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Descending analgesia pathway and its potential role in the pathophysiology of Fibromyalgia
The descending analgesia system (also called the descending noxious inhibitory control [DNIC] pathway) is a physiologic mechanism by which the transmission of pain is inhibited at the dorsal horn and other locations within the CNS.
Projections from the origin of this pathway within the hypothalamus and PAG, utilizing enkephalin as a neurotransmitter, reach the raphe magnus nucleus within the pons and medulla.
The raphe nucleus sends projections into the dorsal horn, utilizing serotonin as a neurotransmitter, where they stimulate interneurons whose neurotransmitter is again enkephalin.
These axons innervate the presynaptic region of incoming pain fibers, leading to the presynaptic inhibition of transmission of painful sensation to second-order pain fibers, most likely through the inhibition of calcium channels.
Another part of the DNIC pathways is the locus coeruleus located in the pons. Upon stimulation by ascending pain fibers, the locus coeruleus is activated and sends projections utilizing norepinephrine as a neurotransmitter to the cortex, brainstem, and spinal cord.
This results in increased alertness and sympathetic activity and decreased pain sensation and parasympathetic activity.
The implication of the descending analgesia system in the pathophysiology of FM has been suggested by studies that have demonstrated decreased serotonin or serotonin availability within the CNS.
Additionally, metabolites of norepinephrine and dopamine are decreased in the CSF of patients with FM. This is important because there are norepinephrine-mediated pain inhibitory pathways that descend to the spinal cord and dopamine-mediated pain inhibitory pathways in the CNS that may be abnormal in FM patients.
The descending inhibitory effect is mediated by a number of neurotransmitters such as monoamines, peptides and amino acids, and by several different types of neurophysiological mechanisms acting on central terminals of primary afferent nociceptive nerve fibers, spinal interneurons, and spinal projection neurons.
The function of descending pain-inhibitory systems may be enhanced by some centrally acting drugs, direct stimulation of brain areas involved in descending inhibitory controls, indirect activation of descending pathways with peripheral stimulation or using behavioral manipulations.
Finally, it concludes that understanding of the pain-inhibitory systems may provide new pharmacological, physical, and behavioral methods for treating chronic pain.
