The use of cold temperatures for analgesia has been in medical practice for thousands of years, with the first written account by Hippocrates where he described snow being carried down from high places and applied to wounds for pain control. In the 1800’s Napoleon’s surgeon general remarked on the ease and relative painless amputation of the limbs of soldiers who were exposed to the elements in Russia. Also in the 1800s, the discovery of ether and ethyl chloride spray for topical anesthesia was introduced. The modern iteration of cryoanalgesia was developed by Cooper et al. in 1962 when liquid nitrogen was introduced via a long probe targeted to specific nerves with an average temperature of -196 °C. In 1976, the first large paper showing benefit was published. Lloyd et al. demonstrated a significant reduction in pain for 52 of 64 patients with intractable pain treated with cryoanalgesia (including sciatic, intercostal, and facial nerves). The median duration of pain relief was 11 days, with some patients having significant pain relief for up to 224 days. Since this time, many delivery devices, and targets have been investigated.
The anatomy to avoid is based on the planned procedure. Care should be taken to localize the target nerve with high fidelity, using ultrasound, fluoroscopy, imaging-guided or a nerve stimulator. Additionally, care should be taken to avoid creating a lesion in proximity to the skin or large blood vessels. Motor nerves should not be lesioned; therefore, nerve stimulation is essential prior to lesioning.
Cryoanalgesia can be utilized for numerous persistent and intractable painful conditions, particularly when mediated by a peripheral nerve that can be confidently identified as the causative location. Common targets include: 
There are multiple acute pain indications for cryoanalgesia, including intra-operative cryoneurolysis of ilioinguinal and iliohypogastric nerves for postherniorrhaphy pain  and intercostal cryoneurolysis for thoracotomy pain.
However, the use of cryoneurolysis for thoracotomy pain has fallen out of favor based on increased neuropathic pain at eight weeks postoperatively, though no difference was noted at six months.
Absolute contraindications to this procedure include:
Relative contraindications include:
In the case of pneumothorax, patients should be placed on 100% oxygen to de-nitrogenate the pneumothorax (if nitrogen was used as the expansion gas). 
A small-gauge needle is needed for local infiltration of skin. The method is to localize the nerve to be blocked, including but not limited to fluoroscopy, ultrasound, and nerve stimulators. A cryo-machine with cooling agents such as nitrous oxide or carbon dioxide is needed. A 12 to 14-gauge angio-catheter is used depending on the manufacturer and size of a cryoprobe to be used, which are often 1.4 to 2 millimeters in size. Many probes incorporate a nerve stimulator in addition to the thermistor for temperature recording. A cryoprobe is compatible with cryo-machine.
Preparation and patient positioning depend largely on the target location and the implicated nerve. Access to all necessary personnel and equipment should be verified. Room temperature gas should be purged from the system. Sedation is rarely required, and heavy sedation should be avoided to facilitate patient localization of stimuli. Appropriate informed consent should be obtained. The patient should be positioned comfortably. A pre-procedural pause and time-out is then performed, identifying correct patient, side, site, and allergies. Aseptic technique should be observed.
The nerve that is to be blocked is identified with fluoroscopy, ultrasound, nerve stimulation, or other reliable methods. Next, the cryoprobe is advanced into the correct position. Many models use a sheath with a sharp stylet, which is then removed, and the cryoprobe advanced to the tip of the sheath. The sheath is then pulled back to expose the cryoprobe. Next, diagnostic nerve stimulation or diagnostic block with local anesthetic is used to confirm the correct position of the probe. If using nerve stimulation, the nerve of interest should be stimulated reliably at 0.5 volts or less, and maximum stimulation then performed to ensure lack of other nearby nerves. The probe is then activated, often with two- or three-minute freeze cycles interspersed with half-minute defrosting periods between doses, however, this can vary based on manufacturer. In general, the tissues should be allowed to recover to above 0 °C before the next freeze cycle. After the final freeze cycle, care must be taken to ensure proper thawing (greater than 120 seconds) before removal of the cryoprobe to avoid tissue damage when removing the adhered frozen tissue. A small volume of local anesthetic can then be infiltrated into the tissues as the sheath is withdrawn.
Post-procedural complications include the usual complications of interventional procedures: bleeding, infection, and damage to adjacent tissue structures like muscle (myonecrosis). With superficial procedures, damage to skin with resulting alopecia, hyper- and hypopigmentation can occur. This can be avoided by injecting saline solution to elevate the skin surface. For intercostal nerves, there are reports of neuroma formation. If pneumothorax is caused by needle placement, the expanding gas cooling agent may worsen the pneumothorax.
Cryoanalgesia has shown good postoperative pain reduction, with a possible increase in long-term pain when used intraoperatively. In a double-blind, randomized study of 55 patients cryoneurolysis provides superior postsurgical pain for intercostal cryoanalgesia compared to standard care for posterolateral thoracotomy. A second randomized controlled trial with 100 patients found similar results as well as improved pulmonary function after video-assisted thoracic surgery. Further, a 50-patient post-thoracotomy observational study found similar improvements in pain, FEV1, FVC, improved ventilation by blood gas, reduced opioid consumption, and reduced nausea and vomiting.
Long-term postoperative pain scores may be worsened with intraoperative cryoanalgesia. A double-blind, randomized study of 42 patients after posterolateral thoracotomy found increased pain scores in the cryoanalgesia arm at eight weeks and statistically more neuropathic-type pain, this resolved at six months with no difference between groups.
For chronic pain, cryoanalgesia can be effective for lumbar facet pain, intercostal neuralgia, and phantom limb pain. In a retrospective study of 91 patients who underwent cryoneurolysis for lumbar facet pain, the mean pain scores (VAS) were decreased from 7.70 to 3.72 following treatment. Pain scores continued to remain low at three months (VAS 4.99) and over the mean follow-up length of 1.7 years. In a study with 145 patients with refractory trigeminal neuralgia, cryoablation of the trigeminal nerve provided a significant improvement in pain for an average of 13 to 20 months, depending on the branch blocked. In a proof of concept study for phantom limb pain, three out of five patients had greater than 90% pain reduction at 2.5 years, and the other two had 20% to 40% pain reduction.For intercostal neuralgia, a retrospective study showed 60% of patients reported significant pain relief at the completion of the procedure, with 50% of patients continuing to have significant relief at three months.
Cryoneurolysis is an old technique with many possible future applications. Data for its use is encouraging for postoperative pain, and in select groups, for chronic pain. There is a possible increased risk of neuroma formation, and more research is required to understand this incidence. Cryoneurolysis can be another useful tool in the interventional pain specialist’s armamentarium.
Cryoanalgesia was once used by several healthcare professionals to manage pain. However, today its use is limited because of better options. Healthcare workers like the primary care provider, pain specialist, anesthesiologist, anesthesia nurse and internist who use cryoanalgesia should educate the patient on possible complications that includes neuroma formation, which can be more painful than the original pain. Follow up of patients is important to ensure that they have acquired pain relief.
|||Hsu M,Stevenson FF, Wallerian degeneration and recovery of motor nerves after multiple focused cold therapies. Muscle [PubMed PMID: 24895229]|
|||Barnard JD,Lloyd JW,Glynn CJ, Cryosurgery in the management of intractable facial pain. The British journal of oral surgery. 1978 Nov; [PubMed PMID: 214100]|
|||Cooper SM,Dawber RP, The history of cryosurgery. Journal of the Royal Society of Medicine. 2001 Apr; [PubMed PMID: 11317629]|
|||Lloyd JW,Barnard JD,Glynn CJ, Cryoanalgesia. A new approach to pain relief. Lancet (London, England). 1976 Oct 30; [PubMed PMID: 62163]|
|||Byas-Smith MG,Gulati A, Ultrasound-guided intercostal nerve cryoablation. Anesthesia and analgesia. 2006 Oct; [PubMed PMID: 17000825]|
|||Friedman T,Richman D,Adler R, Sonographically guided cryoneurolysis: preliminary experience and clinical outcomes. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2012 Dec; [PubMed PMID: 23197557]|
|||Moore W,Kolnick D,Tan J,Yu HS, CT guided percutaneous cryoneurolysis for post thoracotomy pain syndrome: early experience and effectiveness. Academic radiology. 2010 May; [PubMed PMID: 20227306]|
|||Ilfeld BM,Preciado J,Trescot AM, Novel cryoneurolysis device for the treatment of sensory and motor peripheral nerves. Expert review of medical devices. 2016 Aug; [PubMed PMID: 27333989]|
|||Trescot AM, Cryoanalgesia in interventional pain management. Pain physician. 2003 Jul; [PubMed PMID: 16880882]|
|||Johnson C,Sisante JF,Alm J,Smith M,Segal NA, Cryoneurolysis for the Treatment of Lateral Femoral Cutaneous Nerve Pain: A Case Report. PM [PubMed PMID: 31397972]|
|||Pastor J,Morales P,Cases E,Cordero P,Piqueras A,Gal�n G,Par�s F, Evaluation of intercostal cryoanalgesia versus conventional analgesia in postthoracotomy pain. Respiration; international review of thoracic diseases. 1996; [PubMed PMID: 8815972]|
|||Wolter T,Deininger M,Hubbe U,Mohadjer M,Knoeller S, Cryoneurolysis for zygapophyseal joint pain: a retrospective analysis of 117 interventions. Acta neurochirurgica. 2011 May; [PubMed PMID: 21359539]|
|||Zakrzewska JM, Cryotherapy for trigeminal neuralgia: a 10 year audit. The British journal of oral [PubMed PMID: 2004067]|
|||Fanelli RD,DiSiena MR,Lui FY,Gersin KS, Cryoanalgesic ablation for the treatment of chronic postherniorrhaphy neuropathic pain. Surgical endoscopy. 2003 Feb; [PubMed PMID: 12457217]|
|||Nelson KM,Vincent RG,Bourke RS,Smith DE,Blakeley WR,Kaplan RJ,Pollay M, Intraoperative intercostal nerve freezing to prevent postthoracotomy pain. The Annals of thoracic surgery. 1974 Sep; [PubMed PMID: 4413968]|
|||Calandria L, Cryoanalgesia for post-herpetic neuralgia: a new treatment. International journal of dermatology. 2011 Jun; [PubMed PMID: 21595675]|
|||Robbins BA,Ferrer-Bruker SJ, Notalgia Paresthetica 2020 Jan; [PubMed PMID: 29262015]|
|||Ultrasound-guided percutaneous cryoneurolysis for treatment of acute pain: could cryoanalgesia replace continuous peripheral nerve blocks?, Ilfeld BM,Gabriel RA,Trescot AM,, British journal of anaesthesia, 2017 Oct 1 [PubMed PMID: 29121277]|
|||Green CR,de Rosayro AM,Tait AR, The role of cryoanalgesia for chronic thoracic pain: results of a long-term follow up. Journal of the National Medical Association. 2002 Aug; [PubMed PMID: 12152929]|
|||Hebl JR, The importance and implications of aseptic techniques during regional anesthesia. Regional anesthesia and pain medicine. 2006 Jul-Aug; [PubMed PMID: 16857551]|
|||Evans PJ,Lloyd JW,Green CJ, Cryoanalgesia: the response to alterations in freeze cycle and temperature. British journal of anaesthesia. 1981 Nov; [PubMed PMID: 7326160]|
|||Bittman RW,Behbahani K,Gonzalez F,Prologo JD, Interventional Cryoneurolysis: What Is the Same, What Is Different, What Is New? Seminars in interventional radiology. 2019 Dec; [PubMed PMID: 31798210]|
|||Cahani D,Chacko J,Hahn B, Myonecrosis: A Rare Complication of Cryoneurolysis. The Journal of emergency medicine. 2019 Sep; [PubMed PMID: 31400988]|
|||Sepsas E,Misthos P,Anagnostopulu M,Toparlaki O,Voyagis G,Kakaris S, The role of intercostal cryoanalgesia in post-thoracotomy analgesia. Interactive cardiovascular and thoracic surgery. 2013 Jun; [PubMed PMID: 23424242]|
|||Mustola ST,Lempinen J,Saimanen E,Vilkko P, Efficacy of thoracic epidural analgesia with or without intercostal nerve cryoanalgesia for postthoracotomy pain. The Annals of thoracic surgery. 2011 Mar; [PubMed PMID: 21353017]|
|||Wolter T,Kleinmann B,Knoeller S, Cryoneurolysis for the treatment of cervical facet joint syndrome: a technical note. Journal of pain research. 2018; [PubMed PMID: 29950888]|
|||Zakrzewska JM,Nally FF, The role of cryotherapy (cryoanalgesia) in the management of paroxysmal trigeminal neuralgia: a six year experience. The British journal of oral [PubMed PMID: 3422819]|
|||Moesker AA,Karl HW,Trescot AM, Treatment of phantom limb pain by cryoneurolysis of the amputated nerve. Pain practice : the official journal of World Institute of Pain. 2014 Jan; [PubMed PMID: 23279331]|