Trigeminal activation and ocular autonomic dysfunction after stimulation of the posterior hypothalamus : contribution to the understanding of cluster headache
Tese de mestrado em Neuroftalmologia, apresentada 脿 Faculdade de Medicina da Universidade de Lisboa, 2008The posterior hypothalamus is responsible for the defensive-aggressive response, it is implicated in the sleep/ arousal cycling and it also receives convergent multimodal sensorial input, participating in the brains' pain network. The posterior hypothalamic area may act as the trigger of Cluster Headache attacks, as it is found to be activated in brain image studies specifically in this trigemino-autonomic cephalalgias but not in other primary headaches, such as migraine. Deep brain stimulation of the posterior hypothalamic area is an effective experimental treatment in intractable Cluster Headache patients. Cluster Headache attacks are characterized by a striking clockwise regularity, excruciating unilateral trigeminal pain and concomitant ipsilateral cranial autonomic symptoms. We aimed to develop an animal model to document the effect of PH electric stimulation on the systemic and cranial autonomic system and on the peripheral cranial pain system (the trigeminal ganglion) and to evaluate the effect of nitroglycerin in this model. Using stereotaxic co-ordinates we accessed the PH area and the gasserian ganglion in male adult Wistar rats. The PH was stimulated and activity was obtained in the gasserian ganglion at baseline and after glyceryl trinitrate. Pupil size and tearing were monitored. Firing frequency and post-trigger histograms were analysed and paired-samples T test was used to compare means before and after interventions. Mean differences in firing rates of ganglion cells between experimental conditions were significant when comparing PH stimulation with baseline (t 2.353, p 0.040), PH stimulation after nitroglycerin administration with baseline (t 2.517, p 0.030) and PH stimulation after nitroglycerin with isolated PH stimulation (t 3.017, p 0.013). Stimulation of the PH produced a long latency response of 50 to 150ms. No changes were documented in pupil size and tearing.We found an evident and consistent effect of increased trigeminal ganglion neuronal firing after electric stimulation of the PH of the rat that was potentiated by nitroglycerine without activation of the trigeminal-parasympathetic system.Although with limitations, our results demonstrate a polysynaptic circuitry connecting the PH to the trigeminal peripheral system that is facilitated by nitroglycerin, supporting the hypothesis that the PH has a role in modulating cranial pain. CH attacks are cannot be simply explained by its activation
