The Role of Descending Pain Modulation in Chronic Primary Pain: Potential Application of Drugs Targeting Serotonergic System

Abstract

Chronic primary pain (CPP) is a group of diseases with long-term pain and functional disorders but without structural or specific tissue pathologies. CPP is becoming a serious health problem in clinical practice due to the unknown cause of intractable pain and high cost of health care yet has not been satisfactorily addressed. During the past decades, a significant role for the descending pain modulation and alterations due to specific diseases of CPP has been emphasized. It has been widely established that central sensitization and alterations in neuroplasticity induced by the enhancement of descending pain facilitation and/or the impairment of descending pain inhibition can explain many chronic pain states including CPP. The descending serotonergic neurons in the raphe nuclei target receptors along the descending pain circuits and exert either pro- or antinociceptive effects in different pain conditions. In this review, we summarize the possible underlying descending pain regulation mechanisms in CPP and the role of serotonin, thus providing evidence for potential application of analgesic medications based on the serotonergic system in CPP patients.

Free gait in a shallow pool accelerates recovery after exercise in model mice with fibromyalgia

“…Generally, serotonin is considered to be present in the raphe nuclei (Hornung, 2003). In addition to serotonin receptors in the brain (Hornung, 2003), serotonin also binds to receptors in the spinal dorsal horn (Tao et al, 2019;Yoshimura and Furue, 2017), which acts to inhibit pain as one of the descending inhibitory pathways (Tao et al, 2019;Yoshimura and Furue, 2017). However, the results showed no effect following exercise induction in terms of sensory threshold and locomotive behavior in this study.…”

Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020

“…HT Paracrine and Autocrine Mechanisms 5-HT activities are mediated through its interaction with 5HTRs, a superfamily with seven members (5-HT 1-7 ) and at least fourteen diverse receptor subtypes, including the most recently identified member, 5-HT 7 , which is expressed in the periphery and functions in pain processing [128]. During platelet degranulation, activated platelets secrete a significant amount of platelet-derived 5-HT that promotes vasoconstriction and stimulates activation of neighboring platelets and lymphocytes through the 5HTRs expressed on endothelial, smooth muscle, and immune cells.…”

Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020

“…5-HT activities are mediated through its interaction with 5HTRs, a superfamily with seven members (5-HT1-7) and at least fourteen diverse receptor subtypes, including the most recently identified member, 5-HT7, which is expressed in the periphery and functions in pain processing (128). During platelet degranulation, activated platelets secrete a significant amount of platelet-derived 5-HT that promotes vasoconstriction and stimulates activation of neighboring platelets and lymphocytes through the 5HTRs expressed on endothelial, smooth muscle, and immune cells.…”