Postamputation phantom pain is notoriously persistent with few validated treatments. Cryoneurolysis involves the application of low temperatures to reversibly ablate peripheral nerves. The authors tested the hypothesis that a single cryoneurolysis treatment would decrease phantom pain 4 months later.


The authors enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. The primary outcome was the change in average phantom pain intensity between baseline and 4 months as measured with a numeric rating scale (0 to 10), after which an optional crossover treatment was offered. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction.


Pretreatment phantom pain scores were similar in both groups, with a median [quartiles] of 5.0 [4.0, 6.0] for active treatment and 5.0 [4.0, 7.0] for sham. After 4 months, pain intensity decreased by 0.5 [–0.5, 3.0] in patients given cryoneurolysis (n = 71) versus 0 [0, 3] in patients given sham (n = 73), with an estimated difference (95% CI) of –0.1 (–1.0 to 0.7), P = 0.759. Following their statistical gatekeeping protocol, the authors did not make inferences or draw conclusions on secondary endpoints. One serious adverse event occurred after a protocol deviation in which a femoral nerve cryolesion was induced just below the inguinal ligament—instead of the sensory-only saphenous nerve—which resulted in quadriceps weakness, and possibly a fall and clavicle fracture.


Percutaneous cryoneurolysis did not decrease chronic lower extremity phantom limb pain 4 months after treatment. However, these results were based upon the authors’ specific study protocol, and since the optimal cryoneurolysis treatment parameters such as freeze duration and anatomic treatment location remain unknown, further research is warranted.

Editor’s Perspective
What We Already Know about This Topic
  • Chronic postamputation pain is relatively common and difficult to treat once established
  • Continuous neural blockade with local anesthetic may reduce symptoms of persistent postamputation pain, even beyond the offset of local anesthetic effect
  • Cryoneurolysis can reduce nociceptive transmission for a longer period of time by ablating peripheral nerves
What This Article Tells Us That Is New
  • In patients with established chronic postamputation pain, cryoneurolysis of distal sciatic and femoral nerves did not reduce pain scores at 4 months of follow-up compared to sham
  • Exploratory analysis suggested cryoneurolysis was associated with more pain among patients with transfemoral and ankle/foot amputations, but less pain among patients with transtibial amputation