Microneedles for the treatment of migraine and orofacial pain: A narrative review

Headache. 2026 Mar 13. doi: 10.1111/head.70074. Online ahead of print.

ABSTRACT

BACKGROUND: Migraine is a common neurological disorder and a primary headache condition. Despite its central origin, migraine pain may be referred to the orofacial region via trigeminal pathways, resulting in phenotypic overlap with other orofacial pain (OFP) conditions. OFP represents a highly prevalent and heterogeneous group of pain disorders that substantially impair quality of life. Microneedle (MN) technology enables minimally invasive, localized, or transdermal drug delivery and has emerged as a promising mechanism-guided strategy for the management of migraine and other OFP conditions.

OBJECTIVE: This review aims to systematically summarize the current evidence on MN-based technologies for the treatment of migraine and other OFP conditions and discuss the therapeutic implications, limitations, and future directions of MN technologies.

METHODS: This study is a narrative review. PubMed/MEDLINE, Embase, Web of Science, and Google Scholar were systematically searched from inception to November 18, 2025. English-language studies evaluating MN-based technologies for migraine and other OFP conditions, including temporomandibular disorders (TMD) and oral mucosal ulcers, in animal models or human participants were included.

RESULTS: Eleven studies were included, covering migraine (n = 4), TMD (n = 2), and oral mucosal ulcers (n = 5). Across included studies, evidence for MN-based interventions was most advanced in migraine. Preclinical studies demonstrated that transdermal or intranasal MN systems enabled rapid and reliable drug absorption, with bioavailability comparable to subcutaneous injection. Clinical studies of MN-mediated triptan delivery reported high rates of 2 h pain relief and freedom from the most bothersome migraine-associated symptoms, with generally mild and transient local skin reactions. Beyond migraine, MNs were explored for TMD and oral mucosal ulcers, where they enabled localized and sustained analgesic and anti-inflammatory effects and promoted tissue healing, although evidence in these conditions remains limited and largely preclinical.

CONCLUSIONS: MN-based drug delivery represents a promising, minimally invasive strategy for migraine and other OFP management, with the strongest and most clinically relevant evidence currently available for acute migraine treatment. By enabling rapid and reliable drug absorption while bypassing gastrointestinal limitations, MNs may enhance the effectiveness of migraine-specific therapies. Emerging preclinical evidence further suggests potential applicability of MN platforms in other OFP conditions, including TMD and oral mucosal ulcers, through localized and sustained analgesic and anti-inflammatory delivery. Future research should prioritize migraine-focused optimization of MN materials and designs, alongside disease-specific expansion and standardized pain-related outcome reporting, to facilitate broader clinical translation.

PMID:41830072 | DOI:10.1111/head.70074