{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T02:11:28Z","timestamp":1781575888728,"version":"3.54.5"},"reference-count":21,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Chronic pain management increasingly seeks objective biomarkers to complement subjective assessments. Ultra-weak photon emission (UPE), measurable via gas discharge visualization (GDV), has been proposed as a potential biomarker for various health conditions. However, the specificity of UPE measurements for pain versus comorbid conditions remains unexplored. This prospective cohort study followed 200 adults with electrodiagnostically confirmed neuropathic pain receiving cannabis therapy for 48 months. Assessments included the Numerical Rating Scale (NRS) for pain, Generalized Anxiety Disorder-7 (GAD-7) for anxiety, and Biowell UPE measurements. Cannabis therapy yielded 91.5% clinical response rate. However, UPE measurements showed striking differential validity: Biowell stress correlated strongly with GAD-7 (r = 0.579, p &lt; 0.001) but negligibly with NRS (r = 0.093, p = 0.001), representing a 6.2-fold difference. Variance explained was 33.5% for anxiety versus 0.9% for pain. ROC analysis revealed good discrimination for clinical anxiety (AUC = 0.744) but poor discrimination for pain (AUC = 0.550). Mixed-effects modeling confirmed UPE stress predicted GAD-7 (b = 1.82, p &lt; 0.001) but not NRS (b = \u22120.03, p = 0.84). These findings demonstrate that Biowell UPE measurements specifically capture psychological stress rather than nociceptive processes, with important implications for biomarker development in pain medicine. This study emphasizes the critical importance of validating proposed biomarkers against multiple related outcomes to establish specificity and appropriate clinical applications.<\/jats:p>","DOI":"10.3390\/bioengineering12121359","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"1359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ultra-Weak Photon Emission Demonstrates Specificity for Anxiety over Pain in Cannabis-Treated Chronic Neuropathic Pain: A Biomarker Validation Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8260-6492","authenticated-orcid":false,"given":"Mustafa","family":"Yassin","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Hasharon Hospital, Rabin Medical Center, Affiliated to Tel Aviv University, Petah Tikwa 4937211, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2517-4069","authenticated-orcid":false,"given":"Dror","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Hasharon Hospital, Rabin Medical Center, Affiliated to Tel Aviv University, Petah Tikwa 4937211, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Khatib","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Hasharon Hospital, Rabin Medical Center, Affiliated to Tel Aviv University, Petah Tikwa 4937211, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamza","family":"Murad","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Hasharon Hospital, Rabin Medical Center, Affiliated to Tel Aviv University, Petah Tikwa 4937211, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feras","family":"Qawasme","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Hasharon Hospital, Rabin Medical Center, Affiliated to Tel Aviv University, Petah Tikwa 4937211, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7630-5155","authenticated-orcid":false,"given":"Eitan","family":"Lavon","sequence":"additional","affiliation":[{"name":"Management Department, Hasharon Hospital, Rabin Medical Center and Clalit Health Services, Tel Aviv 6139001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.pain.2013.11.013","article-title":"Neuropathic pain in the general population: A systematic review of epidemiological studies","volume":"155","author":"Austin","year":"2014","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.pain.2004.09.012","article-title":"Core outcome measures for chronic pain clinical trials: IMMPACT recommendations","volume":"113","author":"Dworkin","year":"2005","journal-title":"Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41582-020-0362-2","article-title":"Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: Challenges and opportunities","volume":"16","author":"Davis","year":"2020","journal-title":"Nat. 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