Radiofrequency Ablation and Low-Dose Naltrexone in Complex Regional Pain Syndrome: A Clinical Comparison LDN CRPS

Yoon Hang Kim MD

Complex Regional Pain Syndrome (CRPS) remains one of the most challenging chronic pain conditions we encounter. Patients typically present with severe, disproportionate pain following injury or surgery, often accompanied by sensory disturbances, temperature and color changes, swelling, and motor dysfunction. The underlying pathophysiology involves both peripheral and central sensitization, with sympathetic nervous system dysregulation and neuroinflammation playing key roles.

Management requires a multidisciplinary approach combining medications, physical rehabilitation, psychological support, and sometimes interventional procedures. Two modalities that deserve attention for refractory cases are radiofrequency ablation (RFA) and low-dose naltrexone (LDN) — each targeting different aspects of the condition's complex pathophysiology.

Radiofrequency Ablation

RFA uses radiofrequency energy delivered through a needle electrode to disrupt nerve conduction. For CRPS, the typical targets are sympathetic ganglia: the stellate ganglion for upper extremity involvement, or the lumbar sympathetic chain for lower extremity cases. Continuous RFA produces thermal neurolysis, while pulsed RFA (PRF) offers neuromodulation without significant tissue destruction.

The evidence base includes case reports, retrospective series, and limited comparative studies showing prolonged pain reduction — sometimes lasting months to years — particularly in patients with sympathetically maintained pain. Systematic reviews suggest moderate evidence, though larger randomized trials are still needed.

Potential complications include temporary pain flare, numbness, paresthesia, bruising, and infection. Stellate ganglion procedures carry risk of Horner syndrome. Rare but serious complications include vascular injury, pneumothorax, and paradoxically, worsening or new-onset CRPS. Pulsed RFA generally carries lower risk than continuous thermal ablation.

Low-Dose Naltrexone

LDN — typically dosed at 1–4.5 mg daily — represents an off-label use of the opioid antagonist naltrexone. At these low doses, the mechanism shifts from opioid receptor blockade to modulation of Toll-like receptor 4 (TLR4) on glial cells. This attenuates microglial activation and reduces the neuroinflammatory cascade that drives central sensitization.

The CRPS-specific evidence comes primarily from case reports and retrospective analyses. The landmark 2013 report by Chopra and Cooper documented remission of prominent CRPS symptoms — including dystonic spasms, fixed dystonia, allodynia, and vasomotor changes — in patients who had failed conventional therapies. More recent retrospective data suggests higher response rates in patients with neuropathic pain profiles, including CRPS.

That said, high-quality randomized controlled trials specifically in CRPS remain lacking, and broader chronic pain reviews show variable results.

Side effects are generally mild and often transient: vivid dreams, drowsiness, dizziness, nausea, headache, and insomnia. These frequently resolve with continued use or dose adjustment. Serious adverse events are rare, and tolerability is high.

Comparing the Two Approaches

No head-to-head trials compare RFA and LDN in CRPS, so we're left extrapolating from their different mechanisms and available evidence.

RFA targets sympathetically mediated pain directly. For the right patient — one with a positive diagnostic sympathetic block — it can provide substantial, relatively rapid relief. However, it's invasive, requires specialized expertise, and carries procedural risks.

LDN works systemically, addressing the glial-driven neuroinflammation and central sensitization that underlie many CRPS cases. It's non-invasive, well-tolerated, and inexpensive, but benefits typically develop gradually over weeks to months.

From a safety standpoint, LDN has clear advantages: oral administration, minimal adverse effects, and very low discontinuation rates. RFA, while generally safe when performed under imaging guidance, involves inherent procedural risks.

Practical Considerations

Both interventions are typically reserved for patients who haven't responded adequately to first-line measures. Diagnostic sympathetic blocks help identify RFA candidates, while LDN often requires a trial of several weeks to months before efficacy can be assessed.

Patient selection should consider the predominant pain mechanism. Those with clear sympathetically maintained features may be better candidates for RFA, while patients with more central or inflammatory components may respond well to LDN. In practice, these aren't mutually exclusive — some patients benefit from both approaches as part of a comprehensive treatment plan.

Larger randomized trials are needed to clarify optimal protocols, comparative effectiveness, and how to best identify responders to each modality.

References

1. Chopra P, Cooper MS. Treatment of complex regional pain syndrome (CRPS) using low dose naltrexone (LDN). J Neuroimmune Pharmacol. 2013;8(3):470-476.

2. McKenzie-Brown AM, Boorman DW, Ibanez KR, Agwu E, Singh V. Low-Dose Naltrexone (LDN) for Chronic Pain at a Single Institution: A Case Series. J Pain Res. 2023;16:1993-1998.

3. Rupp A, et al. Low-dose naltrexone's utility for non-cancer centralized pain conditions: a scoping review. Pain Med. 2023;24(11):1270-1281.

4. Vuka I, et al. Interventional radiofrequency treatment for the sympathetic nervous system: a review article. Pain Ther. 2021;10(1):19-34.

5. Yang J, et al. The safety and efficacy of low-dose naltrexone in patients with fibromyalgia: a systematic review. J Pain Res. 2023;16:1017-1023.