Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain: an update

ABSTRACT

Introduction

Current treatments for chronic pain are inadequate. Here, we provide an update on the new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain.

Areas covered

Despite the complex nature of chronic pain and its underlying mechanisms, we do know that changes in the plasticity and modality of neurons in DRGs play a pivotal role. DRG neurons are heterogenous and offer potential pain targets for different therapeutic interventions. We discuss the last advancements of these interventions, which include the use of systemic and local administrations, selective nerve drug delivery, and gene therapy. In particular, we provide updates and further details on the molecular characterization of primary sensory neurons, new analgesics entering the market, and future gene therapy approaches.

Expert opinion

DRGs and primary sensory neurons are promising targets for chronic pain treatment due to their key role in pain signaling, unique anatomical location, and the potential for different targeted therapeutic interventions.

KEYWORDS:

• Chronic pain
• dorsal root ganglia
• primary sensory neurons
• therapeutic interventions
• gene therapy

Article highlights

• Chronic pain is caused by plastic changes that occur along the sensory pathways, often beginning with peripheral sensory neurons in dorsal root ganglia (DRGs).

• Most current pain drugs are not selective for DRGs and affect their targets in multiple tissues, often leading to serious side effects.

• Targeting molecules enriched in DRG tissues or local delivery of therapeutics around or into DRG can alleviate chronic pain with minimal side effects.

• Peripheral sensory neurons are heterogenous and drive different pain sensations. Co-administration of lidocaine derivative QX-314 with capsaicin or bacterial flagellin, as well as engineered bacterial anthrax toxins, can block different types of pain.

• Gene therapy and stem cell therapies offer promising and long-lasting approaches to selectively target DRG tissue and neurons.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are supported by grants from the National Institutes of Health grants NS113243 and NS121946 to T Berta, and NS045594 to JM Zhang, and U.S. Department of Defense grants W81XWH2110756 and W81XWH2210267 to RR Ji.