Dysregulation of sphingolipid metabolism in pain

Abstract

Pain is a clinical condition that is currently of great concern and is often caused by tissue or nerve damage or occurs as a concomitant symptom of a variety of diseases such as cancer. Severe pain seriously affects the functional status of the body. However, existing pain management programs are not fully satisfactory. Therefore, there is a need to delve deeper into the pathological mechanisms underlying pain generation and to find new targets for drug therapy. Sphingolipids (SLs), as a major component of the bilayer structure of eukaryotic cell membranes, also have powerful signal transduction functions. Sphingolipids are abundant, and their intracellular metabolism constitutes a huge network. Sphingolipids and their various metabolites play significant roles in cell proliferation, differentiation, apoptosis, etc., and have powerful biological activities. The molecules related to sphingolipid metabolism, mainly the core molecule ceramide and the downstream metabolism molecule sphingosine-1-phosphate (S1P), are involved in the specific mechanisms of neurological disorders as well as the onset and progression of various types of pain, and are closely related to a variety of pain-related diseases. Therefore, sphingolipid metabolism can be the focus of research on pain regulation and provide new drug targets and ideas for pain.

Diagnostic Value of Menstrual Blood Lipidomics in Endometriosis: A Pilot Study

“…Ceramides, a class of sphingolipids, have been implicated in various physiological processes, including cell growth, differentiation, apoptosis, inflammation, and pain modulation [85,86]. In the context of endometriosis, ceramides have gained attention due to their potential role in the modulation of pain sensation [87,88]. Dysregulated ceramide metabolism has been linked to increased inflammation, oxidative stress, and aberrant cell signaling pathways, all of which are key features of endometriosis [84,89,90].…”

Interactions and Trends of Interleukins, PAI-1, CRP, and TNF-α in Inflammatory Responses during the Perioperative Period of Joint Arthroplasty: Implications for Pain Management—A Narrative Review

“…After peripheral nerve damage, neurons secrete chemokines, such as CCL2 [36] and CX3CL1 [36], and other immune factors, including colony-stimulating factor 1 (CSF-1) and ATP [37,38], which robustly activate astrocytes and microglia [39]. These activated glial cells subsequently release pro-inflammatory cytokines (e.g., IL-1β, TNF-α, and IL-6) [40], chemokines (e.g., CCL2) [40][41][42], ATP, excitatory amino acids (EAAs), and nitric oxide (NO) [41,[43][44][45][46].…”