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Traditional analgesics, such as opioids and nonsteroidal anti-inflammatory drugs, often provide only partial relief and are frequently associated with significant side effects and risks of misuse. In recent years, vaccines that target molecules involved in pain signaling have emerged as an innovative therapeutic strategy. These vaccines aim to induce long-lasting immune responses against key mediators of nociception, including nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), substance P, and voltage-gated sodium channels such as Nav1.7. By promoting the production of specific antibodies, anti-pain vaccines have the potential to achieve analgesic effects with longer duration, reduced need for frequent administration, and improved accessibility. Multiple vaccine platforms are under investigation, including virus-like particles, peptide-protein conjugates, and nucleic acid technologies. Although preclinical studies have shown promising efficacy and safety profiles, clinical evidence is still limited to early-stage trials, particularly for migraine. This narrative review summarizes current knowledge on therapeutic vaccines for pain, discusses the immunological and technological advances in the field, and outlines future directions.<\/jats:p>","DOI":"10.3390\/vaccines13090909","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T10:29:18Z","timestamp":1756376958000},"page":"909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Possible Anti-Pain Vaccines: A Narrative Review of Emerging Strategies and Clinical Prospects"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4220-4979","authenticated-orcid":false,"given":"Yuri Chaves","family":"Martins","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Saint Louis University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana Pereira","family":"De-Sousa","sequence":"additional","affiliation":[{"name":"<i>Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz) and Centro de Pesquisa, Diagn\u00f3stico e Treinamento em Mal\u00e1ria<\/i>, Fiocruz, and <i>Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente<\/i> (SVSA), Ministry of Health, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0727-9565","authenticated-orcid":false,"given":"Peyton J.","family":"Murin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5137-1994","authenticated-orcid":false,"given":"Hamed","family":"Sadeghipour","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Saint Louis University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e1udio Tadeu","family":"Daniel-Ribeiro","sequence":"additional","affiliation":[{"name":"<i>Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz) and Centro de Pesquisa, Diagn\u00f3stico e Treinamento em Mal\u00e1ria<\/i>, Fiocruz, and <i>Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente<\/i> (SVSA), Ministry of Health, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/j.pain.0000000000001390","article-title":"The IASP classification of chronic pain for ICD-11: Chronic primary pain","volume":"160","author":"Nicholas","year":"2019","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/S0140-6736(21)00393-7","article-title":"Chronic pain: An update on burden, best practices, and new advances","volume":"397","author":"Cohen","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1097\/j.pain.0000000000002291","article-title":"Prevalence of chronic pain among adults in the United States","volume":"163","author":"Yong","year":"2022","journal-title":"Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cell.2009.09.028","article-title":"Cellular and molecular mechanisms of pain","volume":"139","author":"Basbaum","year":"2009","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1146\/annurev-neuro-072116-031121","article-title":"Nerve growth factor and pain mechanisms","volume":"40","author":"Denk","year":"2017","journal-title":"Annu. 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