Human molecular mechanisms of discogenic low back pain: A scoping review.

The limited understanding of the mechanisms underlying human discogenic low back pain (DLBP) has hampered the development of effective treatments. While there is much research on disc degeneration, the association between degeneration and pain is weak. Therefore, there is an urgent need to identify pain-inducing molecular mechanism to facilitate the development of mechanism-specific therapeutics. This scoping review aims to determine the current knowledge of molecular mechanisms associated with human DLBP. A systematic search on CENTRAL, CINAHL, Citation searching, ClinicalTrials.gov, Embase, Google Scholar, MEDLINE, PsycINFO, PubMed, Scopus, Web of Science, and World Health Organization was performed. Studies with human DLBP as diagnosed by discography or imaging that analyzed human disc tissues and reported pain-related outcomes were included, and those on predominant radicular pain were excluded. The search returned 6012 studies. Most studies did not collect pain-related outcomes. Those that included pain assessment relied on self-report of pain intensity and disability. Six studies qualified for data extraction and synthesis. The main molecular mechanisms associated with DLBP were the expressions of nociceptive neuropeptides and cytokines, particularly TNF-αdue to its strong association with pain outcomes. Activation of NF-κB signaling pathway, alterations in adrenoceptor expressions, and increase in reactive oxygen species (ROS) were also associated with DLBP through regulation of pro-inflammatory factors and pain-related neuropeptides. Current evidence converges to TNF-α, NF-κB signaling, and ROS-induced pro-inflammation. Major weaknesses in the current literature are the focus on degeneration without pain phenotyping, and lack of association of molecular findings with pain outcomes. PERSPECTIVE: This scoping review identified TNF-α, NF-κB signaling, and ROS-induced pro-inflammation as relevant mechanisms of human discogenic low back pain. Major weaknesses in the current literature are the focus on degeneration without pain phenotyping, and lack of association of molecular findings with pain outcomes.