{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T11:59:11Z","timestamp":1793361551645,"version":"4.5.0"},"reference-count":15,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"University of California San Diego Faculty Senate"},{"name":"Epimed International"},{"DOI":"10.13039\/100007210","name":"Varian Medical Systems","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007210","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2025,9,18]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A previous clinical trial applied percutaneous cryoneurolysis to lower limb amputees with phantom pain. The primary outcome measure was negative, but a secondary analysis suggested that patients with a below-knee amputation (BKA) improved, while the opposite was true for above-knee amputations (AKA). We theorized two potential reasons for this difference: cryoneurolysis was inadequate for the larger sciatic nerve in the upper thigh for AKA versus the lower thigh for BKA; and BKA is innervated by only two nerves, both of which were treated while AKA involved two additional nerves left untreated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants with an existing AKA and intractable phantom pain had four nerves treated with ultrasound-guided percutaneous cryoneurolysis in the upper thigh: sciatic, femoral, obturator, lateral femoral cutaneous. For the larger nerves, we used an argon-based machine capable of inducing temperatures as low as \u2212100\u00b0C and producing a relatively large ice ball. The sciatic nerve was treated both on the anterior and posterior aspects (5.5\u2009min each). Participants were randomized to receive active or sham treatment with the option to return 4\u20136 months later for a crossover treatment. Participants and assessors were masked to treatment group allocation. Percutaneously inserted thermocouples were used to measure tissue temperature. Statistical analysis was not performed due to the limited sample size of this pilot study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After 1-month, average phantom limb pain intensity (primary outcome) was 5.0 (5.0, 6.0) in patients given cryoneurolysis (n=11) vs 5.0 (4.8, 5.3) for sham (n=5). Patients\u2019 Global Impression of Change and the Brief Pain Inventory (interference subscale) similarly suggested no improvement in either group after the initial post-treatment week. Tissue 3\u2009mm from the cryoprobe required 2.5\u2009min to reach \u221220\u00b0C and did not reach \u221240\u00b0C by the end of the freeze cycle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found no evidence that percutaneous cryoneurolysis of the four major nerves of the thigh with an argon-based machine improved lower extremity phantom pain 1\u2009month following treatment. Due to the limited sample size and probable lack of therapeutically low temperatures across the entire sciatic nerve, these results should be viewed as preliminary and used to help guide future preclinical and clinical investigations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06071715\">NCT06071715<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rapm-2025-107116","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T08:55:26Z","timestamp":1759308926000},"page":"524-532","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Cryoanalgesia to treat phantom limb pain following a trans-femoral (above-knee) amputation: a randomized, sham-controlled pilot study"],"prefix":"10.1136","volume":"51","clinical-trial-number":[{"clinical-trial-number":"nct06071715","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06071715","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6144-3273","authenticated-orcid":false,"given":"Brian M","family":"Ilfeld","sequence":"first","affiliation":[{"name":"Anesthesiology, University of California San Diego, La Jolla, California, USA"},{"name":"Outcomes Research, University of Texas, Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0955-155X","authenticated-orcid":false,"given":"John J","family":"Finneran","sequence":"additional","affiliation":[{"name":"Anesthesiology, University of California San Diego, La Jolla, California, USA"},{"name":"Outcomes Research, University of Texas, Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baharin","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Anesthesiology, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabeeca","family":"Vadakkan","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael A","family":"Alkabalan","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4443-0021","authenticated-orcid":false,"given":"Rodney A","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Anesthesiology, University of California San Diego, La Jolla, California, USA"},{"name":"Outcomes Research, University of Texas, Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"2026050502150672000_51.5.524.1","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1213\/ANE.0000000000005673","article-title":"Immediate Effects of a Continuous Peripheral Nerve Block on Postamputation Phantom and Residual Limb Pain: Secondary Outcomes From a Multicenter Randomized Controlled Clinical Trial","volume":"133","author":"Ilfeld","year":"2021","journal-title":"Anesth Analg"},{"key":"2026050502150672000_51.5.524.2","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1097\/j.pain.0000000000002087","article-title":"Ambulatory continuous peripheral nerve blocks to treat postamputation phantom limb pain: a multicenter, randomized, quadruple-masked, placebo-controlled clinical trial","volume":"162","author":"Ilfeld","year":"2021","journal-title":"Pain"},{"key":"2026050502150672000_51.5.524.3","doi-asserted-by":"crossref","first-page":"345","DOI":"10.36076\/ppj.2003\/6\/345","article-title":"Cryoanalgesia in interventional pain management","volume":"6","author":"Trescot","year":"2003","journal-title":"Pain Physician"},{"key":"2026050502150672000_51.5.524.4","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1097\/ALN.0000000000003532","article-title":"Cryoneurolysis and Percutaneous Peripheral Nerve Stimulation to Treat Acute Pain","volume":"133","author":"Ilfeld","year":"2020","journal-title":"Anesthesiology"},{"key":"2026050502150672000_51.5.524.5","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s40122-023-00497-y","article-title":"Relative Effects of Various Factors on Ice Ball Formation and Ablation Zone Size During Ultrasound-Guided Percutaneous Cryoneurolysis: A Laboratory Investigation to Inform Clinical Practice and Future 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Bursting the bubble: Does liposomal bupivacaine deliver in TAP blocks (does any local anesthetic?)? It\u2019s complicated. Anesthesiology 2025;In Press.","DOI":"10.1097\/ALN.0000000000005873"},{"key":"2026050502150672000_51.5.524.15","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1097\/ALN.0000000000005463","article-title":"Cryoneurolysis: Major Problems Rarely Discussed (or \u201cDon\u2019t Be Fooled-The Ice Ball Lies!\u201d)","volume":"142","author":"Ilfeld","year":"2025","journal-title":"Anesthesiology"}],"container-title":["Regional Anesthesia &amp; Pain Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rapm-2025-107116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T09:15:47Z","timestamp":1777972547000},"score":1,"resource":{"primary":{"URL":"https:\/\/rapm.bmj.com\/lookup\/doi\/10.1136\/rapm-2025-107116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":15,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,5]]},"published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1136\/rapm-2025-107116"],"URL":"https:\/\/doi.org\/10.1136\/rapm-2025-107116","relation":{},"ISSN":["1098-7339","1532-8651"],"issn-type":[{"value":"1098-7339","type":"print"},{"value":"1532-8651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]}}}