Magnus raphe nucleus

The Magnus raphe nucleus (a.k.a. the Raphe magnus nucleus) is one of the raphe group of nuclei. It is a midline structure located in the brainstem, spanning the caudal pons and rostral medulla oblongata. It lies over the medial lemniscus and is situated at the same level as the facial nucleus. It is positioned directly rostral to the nucleus raphe obscurus.

The primary function of the magnus raphe nucleus is in pain modulation through descending pathways. It receives descending afferents from multiple regions, especially the periaqueductal gray, and other areas including the paraventricular hypothalamic nucleus, central nucleus of the amygdala, lateral hypothalamic area, parvocellular reticular nucleus, and cortical areas such as the prelimbic, infralimbic, medial, and lateral precentral cortices. These inputs reflect its role in mediating endogenous analgesia.

Descending fibers from the raphe magnus nucleus project to the dorsal horn of the spinal cord, where its neurons release serotonin and enkephalins, key neurotransmitters in pain inhibition. Enkephalins bind to opioid receptors on nociceptive neurons, reducing the release of excitatory neurotransmitters (e.g., glutamate and substance P) at presynaptic terminals and inducing postsynaptic hyperpolarization to decrease nociceptive neuron excitability. Serotonin enhances this effect by promoting enkephalin release or directly inhibiting substance P release. Together, these actions suppress nociceptive signaling to the brain, producing analgesia.

The raphe magnus nucleus plays an integral role in the endogenous analgesia system, particularly through its connection to the periaqueductal gray—a brain region involved in pain suppression. Stimulation of the periaqueductal gray, either electrically or via morphine administration, activates the magnus raphe nucleus to inhibit pain transmission in the dorsal horn of the spinal cord. This effect can be blocked by naloxone, an opioid receptor antagonist. Furthermore, afferent fibers from the spinothalamic tract synapse at the periaqueductal gray, providing additional pathways through which pain signals are modulated.