Targeting Inflammatory Pathways in Chronic Low Back Pain: Opportunities for Novel Therapeutics

Low back pain (LBP) is a highly prevalent musculoskeletal problem and a leading cause of disability worldwide. From a pathophysiological perspective, the contribution of inflammation to LBP is being increasingly recognized. In this literature review, we aim to provide an overview of the role of inflammation as a mediator of LBP while summarizing clinical studies investigating the potential role of anti-inflammatory treatments in the management of LBP. Although often controversial, the available evidence suggests an important role of inflammation in the pathogenesis of LBP, which can be further translated into novel therapeutic targets. Both anti-tumor necrosis factor (anti-TNF) and anti-nerve growth factor (anti-NGF) agents hold the potential of blocking inflammation and pain pathways in patients with chronic LBP. TNF inhibitors have been tested mostly in small trials with mixed results, and their long-term efficacy remains to be proven. Anti-NGF agents have demonstrated stronger and consistent efficacy in randomized controlled trials, but safety concerns compromise their widespread use. The potential role of other anti-inflammatory molecules is currently under investigation. Presently, the routine use of TNF or NGF inhibitors is not supported in radiculopathy or chronic LBP. However, novel anti-inflammatory therapies introduced in the rheumatology field appear to be promising for specific subsets of patients suffering from chronic, refractory LBP, with a complementary role as therapeutic tools, after the unsuccessful outcome of the conservative approach.