Abstract

Several lines of evidence suggest that the hypothalamus is involved in trigeminal pain processing. However, the organization of descending hypothalamic projections to the spinal trigeminal nucleus caudalis (Sp5C) remains poorly understood. Microinjections of the retrograde tracer, fluorogold (FG), into the Sp5C, in rats, reveal that five hypothalamic nuclei project to the Sp5C: the paraventricular nucleus, the lateral hypothalamic area, the perifornical hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending hypothalamic projections to the Sp5C are bilateral, except those from the paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover, the density of retrogradely FG-labeled neurons in the hypothalamus varies according to the dorso-ventral localization of the Sp5C injection site. There are much more labeled neurons after injections into the ventrolateral part of the Sp5C (where ophthalmic afferents project) than after injections into its dorsomedial or intermediate parts (where mandibular and maxillary afferents, respectively, project). These results demonstrate that the organization of descending hypothalamic projections to the spinal dorsal horn and Sp5C are different. Whereas the former are ipsilateral, the latter are bilateral. Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting that these projections are preferentially involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats. Therefore, our results suggest that the control of trigeminal and spinal dorsal horn processing of nociceptive information by hypothalamic neurons is different and raise the question of the role of bilateral, rather than unilateral, hypothalamic control.

Highlights

  • Pain is a complex experience that involves sensorydiscriminative, cognitive-evaluative, and affective-emotional components

  • The Sp5C localization of FG injections was confirmed by using diaminobenzidene tetrahydrochloride (DAB): each injection appeared as a center of dense FG immunoreactivity surrounded by, first, a halo of staining with strongly FG immunoreactive neurons and more peripherally, less stained neurons (Figure 1)

  • We present the first evidence in rats that mainly five hypothalamic nuclei, the paraventricular nucleus (PVN), lateral hypothalamic area (LH), PFX, A11 and retrochiasmatic area (RCA), project to the Sp5C

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Summary

Introduction

Pain is a complex experience that involves sensorydiscriminative, cognitive-evaluative, and affective-emotional components. Evidence from neuroimaging studies in man suggest that hypothalamus is a key player in nociceptive processing, in trigeminal pain syndromes such as migraine [3] and trigeminal autonomic cephalalgias [4] including cluster headache [5,6]. This prompted the use of deep-brain stimulations to modulate this region in patients with refractory chronic cluster headache [7,8,9,10]. Animal studies, using electrophysiological recordings in rats [11,12,13] and cats [14] or Fos expression as a histochemical marker of neuronal activity [15,16,17], suggest that the hypothalamus is activated following trigeminal stimulation

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