Treatment of chronic low back pain - new approaches on the horizon

Abstract

Back pain is the second leading cause of disability among American adults and is currently treated either with conservative therapy or interventional pain procedures. However, the question that remains is whether we, as physicians, have adequate therapeutic options to offer to the patients who suffer from chronic low back pain but fail both conservative therapy and interventional pain procedures before they consider surgical options such as discectomy, disc arthroplasty, or spinal fusion. The purpose of this article is to review the potential novel therapies that are on the horizon for the treatment of chronic low back pain. We discuss medications that are currently in use through different phases of clinical trials (I-III) for the treatment of low back pain. In this review, we discuss revisiting the concept of chemonucleolysis using chymopapain, as the first drug in an intradiscal injection to reduce herniated disc size, and newer intradiscal therapies, including collagenase, chondroitinase, matrix metalloproteinases, and ethanol gel. We also review an intravenous glial cell-derived neurotrophic growth factor called artemin, which may repair sensory nerves compressed by herniated discs. Another new drug in development for low back pain without radiculopathy is a subcutaneous monoclonal antibody acting as nerve growth factor called tanezumab. Finally, we discuss how platelet-rich plasma and stem cells are being studied for the treatment of low back pain. We believe that with these new therapeutic options, we can bridge the current gap between conservative/interventional procedures and surgeries in patients with chronic back pain.

Keywords: PRP; artemin; chemonucleolysis; chronic low back pain; clinical trials; new therapy; stem cells; tanezumab.

Figure 1

The relative proportion of the three main components of the adult human intervertebral disc; nucleus pulposus, annulus fibrosus, and the cartilage endplate. Note: Reprinted with permission from Copyright 2011 ILO’s Encyclopaedia. Roberts S, Urban S, Jill PG. Encyclopedia of Occupational Health and Safety. Intervertebral Discs. Available from: http://www.iloencyclopaedia.org/part-i-47946/musculoskeletal-system/17-6-musculoskeletal-system/intervertebral-discs.

Figure 2

Pathways of nutrient supply in a normal intervertebral disc. Notes: (A) The avascular intervertebral disc is supplied by surrounding vertebral blood vessels and nutrients must diffuse from the outside of the disc inward, down their concentration gradients. (B) Demonstrates the relationship of concentration gradients as nutrients are at their lowest concentration in the middle of the disc whereas metabolites and waste products are at their highest concentrations because of relative difficulty to diffuse out of the area. (C) Schematic showing normalized concentration gradients of glucose, oxygen, and lactic acid across the nucleus and endplate. Nutrient concentrations must remain above the critical levels to maintain cell viability and activity. Copyright ©2014. Reprinted from Nature Publishing Group. Huang YC, Urban JP, Luk KD. Intervertebral disc regeneration: do nutrients lead the way? Nat Rev Rheumatol. 2014;10(9):561–566.

Figure 3

Current common stepwise approach to management of low back pain. Notes: Initially, non-invasive measures are initiated consisting of oral medications along with non-pharmacologic measures such as physical therapy. This is followed by invasive treatments such as epidural injections or radiofrequency ablation. If these measures fail, surgical options are considered, which include discectomy or spinal fusion. Abbreviation: NSAIDs, nonsteroidal anti-inflammatory drugs.

Figure 4

Fluoroscopic image demonstrating the tungsten contrast material within the intervertebral disc, indicating adequate placement of the ethanol gel injection. Note: Reproduced from Volpentesta G, De Rose M, Bosco D, et al. Lumbar percutaneous intradiscalinjection of radiopaque gelifiedethanol (Discogel) in patients with low back and radicular pain. J Pain Relief. 2014;3:145. Creative Commons Attribution License.