The ascending paths of pain

Nociceptive information from the meninges and their vessels is relayed via ascending pathways , from the trigeminal sensory complex to the brainstem and diencephalon (Figure 3). Thus, anatomical and electrophysiological studies have made it possible to identify in animals projections of neurons from layers I and V of the caudal subnucleus directly towards supra-segmental structures. Their activation accounts for the different components of pain, which are the sensori-discriminatory component such as the location of the pain, its intensity and its type (throbbing, throbbing, dull, etc.), the affective-emotional component (unpleasant character of pain), and the cognitive-behavioral component (memory, attention phenomena, and motor and decision-making consequences). There are ascending connections with the nuclei of the brainstem, directly with the periaqueductal gray matter (PAG) and the parabrachial nucleus or indirectly with the rostro-ventral medulla (RVM), the nucleus raphe magnus (NRM), the locus coeruleus (LC), or the wedge-shaped nucleus (Liu et al. 2009; Robert et al. 2013). All of these structures have been shown to be activated upon nociceptive stimulation of the dura mater (Goadsby et al. 2002; Goadsby et al. 2017). Somatosensory and visceral nociceptive information from the head and orofacial structures also follow direct and indirect pathways that convey this information to the hypothalamus and thalamus (Burstein et al. 1990; Burstein et al. 1987; Malick et al. 2000; Veinante et al. 2000). At the level of the thalamus, the integration of nociceptive information is essentially done at the level of the ventral posteromedial nucleus (VPM) and the ventral posterolateral nucleus (VPL). Other nuclei, essentially linked to the limbic system, have shown their implications, such as the central, anterior and dorsal nuclei (Burstein et al. 2005). The VPM is considered to be the main thalamic relay for craniovascular afferents, before transmitting them to the upper cortical regions, in particular the S1 and S2 somatosensory areas, as well as the insula (Noseda et al. 2011). Through its connections, there is a somatotopic organization of the discriminative information coming from the trigeminal nerve and in particular from the ophthalmic branch (V1). This explains the ability of migraine patients to localize their pain with precision, as well as its intensity and its throbbing and throbbing quality. The other nuclei of the thalamus also showed anatomical projections to somatosensory areas S1 and S2, and connections to motor, visual, olfactory and auditory areas (Noseda et al. 2011). The projections of these nuclei in the integration of the pain of the headache can be at the origin of the motor and cognitive deficits observed during the migraine attack, but also of the associated signs such as photophobia, phonophobia or osmophobia. In addition to these trigeminothalamic pathways, other relays are involved in the integration of pain such as the hypothalamus or the amygdala.