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Authors & Affiliations
Alberto Mesa-Lombardo, Nuria Garcia-Magro, Yasmina B Martin, Ángel Núñez Molina
Abstract
The trigeminal system plays a crucial role in processing somatosensory information, and its modulation is crucial for maintaining sensory homeostasis. This study investigates the inhibitory modulation of trigeminal somatosensory responses by the locus coeruleus (LC), a key brainstem nucleus that plays a critical role in many cognitive and physiological functions. Previous electrophysiological investigations have revealed a diminished ability of the LC to inhibit somatosensory responses in the caudal nucleus of the trigeminal nerve (Sp5C) of diabetic mice. The administration of noradrenaline agonists and antagonists successfully modulated the inhibitory function of the LC. Our hypothesis is that GABAergic and glycinergic neurons in the Sp5C may be also participate in the modulatory action of the LC. Using electrophysiological recordings, we examined the activity of GABAergic and glycinergic neurons within the LC while monitoring trigeminal somatosensory responses to whisker stimulation in both control and streptozotocin-induced diabetic mice, anesthetized with isoflurane. Our results reveal that GABAergic and glycinergic are under the control of noradrenergic projections from the LC. In diabetic mice, the functionality of these inhibitory circuits appears to be compromised, contributing to the observed deficiency in LC-mediated modulation and probably in the generation of neuropathic pain. We also conducted immunohistochemical experiments supporting the presence of noradrenergic receptors in GABAergic and glycinergic neurons that were altered in diabetic mice. In conclusion, the modulation exerted by the LC on the somatosensory responses in the Sp5C is not only through noradrenergic receptors on projection neurons, but also exerts its control through projections to inhibitory interneurons.