Perineural Administration of Botulinum Toxin for Chronic Pain Management: A Narrative Review

Pain Res Manag. 2026;2026(1):e6539538. doi: 10.1155/prm/6539538.

ABSTRACT

BACKGROUND: Neuropathic pain occurs as a direct consequence of a lesion or a disease affecting the somatosensory system. Because of the limited therapeutic arsenal, it is difficult to treat. Nevertheless, pain relief has been demonstrated in multiple clinical trials treating neuropathic pain patients with subcutaneous or intradermal administrations of botulinum toxin. However, this type of administration route shows limits; for example, the painful area may be too large for subcutaneous administration, or administration discomfort would be intolerable for direct injection into the painful area. For these reasons, alternative routes have been investigated, including the perineural one.

OBJECTIVE: In the present review, we critically assess currently available clinical studies on perineural botulinum toxin administration for chronic pain treatment. We also discuss its possible underlying mechanisms and compare it to those of subcutaneous botulinum toxin administration.

RESULTS: Studies demonstrated that perineural injection of botulinum toxin is an interesting alternative for the treatment of chronic pain, both for reducing pain intensity and improving quality of life. In addition to few reported side effects, compared to other pharmacological interventions, its strength also lies in its long-lasting effects.

CONCLUSION: Despite promising results, the limited available literature cannot recommend this route of administration over others. More significant results and randomized controlled clinical trials are needed to support with confidence this route of administration.

PMID:41852239 | DOI:10.1155/prm/6539538