From the SIR Residents and Fellows Section (RFS)

Teaching Topic: Cryoneurolysis in Patients with Refractory Chronic Peripheral Neuropathic Pain

Yoon JH, Grechushkin V, Chaudhry A, Bhattacharji P, Durkin B, Moore W. J Vasc Interv Radiol. 2016 Feb;27(2):239-43. doi: 10.1016/j.jvir.2015.11.027.

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Approximately, 15 million people in the United States and Europe experience chronic neuropathic pain. In the current climate, non-opiate based pain control is a topic of discussion among doctors and patients as well as at the national level among politicians. Therefore, studies showing efficacy of percutaneous interventions for the purpose of pain alleviation are paramount. In this study, the authors performed ultrasound guided cryoneurolysis on 22 patients with refractory peripheral neuropathic pain. Mean pain levels were 8.3 +/- 1.9 prior to intervention with a statistically significant decrease in mean pain scores at 1, 3, 6, and 12 months post procedure with repeat intervention required in 50%. This suggests this method may be efficacious for moderate term pain relief. Limitations of the study included small sample size and non-uniform concurrent pain regimens. However, the results are quite promising given the positive response to therapy and the superior safety profile of cryoneurolysis compared to alternative invasive therapies for the treatment of neuropathic pain.

Clinical Pearls

What is the basic pathophysiology of pain generation?

Nociceptors in the tissue convert a noxious stimuli to an electric impulse signaling an efferent nerve. This signal travels to the dorsal root ganglion and ascend centrally via the spinothalamic tract. Glutamate is thought to be involved in signaling at this level. The electrical signaling continues to the thalamus where it then relays the stimulus to various centers in the brain including the primary sensory cortex, periaqueductal grey, amygdala, pons and reticular formation in the brainstem among others. Under normal circumstances, inhibitory pathways in the periaqueductal grey and Lissauer tract release endogenous opioids, norepinephrine (NE), and serotonin mediated by GABA inhibitory neurons to mediate the perceived pain.

What is the pathophysiology of Cryoneurolysis on the peripheral nerve?

Temperatures of at least -30°C causes axonotmesis (disruption of the axon) and results in Wallerian degeneration of the nerve distal and slightly proximal to the induced thermal injury. There is preservation of the perineurium and epineurium and, therefore, regeneration of the nerve may occur over time. According to the authors, some studies show that the time for nerve regeneration is proportional to length of cryoablation.

Questions to Consider

What are other common percutaneous interventions available for neuropathic pain and what are their drawbacks?

Percutaneous nerve blocks are among the most common types of anesthesia for neuropathic pain. This technique typically employs a steroid/analgesic concoction to chemically decrease inflammation and axonal conduction, respectively. Drawbacks include: relatively short term relief, adverse systemic effects of corticosteroids, and possible nerve damage with subsequent neuritis.

Thermal ablation including microwave ablation and radiofrequency ablation/pulsed radiofrequency ablation cause tissue/nerve necrosis at predictable temperatures. Arguably, there is increased risk of thermal injury to potentially sensitive adjacent structures with thermal ablation.

Currently, what are the recommended first, second, and third line options for patients with neuropathic pain?

First line therapies: Tricyclic antidepressants, dual NE and serotonin reuptake inhibitors, calcium channel α2-δ ligands (gabapentin and pregabalin), and topical lidocaine.

Second line therapies: Opioid analgesics and Tramadol

Third line: Bupropion, Citalopram, Paroxetine, Antiepileptic medications, other topical ointments (i.e. capsaicin).

Additional references:
Chen H, Lamer TJ, Rho RH, Marshall KA, Sitzman BT, Ghazi SM, Brewer RP. Contemporary management of neuropathic pain for the primary care physician. Mayo Clin Proc. 2004 Dec;79(12):1533-45.

O'Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med. 2009 Oct;122(10 Suppl):S22-32.

Post Author:
Lindsay Karr Thornton, MD
SIR RFS Clinical Education Chair
University of Florida