Intradiscal Therapies for Lumbar Degenerative Disk Disease

Abstract and Introduction

Abstract

Discogenic low back pain is a common musculoskeletal complaint in patients presenting to orthopaedic surgeons. In addition to surgical options, there are several nonsurgical intradiscal treatments that have gained interest, ranging from biologic, nonbiologic, cell-based, and molecular therapies. However, there is limited evidence for many of these techniques, and some are still in the clinical trial stage. We describe a broad overview of these intradiscal therapies, the mechanism of action, and the evidence behind them.

Introduction

Low back pain secondary to degenerative disk disease (DDD) is the most prevalent musculoskeletal complaint among the adult population, affecting up to 80% of people and costing the US healthcare system between $19.6 and $118.8 billion per year.^[1] The intervertebral disk (IVD), composed of the inner nucleus pulposus (NP), the outer anulus fibrosus (AF), and the cartilaginous/boney end plates, is subject to age-related cellular, structural, and extracellular matrix (ECM) changes.^[2] Because of cell senescence, inflammatory cytokines, and degradative enzymes, the degenerating disk can be a severe source of pain.^[3]

Traditional medical management consists of conservative treatment, such as physical therapy and analgesics, or surgical treatment, such as arthrodesis or diskectomy. However, both options often result in poor outcomes and persistent pain. Subsequently, much effort has been made developing alternative intradiscal therapies to reduce pain and slow the progression of degeneration. Although accessing the disk normally requires fluoroscopy or CT guidance, newer techniques have demonstrated the feasibility of ultrasound guidance.^[4]

In this article, we will review the current progress made in intradiscal therapies for lumbar DDD, including nonbiologics, cell-based, biologics, and molecular approaches (Table 1).

Table 1. Summary of Interventions and Their Associated Levels of Evidence
Therapies	Brief Summary
Nonbiologic therapies
Intradiscal thermal procedures (level I)	Thermal ablation of nociceptive nerves within or around the disk space through the use of electrothermal or radiofrequency heating is an option for discogenic chronic low back pain.
Percutaneous disk decompression (level I)	For patients with symptomatic disk herniations, nucleus pulposus tissue is excised or ablated using suction-cutting or electrothermal devices. The resulting decrease in intradiscal pressure mitigates the disk protrusion and relieves the compressed nerve root.
Intradiscal injectables (level I)	Encompasses injection of corticosteroids, gelified ethanol, or oxygen-ozone. Anti-inflammatory effects of corticosteroids are short lived. Gelified ethanol aims to fill radial fissures while dehydrating and denaturing the nucleus and associated nerve endings. Ozone therapy has shown limited efficacy but is not currently FDA approved in the United States.
Cell therapies
Mesenchymal stem cells (MSCs) (level III)	MSCs can be sourced from bone marrow and adipose tissue to differentiate into nucleus pulposus (NP)-like cells. However, limited evidence and unclear patient indications are two current challenges MSCs face.
NP-derived cells (level I)	NP-derived cells have shown improved results compared with MSCs; however, the difficulty and invasive nature of their initial procurement poses challenges.
Biologic therapies
Platelet-rich plasma (PRP) (level III)	PRP injections use activated platelets to release growth factors thought to promote wound healing and reverse degenerative changes in the disk space. Observational studies show a benefit; however, few high-quality randomized controlled trials and a lack of culture standardization are significant challenges.
Molecular signaling (clinical trials ongoing)	Specific growth factors have the ability to modulate cellular activity and downregulate inflammatory mediators, resulting in decreased nociception and degeneration. However, the actions of these molecular signals carry the risks of unintended side effects, and growth factors are degraded rapidly by endogenous proteases.
Tissue engineering (clinical trials ongoing)	Artificial hydrogels and polymers can be used to provide structural support to the degenerated disk. These materials can also be impregnated with growth factors for additional benefit.
Future concepts
Gene therapy	Gene modification using viral carriers has been shown to increase anti-inflammatory gene transcription and reverse disk degeneration.
Novel biologics	Antibodies against neurogenic pathway targets like nerve growth factor, calcitonin-gene related peptide, and Substance P can reduce downstream effects or nociception and disk degeneration.

Table 1. Summary of Interventions and Their Associated Levels of Evidence

Therapies

Brief Summary

Nonbiologic therapies

Intradiscal thermal procedures (level I)

Thermal ablation of nociceptive nerves within or around the disk space through the use of electrothermal or radiofrequency heating is an option for discogenic chronic low back pain.

Percutaneous disk decompression (level I)

For patients with symptomatic disk herniations, nucleus pulposus tissue is excised or ablated using suction-cutting or electrothermal devices. The resulting decrease in intradiscal pressure mitigates the disk protrusion and relieves the compressed nerve root.

Intradiscal injectables (level I)

Encompasses injection of corticosteroids, gelified ethanol, or oxygen-ozone. Anti-inflammatory effects of corticosteroids are short lived. Gelified ethanol aims to fill radial fissures while dehydrating and denaturing the nucleus and associated nerve endings. Ozone therapy has shown limited efficacy but is not currently FDA approved in the United States.

Cell therapies

Mesenchymal stem cells (MSCs) (level III)

MSCs can be sourced from bone marrow and adipose tissue to differentiate into nucleus pulposus (NP)-like cells. However, limited evidence and unclear patient indications are two current challenges MSCs face.

NP-derived cells (level I)

NP-derived cells have shown improved results compared with MSCs; however, the difficulty and invasive nature of their initial procurement poses challenges.

Biologic therapies

Platelet-rich plasma (PRP) (level III)

PRP injections use activated platelets to release growth factors thought to promote wound healing and reverse degenerative changes in the disk space. Observational studies show a benefit; however, few high-quality randomized controlled trials and a lack of culture standardization are significant challenges.

Molecular signaling (clinical trials ongoing)

Specific growth factors have the ability to modulate cellular activity and downregulate inflammatory mediators, resulting in decreased nociception and degeneration. However, the actions of these molecular signals carry the risks of unintended side effects, and growth factors are degraded rapidly by endogenous proteases.

Tissue engineering (clinical trials ongoing)

Artificial hydrogels and polymers can be used to provide structural support to the degenerated disk. These materials can also be impregnated with growth factors for additional benefit.

Future concepts

Gene therapy

Gene modification using viral carriers has been shown to increase anti-inflammatory gene transcription and reverse disk degeneration.

Novel biologics

Antibodies against neurogenic pathway targets like nerve growth factor, calcitonin-gene related peptide, and Substance P can reduce downstream effects or nociception and disk degeneration.

Intradiscal Therapies for Lumbar Degenerative Disk Disease

Abstract and Introduction

Abstract

Introduction

Tables

References

Authors and Disclosures

Authors and Disclosures

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