Overcoming clinical challenges of refractory neuropathic pain

ABSTRACT

Introduction

Refractory neuropathic pain (ReNP), and its definition, is widely disputed among clinicians due in part to unclear diagnosing guidelines, overall duration of neuropathic pain, and the exhaustiveness of treatment options. Usually, ReNP is defined as chronic, intractable, and unresponsive neuropathic pain that has otherwise been untreatable.

Areas covered

In this narrative review, we discuss and summarize the effectiveness of prospective ReNP research conducted over the past 10 years. This research looks at pharmacological and interventional therapies in clinical trial settings. The pharmacological therapies discussed include the use of adjuvant treatments to improve the safety and efficacy of conventional approaches. Different modalities of administration, such as injection therapy and intrathecal drug delivery systems, provide targeted drug delivery. Interventional therapies such as neuromodulation, pulse radiofrequency, and nerve lesioning are more invasive; however, they are increasingly utilized in the field, as reflected in ongoing clinical trials.

Expert opinion

Based on the current data from RCTs and systematic reviews, it is clear that single drug therapy cannot be effective and has significant limitations. Transitioning to interventional modalities that showed more promising results sooner rather than later may be even more cost efficient than attempting different conservative treatments with a high failure rate.

KEYWORDS:

• Neural ablation
• adjuvant
• drug infusion
• interventional
• intractable
• neuromodulation
• neuropathic pain
• refractory
• stimulation
• unresponsive

Article highlights

• Refractory neuropathic pain (ReNP) and its definition, along with the thresholds by which NP transitions to ReNP, is widely disputed among clinicians. ReNP patients should typically have unsuccessfully trialed at least four drugs, for at least 3 months each.

• Although pharmacological approaches are most often insufficient, the use of adjuvants has shown promise in improving efficacy and safety of more conventional treatments.

• The efficacy of nerve blocks and intrathecal injection may be explained by their targeted administration and is enhanced with repeated injections.

• Interventional therapies, albeit more invasive and expensive, are currently among the most promising treatments, with several large clinical trials published and currently ongoing.

• A deeper understanding of the etiology of NP and ReNP conditions would enable the stratification of patients based on the specific underlying pathological mechanisms, moving toward more personalized treatments.

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

This paper was not funded.