{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:36:49Z","timestamp":1777869409832,"version":"3.51.4"},"reference-count":90,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agave Group srl"},{"name":"Noivita Srls"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Cervical and lumbar radiculopathy and carpal tunnel syndrome (CTS) are common conditions that are associated with persistent pain, functional impairment, and reduced quality of life. Nutraceutical strategies targeting neuroinflammatory and oxidative stress pathways are being investigated as adjunctive approaches in pain management. This study evaluated the clinical association between supplementation with a Gastrodiae elata Blume-based nutraceutical formulation (Assonal\u00ae) and changes in pain intensity, functional outcomes, symptom burden, and quality of life in patients with radiculopathy and CTS. Methods: A single-centre pragmatic before\u2013after clinical study enrolled adults with cervical or lumbar radiculopathy and\/or CTS. Participants received Assonal\u00ae (two tablets daily) for two months. Pain intensity was assessed using the Numerical Pain Rating Scale (NPRS) and Visual Analogue Scale (VAS). Secondary outcomes included the Back Pain Functional Scale (BPFS), the Boston Carpal Tunnel Questionnaire (BCTQ), the Neuropathic Pain Symptom Inventory (NPSI), the EuroQol-5D-5L (EQ-5D-5L), and the Global Perceived Effect (GPE). Longitudinal within-subject changes were analysed using repeated-measures statistical tests. Results: Thirty-four participants completed the study. The observed pain intensity decreased significantly from baseline to two months (NPRS: 7.2 \u00b1 1.3 to 3.6 \u00b1 1.2; VAS: 7.3 \u00b1 2.1 to 3.3 \u00b1 1.7; p &lt; 0.0001) and functional measures showed improvements across BPFS and BCTQ assessments, accompanied by reductions in symptom burden (NPSI). Quality of life increased significantly (EQ-5D-5L index: 0.49 \u00b1 0.23 to 0.81 \u00b1 0.12; p &lt; 0.0001), and most patients reported perceived clinical improvement. Conclusions: In this exploratory real-world study, Assonal\u00ae supplementation was associated with clinically relevant improvements in pain intensity, functional performance, and quality of life in patients with radiculopathy and CTS, suggesting the need for further investigation of these associations in future controlled clinical studies.<\/jats:p>","DOI":"10.3390\/nu18091438","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:32:21Z","timestamp":1777555941000},"page":"1438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Before\u2013After Study of Gastrodia elata Blume-Based Nutraceutical Supplementation in Patients with Radiculopathy and Carpal Tunnel Syndrome"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5141-0681","authenticated-orcid":false,"given":"Marco","family":"Invernizzi","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University of Piemonte Orientale (UPO), 28100 Novara, Italy"},{"name":"Translational Medicine, Dipartimento Attivit\u00e0 Integrate Ricerca e Innovazione (DAIRI), Azienda Ospedaliero-Universitaria (AOU) SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9035-1485","authenticated-orcid":false,"given":"Lorenzo","family":"Lippi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Piemonte Orientale (UPO), 28100 Novara, Italy"},{"name":"Translational Medicine, Dipartimento Attivit\u00e0 Integrate Ricerca e Innovazione (DAIRI), Azienda Ospedaliero-Universitaria (AOU) SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Mul\u00e8","sequence":"additional","affiliation":[{"name":"Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale (UPO), Piazza Sant\u2019Eusebio 5, 13100 Vercelli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Galla","sequence":"additional","affiliation":[{"name":"Noivita Srls, Spin-Off University of Piemonte Orientale, Strada Privata Curti 7, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-8540","authenticated-orcid":false,"given":"Arianna","family":"Folli","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Piemonte Orientale (UPO), 28100 Novara, Italy"},{"name":"Translational Medicine, Dipartimento Attivit\u00e0 Integrate Ricerca e Innovazione (DAIRI), Azienda Ospedaliero-Universitaria (AOU) SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5001-3668","authenticated-orcid":false,"given":"Domenico","family":"Tiso","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, \u201cVilla Maria\u201d Hospital, 47921 Rimini, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6022-3607","authenticated-orcid":false,"given":"Francesca","family":"Parini","sequence":"additional","affiliation":[{"name":"Noivita Srls, Spin-Off University of Piemonte Orientale, Strada Privata Curti 7, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5751-270X","authenticated-orcid":false,"given":"Francesca","family":"Uberti","sequence":"additional","affiliation":[{"name":"Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale (UPO), Piazza Sant\u2019Eusebio 5, 13100 Vercelli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.pharep.2017.09.009","article-title":"Neuropathic pain models caused by damage to central or peripheral nervous system","volume":"70","author":"Kumar","year":"2018","journal-title":"Pharmacol. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.neuron.2006.09.021","article-title":"Mechanisms of neuropathic pain","volume":"52","author":"Campbell","year":"2006","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Colloca, L., Ludman, T., Bouhassira, D., Baron, R., Dickenson, A.H., Yarnitsky, D., and Raja, S.N. (2017). Neuropathic pain. Nat. Rev. Dis. Primers, 3.","DOI":"10.1038\/nrdp.2017.2"},{"key":"ref_4","first-page":"199","article-title":"Neuropathic pain: From mechanisms to treatment","volume":"100","author":"Finnerup","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_5","unstructured":"Barlow, A., and Bruera, E. (2025). Neuropathic pain. 50 Pharmacotherapy Studies Every Palliative Practitioner Should Know, Oxford University Press."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Allen, J.A. (2025). Diseases of nerve. Clinical Handbook of Neuromuscular Medicine, Springer Nature.","DOI":"10.1007\/978-3-031-70459-8_10"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1136\/practneurol-2013-000536","article-title":"Neuropathic pain: Diagnosis and treatment","volume":"13","author":"Magrinelli","year":"2013","journal-title":"Pract. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cherif, F., Zouari, H.G., Cherif, W., Hadded, M., Cheour, M., and Damak, R. (2020). Depression prevalence in neuropathic pain and its impact on quality of life. Pain Res. Manag., 2020.","DOI":"10.1155\/2020\/7408508"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.4065\/mcp.2009.0645","article-title":"Treatment considerations for patients with neuropathic pain and other medical comorbidities","volume":"85","author":"Gourlay","year":"2010","journal-title":"Mayo Clin. Proc."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bindu, S., Mazumder, S., and Bandyopadhyay, U. (2020). Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem. Pharmacol., 180.","DOI":"10.1016\/j.bcp.2020.114147"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lippi, L., Turco, A., Rudrappa, G.H., Moalli, S., de Sire, A., and Invernizzi, M. (2025). Astragalus membranaceus extract reduces functional knee joint pain: A randomized, double-blinded, placebo-controlled trial. Front. Pain Res., 6.","DOI":"10.3389\/fpain.2025.1595957"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/papr.13291","article-title":"The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review","volume":"24","author":"Frediani","year":"2024","journal-title":"Pain Pract."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1097\/j.pain.0000000000003038","article-title":"Randomized, double-blind, controlled trial of a combination of alpha-lipoic acid and pregabalin for neuropathic pain: The PAIN-CARE trial","volume":"165","author":"Gilron","year":"2024","journal-title":"Pain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1002\/cbin.12153","article-title":"Curcumin relieves oxaliplatin-induced neuropathic pain via reducing inflammation and activating antioxidant response","volume":"48","author":"Zhang","year":"2024","journal-title":"Cell Biol. Int."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yan, H., Pan, S., Zhu, L., Kong, W., and Qi, Z. (2025). Magnesium and nerve injury: Mechanisms and applications. Neural Regen. Res., online ahead of print.","DOI":"10.4103\/NRR.NRR-D-25-00263"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Invernizzi, M., Mul\u00e8, S., Lippi, L., Galla, R., Folli, A., Ferrari, S., Tiso, D., and Uberti, F. (2025). Evaluation of the clinical efficacy of a novel palmitoylethanolamide\u2013Equisetum arvense supplement for the management of chronic pain: Findings from a prospective clinical trial. Med. Sci., 13.","DOI":"10.3390\/medsci13030169"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hu, J.M., Yang, J., Yang, L., and Kuang, M.T. (2021). Medicinal orchids: Dendrobium species and Gastrodia elata Blume. Medicinal Plants and Mushrooms of Yunnan Province of China, CRC Press.","DOI":"10.1201\/9781003022770-11"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jep.2011.08.064","article-title":"The neuroprotective effects of an extract of Gastrodia elata","volume":"138","author":"Tsai","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sun, W., Miao, B., Wang, X.C., Duan, J.H., Ye, X., Han, W.J., and Hu, S.J. (2012). Gastrodin inhibits allodynia and hyperalgesia in painful diabetic neuropathy rats by decreasing excitability of nociceptive primary sensory neurons. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039647"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ferrari, S., Mul\u00e8, S., Galla, R., Brovero, A., Genovese, G., Molinari, C., and Uberti, F. (2024). Effects of nutraceutical compositions containing Rhizoma Gastrodiae or lipoic acid in an in vitro induced neuropathic pain model. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042376"},{"key":"ref_21","first-page":"249","article-title":"Neuropathic pain and chronic pain as an underestimated interdisciplinary problem","volume":"35","author":"Szewczyk","year":"2022","journal-title":"Int. J. Occup. Med. Environ. Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/mus.26510","article-title":"Integrative neuromuscular medicine: Neuropathy and neuropathic pain: Consider the alternatives","volume":"60","author":"Rowin","year":"2019","journal-title":"Muscle Nerve"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Amin, R., Alam, F., Kemisetti, D., Sarkar, D., and Dey, B.K. (2024). Carpal tunnel syndrome management by nutraceuticals. Nutraceuticals and Bone Health, Apple Academic Press.","DOI":"10.1201\/9781003415084-11"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cominelli, G., Sulas, F., Pinto, D., Rinaldi, F., Favero, G., and Rezzani, R. (2025). Neuro-nutritional approach to neuropathic pain management: A critical review. Nutrients, 17.","DOI":"10.3390\/nu17091502"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.intimp.2016.10.020","article-title":"Gastrodin relieved complete Freund\u2019s adjuvant-induced spontaneous pain by inhibiting inflammatory response","volume":"41","author":"Sun","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Xiao, M.M., Zhang, Y.Q., Wang, W.T., Han, W.J., Lin, Z., Xie, R.G., and Luo, C. (2016). Gastrodin protects against chronic inflammatory pain by inhibiting spinal synaptic potentiation. Sci. Rep., 6.","DOI":"10.1038\/srep37251"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Shao, S., Xu, C.B., Chen, C.J., Shi, G.N., Guo, Q.L., Zhou, Y., and Zhang, T.T. (2021). Divanillyl sulfone suppresses NLRP3 inflammasome activation via inducing mitophagy to ameliorate chronic neuropathic pain in mice. J. Neuroinflamm., 18.","DOI":"10.1186\/s12974-021-02178-z"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2217\/pmt-2018-0045","article-title":"Predictive factors of neuropathic pain in patients with carpal tunnel syndrome and its impact on patient activity","volume":"8","year":"2018","journal-title":"Pain Manag."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Daliri, B.O.M., Khorasani, H.M., Olia, N.D.B., Azhari, A., Shakeri, M., and Moradi, A. (2022). Association of psychological factors with limb disability in patients with cervical radiculopathy: Comparison with carpal tunnel syndrome. BMC Musculoskelet. Disord., 23.","DOI":"10.1186\/s12891-022-05593-2"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1037\/a0023580","article-title":"Using the health action process approach and implementation intentions to increase flu vaccine uptake in high-risk Thai individuals: A controlled before\u2013After trial","volume":"30","author":"Payaprom","year":"2011","journal-title":"Health Psychol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1136\/emermed-2015-204761","article-title":"Uncontrolled before\u2013after studies: Discouraged by Cochrane and the EMJ","volume":"32","author":"Goodacre","year":"2015","journal-title":"Emerg. Med. J."},{"key":"ref_32","first-page":"450","article-title":"Two-period linear mixed effects models to analyze clinical trials with run-in data when the primary outcome is continuous: Applications to Alzheimer\u2019s disease","volume":"5","author":"Wang","year":"2019","journal-title":"Alzheimers Dement."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Collister, D., Mbuagbaw, L., Guyatt, G., Devereaux, P.J., Tennankore, K.K., Reis, G., Sola, L., Xavier, D., Jha, V., and Gallagher, M. (2021). Three week compared to seven week run-in period length and the assessment of pre-randomization adherence: A study within a trial. Contemp. Clin. Trials, 107.","DOI":"10.1016\/j.cct.2021.106466"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Schmidt, W.P. (2017). Randomised and non-randomised studies to estimate the effect of community-level public health interventions: Definitions and methodological considerations. Emerg. Themes Epidemiol., 14.","DOI":"10.1186\/s12982-017-0063-5"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ray, S.S., Wilson, L.P., Khan, Z., and Patil, P.N. (2025). Effect of earmuff use on physiological and behavioral responses in preterm neonates: A non-randomized, controlled, before\u2013after, quality improvement, observational prospective cohort study. Eur. J. Pediatr., 184.","DOI":"10.1007\/s00431-025-06055-2"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mahn, F., H\u00fcllemann, P., Gockel, U., Brosz, M., Freynhagen, R., T\u00f6lle, T.R., and Baron, R. (2011). Sensory symptom profiles and co-morbidities in painful radiculopathy. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018018"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Braw, Y., Goor-Aryeh, I., and Ratmansky, M. (2025). Detecting feigned pain using an eye-tracker integrated numerical pain rating scale (NPRS). Pain Pract., 25.","DOI":"10.1111\/papr.70074"},{"key":"ref_38","first-page":"482","article-title":"Prevalence of forward head posture, neck pain and upper extremity musculoskeletal disorders among carpenters in Peshawar","volume":"5","author":"Saleem","year":"2025","journal-title":"Healer J. Physiother. Rehabil. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Schweiger, V., Schievano, C., Martini, A., Polati, L., Del Balzo, G., Simari, S., Milan, B., Finco, G., Varrassi, G., and Polati, E. (2024). Extended treatment with micron-size oral palmitoylethanolamide (PEA) in chronic pain: A systematic review and meta-analysis. Nutrients, 16.","DOI":"10.3390\/nu16111653"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"460","DOI":"10.2174\/1389200218666171031145419","article-title":"Nutraceutical approach to peripheral neuropathies: Evidence from clinical trials","volume":"19","author":"Mostacci","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, D., Liu, W., Lu, M., and Xu, Q. (2025). Neuropharmacological effects of Gastrodia elata Blume and its active ingredients. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1574277"},{"key":"ref_42","unstructured":"Dhitavat, S. (2003). Acetyl-L-Carnitine Protects Neuronal Cells: Roles In Vitro and In Vivo Experiments. [Ph.D. Thesis, University of Massachusetts Lowell]."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Virmani, M.A., and Cirulli, M. (2022). The role of L-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052717"},{"key":"ref_44","first-page":"11","article-title":"Citicoline: A novel therapeutic agent with neuroprotective, neuromodulatory, and neuroregenerative properties","volume":"2","author":"Qureshi","year":"2010","journal-title":"Nat. Med. J."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hrub\u0161a, M., Siatka, T., Nejmanov\u00e1, I., Vopr\u0161alov\u00e1, M., Kujovsk\u00e1 Kr\u010dmov\u00e1, L., Matou\u0161ov\u00e1, K., Javorsk\u00e1, L., Mac\u00e1kov\u00e1, K., Mercolini, L., and Remi\u00e3o, F. (2022). Biological properties of vitamins of the B complex, part 1: Vitamins B1, B2, B3, and B5. Nutrients, 14.","DOI":"10.3390\/nu14030484"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Orywal, K., Socha, K., Iwaniuk, P., Kaczy\u0144ski, P., Farhan, J.A., Zo\u0144, W., and Mroczko, B. (2025). Vitamins in the prevention and support therapy of neurodegenerative diseases. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031333"},{"key":"ref_47","first-page":"22","article-title":"The effect of B group vitamins (B1, B2, B5, B6, B10, B12) on the activity of antioxidant protection system enzymes and the content of lipid peroxidation products in the blood of feeding cattle","volume":"25","author":"Golovach","year":"2023","journal-title":"Sci. Messenger LNU Vet. Med. Biotechnol. Vet. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ijosm.2020.05.007","article-title":"Instrumentation used to assess pain in osteopathic interventions: A critical literature review","volume":"37","author":"Santiago","year":"2020","journal-title":"Int. J. Osteopath. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1002\/mdc3.12384","article-title":"Rating scales for pain in Parkinson\u2019s disease: Critique and recommendations","volume":"3","author":"Lyons","year":"2016","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bianchi, F., Nelson, M., Wissel, J., Kim, H., Traut, A., Shah, D., and Jabbari, B. (2025). OnabotulinumtoxinA in the management of pain in adult patients with spasticity: A systematic literature review. Toxins, 17.","DOI":"10.3390\/toxins17080418"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Alodhialah, A.M., Almutairi, A.A., and Almutairi, M. (2024). Assessing the association of pain intensity scales on quality of life in elderly patients with chronic pain: A nursing approach. Healthcare, 12.","DOI":"10.3390\/healthcare12202078"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S240","DOI":"10.1002\/acr.20543","article-title":"Measures of adult pain: Visual analog scale for pain (VAS Pain), numeric rating scale for pain (NRS Pain), McGill Pain Questionnaire (MPQ), short-form McGill Pain Questionnaire (SF-MPQ), chronic pain grade scale (CPGS), short form-36 bodily pain scale (SF-36 BPS), and measure of intermittent and constant osteoarthritis pain (ICOAP)","volume":"63","author":"Hawker","year":"2011","journal-title":"Arthritis Care Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tarekegn, T.B., Alemkere, G., and Ali, E.E. (2025). Health-related quality of life measured with EQ-5D-5L among tuberculosis patients in Addis Ababa, Ethiopia: Institutional-based cross-sectional study. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0326033"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e151","DOI":"10.1097\/CCM.0000000000006516","article-title":"The psychometric properties of the EuroQol 5D Five Level in survivors of critical illness","volume":"53","author":"Neto","year":"2025","journal-title":"Crit. Care Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"622","DOI":"10.2519\/jospt.2020.9599","article-title":"Diagnosing carpal tunnel syndrome: Diagnostic test accuracy of scales, questionnaires, and hand symptom diagrams\u2014A systematic review","volume":"50","author":"Dabbagh","year":"2020","journal-title":"J. Orthop. Sports Phys. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1179\/016164105X17260","article-title":"Boston Carpal Tunnel Questionnaire: The influence of diagnosis on patient-oriented results","volume":"27","author":"Padua","year":"2005","journal-title":"Neurol. Res."},{"key":"ref_57","unstructured":"Alam, M.A., Mohamed, A.M.E., Mohamed, R.M., Seid, A.A.A.G., and Salim, A.M. (2025). Effectiveness of chair yoga on improving quality of life among office workers with back pain: An experimental study. J. Health Wellness Community Res., 3."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"58","DOI":"10.31435\/rsglobal_wos\/28022020\/6920","article-title":"The Boston Carpal Tunnel Questionnaire (BCTQ): A reliable method for diagnosis and assessment of treatment of carpal tunnel syndrome","volume":"44","author":"Vladeva","year":"2020","journal-title":"Int. Acad. J. Web Sch."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s40266-017-0506-2","article-title":"N-of-1 randomized trials of ultra-micronized palmitoylethanolamide in older patients with chronic pain","volume":"34","author":"Germini","year":"2017","journal-title":"Drugs Aging"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"de Rooij, A., van der Leeden, M., Roorda, L.D., Steultjens, M.P., and Dekker, J. (2013). Predictors of outcome of multidisciplinary treatment in chronic widespread pain: An observational study. BMC Musculoskelet. Disord., 14.","DOI":"10.1186\/1471-2474-14-133"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Canori, A., Howard, R., Bower, J., Putrino, D., and Tabacof, L. (2025). Initial estimates of the minimal clinically important difference (MCID) for the neuropathic pain symptom inventory (NPSI): A systematic meta-analysis. medRxiv.","DOI":"10.1101\/2025.01.08.25320237"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s10072-009-0025-y","article-title":"Validation of the Italian version of the neuropathic pain symptom inventory in peripheral nervous system diseases","volume":"30","author":"Padua","year":"2009","journal-title":"Neurol. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1097\/j.pain.0000000000002130","article-title":"Stratification of patients based on the neuropathic pain symptom inventory: Development and validation of a new algorithm","volume":"162","author":"Bouhassira","year":"2021","journal-title":"Pain"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1159\/000531232","article-title":"Tolerability and efficacy of a 10:25 preparation of \u03949-tetrahydrocannabinol and cannabidiol for treatment of chronic back or neck pain: A multiple-dose escalation study","volume":"6","author":"Glare","year":"2023","journal-title":"Med. Cannabis Cannabinoids"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s40122-021-00235-2","article-title":"Management of musculoskeletal pain: An update with emphasis on chronic musculoskeletal pain","volume":"10","author":"Nalamasu","year":"2021","journal-title":"Pain Ther."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Mansfield, M., Thacker, M., Taylor, J.L., Bannister, K., Spahr, N., Jong, S.T., and Smith, T. (2023). The association between psychosocial factors and mental health symptoms in cervical spine pain with or without radiculopathy on health outcomes: A systematic review. BMC Musculoskelet. Disord., 24.","DOI":"10.1186\/s12891-023-06343-8"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Varshney, V., Osborn, J., Chaturvedi, R., Shah, V., and Chakravarthy, K. (2021). Advances in the interventional management of neuropathic pain. Ann. Transl. Med., 9.","DOI":"10.21037\/atm-20-6190"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Marcian\u00f2, G., Rania, V., Vocca, C., Palleria, C., Crudo, M., Evangelista, M., and Sre\u010dec, S. (2025). The role and safety of plant-derived nutraceuticals as adjuvant treatments for pain management: A narrative review. Nutraceuticals, 5.","DOI":"10.20944\/preprints202509.1442.v1"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"33","DOI":"10.9734\/indj\/2025\/v22i2473","article-title":"Gastrodia elata as a neuroprotective agent: A mini-review of its bioactive compounds and mechanisms of action","volume":"22","author":"Udi","year":"2025","journal-title":"Int. Neuropsychiatr. Dis. J."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Shi, H., Shi, J., Wang, Z., Zuo, H., Guo, T., Zheng, H., and Li, J. (2025). GAS reduced inflammatory responses in activated microglia by regulating the CCR2\/Akt\/GSK-3\u03b2 pathway. Mol. Brain, 18.","DOI":"10.1186\/s13041-025-01206-w"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zhang, M., Zhang, Y., Peng, J., Huang, Y., Gong, Z., Lu, H., Han, L., and Wang, D. (2024). Gastrodin against oxidative stress\u2013inflammation crosstalk via inhibiting mtDNA\/TLR9 and JAK2\/STAT3 signaling to ameliorate ischemic stroke injury. Int. Immunopharmacol., 141.","DOI":"10.1016\/j.intimp.2024.113012"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ejpain.2003.09.004","article-title":"Minimal clinically important changes in chronic musculoskeletal pain intensity measured on a numerical rating scale","volume":"8","author":"Salaffi","year":"2004","journal-title":"Eur. J. Pain"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1038\/s41401-025-01492-z","article-title":"Gastrodin promotes CNS myelinogenesis and alleviates demyelinating injury by activating the PI3K\/AKT\/mTOR signaling pathway","volume":"46","author":"Shi","year":"2025","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Tan, W., Zheng, Q., Feng, K., Feng, X., Zhong, W., Liao, C., Li, S., Liu, Y., and Hu, W. (2022). Neuroprotection of Gastrodia elata polyphenols against H2O2-induced PC12 cell cytotoxicity by reducing oxidative stress. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1050775"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jhsa.2022.03.009","article-title":"Establishing the minimal clinically important difference and substantial clinical benefit for the pain visual analog scale in a postoperative hand surgery population","volume":"47","author":"Randall","year":"2022","journal-title":"J. Hand Surg."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Scaturro, D., Vitagliani, F., Tomasello, S., Sconza, C., Respizzi, S., and Letizia Mauro, G. (2023). Combined rehabilitation with alpha-lipoic acid, acetyl-L-carnitine, resveratrol, and cholecalciferol in discogenic sciatica in young people: A randomized clinical trial. Medicina, 59.","DOI":"10.3390\/medicina59122197"},{"key":"ref_77","unstructured":"Gao, F.X., and Ren, Z.X. (2020). Dexamethasone combined with gastrodin in the treatment of chronic migraine. Spec. Health, 25."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Zhou, X., Shao, J., Xie, X., Xu, Y., Shao, T., and Jin, Z. (2022). Effectiveness of gastrodin for migraine: A meta-analysis. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.939401"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Wang, X., Zhang, B., Li, X., Liu, X., Wang, S., Xie, Y., Pi, J., Yang, Z., Li, J., and Jia, Q. (2021). Mechanisms underlying gastrodin alleviating vincristine-induced peripheral neuropathic pain. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.744663"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"996","DOI":"10.2174\/138920008786927794","article-title":"Evolutionary advantage and molecular modes of action of multi-component mixtures used in phytomedicine","volume":"9","author":"Wink","year":"2008","journal-title":"Curr. Drug Metab."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Abdelrahman, K.M., and Hackshaw, K.V. (2021). Nutritional supplements for the treatment of neuropathic pain. Biomedicines, 9.","DOI":"10.3390\/biomedicines9060674"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1142\/S0192415X25500302","article-title":"The pharmacological effects of gastrodin and the progress in the treatment of neurological disorders","volume":"53","author":"Guo","year":"2025","journal-title":"Am. J. Chin. Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zhou, R., Wang, Y., Cao, X., Yuan, X., Li, L., and Zhang, W. (2025). Gastrodin from Gastrodia elata Blume alleviates neuronal inflammation and injury via regulating the NOX2\/Nrf2 balance. Neuropharmacology, 279.","DOI":"10.1016\/j.neuropharm.2025.110620"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Yongguang, L., Xiaowei, W., Huichao, Y., and Yanxiang, Z. (2022). Gastrodin promotes the regeneration of peripheral nerves by regulating the miR-497\/BDNF axis. BMC Complement. Med. Ther., 22.","DOI":"10.1186\/s12906-021-03483-z"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s11606-019-05476-8","article-title":"Surgical Management of Lumbar Radiculopathy: A Systematic Review","volume":"35","author":"Clark","year":"2020","journal-title":"J. Gen. Intern. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Vanti, C., Turone, L., Panizzolo, A., Guccione, A.A., Bertozzi, L., and Pillastrini, P. (2021). Vertical Traction for Lumbar Radiculopathy: A Systematic Review. Arch. Physiother., 11.","DOI":"10.1186\/s40945-021-00102-5"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1097\/AJP.0b013e31828441fb","article-title":"The Effectiveness of Conservative Treatment for Patients with Cervical Radiculopathy: A Systematic Review","volume":"29","author":"Thoomes","year":"2013","journal-title":"Clin. J. Pain"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/j.apmr.2025.04.002","article-title":"Conservative Treatments of Carpal Tunnel Syndrome: A Systematic Review and Network Meta-analysis","volume":"106","author":"Chen","year":"2025","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Cassanego, G., Rodrigues, P., De Freitas Bauermann, L., and Trevisan, G. (2022). Evaluation of the Analgesic Effect of \u03b1-Lipoic Acid in Treating Pain Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pharmacol. Res., 177.","DOI":"10.1016\/j.phrs.2022.106075"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Cominacini, M., Valenti, M.T., Braggio, M., Caramori, A., Vedovi, E., and Dalle Carbonare, L. (2025). Unlocking Relief: Investigating the Impact of a Fixed Combination of Acetyl-L-Carnitine and Palmitoylethanolamide on Traumatic Acute Low Back Pain. Eur. J. Neurol., 32.","DOI":"10.1111\/ene.70334"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/9\/1438\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:41:55Z","timestamp":1777556515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/9\/1438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":90,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["nu18091438"],"URL":"https:\/\/doi.org\/10.3390\/nu18091438","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]}}}