The nucleus raphe magnus (NRM) is one of the seven

raphe nuclei The raphe nuclei (, "seam") are a moderate-size cluster of nuclei found in the brain stem. They have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. They function as autoreceptors in the brain and decrease the ...

. It is situated in the

pons The pons (from Latin , "bridge") is part of the brainstem that in humans and other mammals, lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum. The pons is also called the pons Varolii ("bridge of ...

in the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...

, just rostral to the nucleus raphe obscurus. The NRM receives afferent stimuli from the enkephalinergic neurons of the

periaqueductal gray The periaqueductal gray (PAG), also known as the central gray, is a brain region that plays a critical role in autonomic function, motivated behavior and behavioural responses to threatening stimuli. PAG is also the primary control center for ...

; the serotonergic neurons of the NRM then bilaterally project efferents to the enkephalinergic and dynorphin-containing interneurons of the substantia gelatinosa of the posterior grey column of the spinal cord. This neural path thus mediates pain perception through pre-synaptic inhibition of first-order afferent (sensory) neurons.

Anatomy

Afferents

It receives afferents from the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

and

cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...

. It receives descending afferents from the periaqueductal grey matter (PAG), the paraventricular hypothalamic nucleus, central nucleus of the

amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...

, lateral hypothalamic area, parvocellular reticular nucleus and the prelimbic, infralimbic, medial and lateral precentral cortices. It is one of the afferent targets of the ascending reticular activating system.

Efferents

It projects efferents to the posterior grey column (to modulate pain).

Neurophysiology and function

The nucleus raphe magnus seems to participate in the endogenous analgesia system. Mounting evidence suggests that the nucleus raphe magnus plays an important role in homeostatic regulation. Its afferents from the

and

suggest it may be a part of the

motor system The motor system is the set of central nervous system, central and peripheral nervous system, peripheral structures in the nervous system that support motor functions, i.e. movement. Peripheral structures may include skeletal muscles and Efferen ...

.Hellman, Kevin et al., Opioid microinjection into raphe magnus modulates cardiorespiratory function in mice and rats. American Journal of Physiology Regulator Integratory Comp Physiology. Volume 297, Issue 5, November 2009, Pages R1400-8.

Pain modulation

The main function of the nucleus raphe magnus is pain mediation. The nucleus raphe magnus releases

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

when stimulated. It sends projections to the enkephalin-releasing interneurons of the posterior grey column to directly inhibit pain.Haines, Duane E., and M. D. Ard. Fundamental Neuroscience for Basic and Clinical Applications. Philadelphia, PA: Elsevier/Saunders, 2013. The periaqueductal gray (PAG), an area of the brain involved in mediating

analgesia Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...

, sends efferent stimuli to the nucleus raphe magnus when stimulated by opioids (endogenous or otherwise); electrical stimulation of the PAG as well as administration of opioid agonists to the PAG or nucleus raphe magnus produces

; the antinociceptic effects of electrical stimulation of the PAG can be blocked by administering

naloxone Naloxone, sold under the brand name Narcan among others, is an opioid antagonist, a medication used to reverse or reduce the effects of opioids. For example, it is used to restore breathing after an opioid overdose. Effects begin within two ...

(an opiate

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.spinothalamic tract The spinothalamic tract is a nerve tract in the anterolateral system in the spinal cord. This tract is an ascending sensory pathway to the thalamus. From the ventral posterolateral nucleus in the thalamus, sensory information is relayed upwar ...

synapse at the periaqueductal grey matter which in turn projects to the nucleus raphe magnus, which when stimulated directly inhibits pain fibers in the posterior grey column, alleviating pain. All of this seems to indicate that the nucleus raphe magnus is part of the endogenous opiate system, and acts to inhibit pain in the spinal cord.

References

{{Authority control Medulla oblongata Serotonin