Descending pain pathways

The diagram below shows the pathway of pain transmission from the peripheral nerves to the cerebral cortex. There are three levels of neuronal involvement and the signals may be modulated at two points during their course to the cerebral cortex. Descending inhibitory pathways arise in the midbrain and pass to the dorsal horn as shown. Multiple different neurotransmitters are involved in the pathway and include gamma-aminobutyric acid (GABA), N-methyl-D-aspartate (NMDA), noradrenaline and opioids. 

Figure 1 Descending pain modulary pathways a simplyfied diagram.

Analgesia opioids (and presumably endogenous opiopeptides) act on receptors in the periaqueductal gray region of the midbrain — activation of descending pathways to the Raphe nuclei —transmission in pain pathways. Such supraspinal analgesia appears to result largely (but not exclusively) from activation of the Li receptor subtype. 

Descending neural pathways inhibit pain perception and efferent responses to pain. The cerebral cortex, hypothalamus, thalamus and brainstem centers (periaqueductal gray [PAG], nucleus rhaphe magnus [NRM] and locus coeruleus [LC]) send descending axons to the brainstem and spinal cord that modulate pain transmission in the dorsal horn. These axonal terminals either inhibit release of noxious neurotransmitters from primary afferents, or diminish the response of second-order neurons to the noxious input. Several neurotransmitters play critical roles in... 

Figure 3.4. (1) Peripheral noxious mediators activate nociceptor endings via a process termed transduction. (2) Noxious impulses are delivered to the spinal cord dorsal horn via the process of conduction in afferent fibers, (3) The process of transmission describes synaptic transfer of noxious impulses from primary afferents to second-order cells In dorsal horn, (4) Modulation describes inhibitory and facilitatory effects of spinal interneurons on noxious transmission, (5) Descending inhibition refers to descending brainstem, midbrain, and cortical inhibitor nerve endings which supress pain transmission, (6) Cortical perception Includes neocortical sites of pain localization and limbic centers responsible for emotional and suffering components of pain, (7) Supraspinal responses Include sympathetic, neuromuscular, and neuroendocrine responses to pain. From Sinatra RS, Pain pathways. In Sinatra RS,Vlscusl G,de Leon-Casasola 0, Ginsberg B,ed. Acute Pain Management. Cambridge University Press, 2009,...

At the same time it promotes a discharge of epinephrine from the adrenal medulla, as well as discharge of catecholamines from sympathetic nerve endings, resulting in activation of spinal cord and brain descending inhibitory pain pathways. 

---