1. 2025;28;E677-E687Lumbar Medial Branch Cryoneurolysis Improves Pain and Function Versus Radiofrequency Ablation for Chronic Low Back Pain: 12-Month Randomized Pilot Study
   Randomized Pilot Study
   Martin G. Ferrillo, DO, O'Dane Brady, DC, Kasandra Cliff, MSN, Mihyun Chang, PhD, Mary DiGiorgi, PhD, and Jonathan Slonin, MD.

BACKGROUND: Chronic low back pain (CLBP) is a common condition that can be treated with radiofrequency ablation (RFA). However, RFA can be destructive to tissue surrounding the targeted nerves. Cryoneurolysis is an alternative to RFA that applies cold temperatures to disrupt nerve conduction pathways via Wallerian degeneration, allowing for nerve regrowth.

OBJECTIVES: To compare the safety and efficacy of cryoneurolysis to RFA for treatment for CLBP.

STUDY DESIGN: A randomized pilot study (NCT06016127) that received institutional review board approval from Advarra, Inc. (Pro00062787).

SETTING: A single center in the United States. 

METHODS: Eligible patients with facet-mediated CLBP underwent lumbar RFA or cryoneurolysis of the lumbar medial branch nerve. The patients were originally followed for 180 days after treatment, with an optional study extension to 360 days. Study outcomes included pain scores on the numeric rating scale (NRS), functional disability status on the Oswestry Disability Index (ODI), Patient Global Impression of Change (PGIC) score, and safety. Analyses were adjusted for baseline NRS score, gender, and tobacco use. 

RESULTS: Age, body mass index, low back pain duration, and baseline ODI scores were similarly distributed between the cryoneurolysis and RFA groups (n = 15 each). At Days 180 and 360, cryoneurolysis was associated with  significantly lower NRS pain scores vs. RFA (Day 180: least squares mean [LSM; 95% confidence interval (CI)], 3.1 [2.1-4.1] vs. 5.4 [4.3-6.4]; LSM difference [95% CI], -2.1 [-3.6, -0.5]; P = 0.01; Day 360: LSM [95% CI], 3.0 [1.4-4.7] vs. 6.1 [4.5-7.7]; LSM difference [95% CI], -2.7 [-4.7, -0.7]; P = 0.01). ODI scores were numerically lower in the cryoneurolysis group than in the RFA group at Day 180 (LSM [95% CI], 13.3 [8.9-17.7] vs. 18.1 [13.6-22.6]; LSM difference [95% CI], -4.8 [-11.4, 1.9]; P = 0.15) and significantly lower at Day 360 (LSM [95% CI], 10.1 [6.0-14.3] vs. 20.6 [16.5-24.7]; LSM difference [95% CI], -10.5 [-16.6, -4.3]; P = 0.002). The mean percent decrease in ODI score from the baseline was greatest at Day 360 in the cryoneurolysis group than in the RFA group (-21.7% vs. -4.0%; P = 0.42). More cryoneurolysis-treated patients than RFA-treated patients had “no disability” or “mild disability” at Day 360 (6/11 vs. 5/12). Cryoneurolysis was associated with lower PGIC scores vs. RFA at Day 180 (LSM [95% CI], 2.6 [1.6-3.7] vs. 3.6 [2.6-4.7]; LSM difference [95% CI], -0.98 [-2.5, 0.6]; P = 0.2) and Day 360 (LSM [95% CI], 1.7 [0.7-2.8] vs. 4.4 [3.3-5.4]; LSM difference [95% CI], -2.6 [-4.2, -1.1]; P = 0.002). After Day 180, 45.5% of patients (5/11) who underwent cryoneurolysis and 75% (9/12) who underwent RFA required more than one additional spinal injection. No serious adverse events were observed. One mild adverse event considered unrelated to study treatment was reported (a compression fracture in the cryoneurolysis group).

LIMITATIONS: The study was not blinded, and the short tip of the cryoneurolysis device restricted its use to patients with low body mass indexes. Longer device tips are in development. 

CONCLUSIONS: At 12 months after treatment for CLBP, cryoneurolysis had a favorable safety profile and led to more significant improvements in pain and functional disability than did RFA. A large multicenter trial is warranted to further investigate the effects of cryoneurolysis on CLBP.

KEY WORDS: Chronic low back pain, facet-mediated low back pain, cryoneurolysis, cryoanalgesia, cryoablation, cryotherapy, radiofrequency ablation, pain management, medial branch block