Possible Anti-Pain Vaccines: A Narrative Review of Emerging Strategies and Clinical Prospects

Abstract

Chronic pain affects millions of individuals globally and continues to pose a major burden on patients and healthcare systems. 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.

Keywords: analgesia; anti-pain vaccines; calcitonin gene-related peptide; chronic pain; immunotherapy; nerve growth factor; neuroimmunology; transient receptor potential vanilloid 1.

Figure 1

Comparative overview of therapeutic strategies for chronic pain. Different strategies for managing chronic pain include medication-based treatments, passive immunization (such as monoclonal antibody therapies), and active immunization (such as anti-pain vaccines). These approaches differ across several clinical parameters. Medications are typically associated with a higher incidence of side effects, a greater need for repeated dosing, increased risk of dependence or addiction, and shorter duration of effect. In comparison, passive and active immunization strategies may provide longer-lasting relief, reduced dosing frequency, and a lower risk of dependence. However, the side effect profiles and analgesic potential of immunotherapies are still not fully established. (+) minor; (++) moderate; (+++) major; (—) absent; (?) unknown.

Figure 2

Immunological strategies for the treatment of chronic pain. Active immunization using anti-pain vaccines can stimulate the immune system to produce antibodies that target molecules involved in chronic pain, such as nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP). These molecules play key roles in nociceptive signaling observed in conditions like osteoarthritis and migraine. By neutralizing these targets, vaccine-based therapies may provide longer-lasting analgesic effects compared to conventional medications. In addition to antibody-based approaches, a future therapeutic strategy may involve the induction of immune tolerance rather than a classical immune response. This could be achieved using tolerizing vaccines that modulate T cell activity. Such an approach may help control autoimmune-mediated pain conditions, including complex regional pain syndrome (CRPS), by dampening pathological immune responses.