluorogold-labelled cells showed RT 97-immunoreactivity. RT 97 labels neurofilament protein and is present in large light primary sensory neurons. No pulpal neurons appeared to contain carbonic anhydrase, as judged from both enzyme- and immunocytochemical observations. The findings suggest that, in the rat, trigeminal tooth pulp neurons, which according to the classical view are nociceptive, form a heterogeneous group of neurons with a minority of small cells which may contain calcitonin gene-related peptide but rarely either substance P or fluoride-resistant acid phosphatase. However, the vast majority of pulpal nerve cells appear to have sizes and cytochemical characteristics which are not generally associated with nociceptive primary sensory neurons.