Topical analgesia better than oral analgesia

Professor Cruccu and colleagues studied the efficacy of a topical analgesic formulation of capsaicin and compared its effect with the oral intake of pregabalin (150–600 mg/day administered in two or three doses). They focused on the effects of both analgesic strategies on allodynia, a common peripheral neuropathic pain symptom. Allodynia in quite common in neuropathic pain disorders with prevalence of 30% and 80%, depending on the etiology of neuropathic pain. Low-threshold, mechano-sensitive C fibres (C tactile fibres), may play a role in mechanical allodynia. The authors postulated that acting on C fibres that supply the pain area, would subsequently lead to a reduction in peripheral and central sensitization and thus to subsequent attenuation of allodynia.

To directly target the C-fibers they applied a capsaicin plaster and compared the effect in a cohort of around 500 patients via a randomized, open-label, head-to-head, 8-week, non- inferiority study. They included patients from 18–80 years; with a documented diagnosis of probable or definite peripheral neuropathic pain due to post-herpetic neuralgia,  peripheral nerve injury or nondiabetic painful polyneuropathy, who had an average Numeric Pain Rating Scale score ≥4 at screening (over at least four consecutive days).

The change in intensity of allodynia, from baseline to Week 8, was  2.98 in the capsaicin group and 2.35 in the pregabalin group, significantly in favor of the capsaicin treatment. Treatment-emergent adverse events leading to permanent treatment discontinuation were only reported for pregabalin therapy.

One conclusion was that while pregabalin acts only on central sensitization, the superiority of the capsaicin may be due to its local ability to act on both central and peripheral sensitization.

This is the first study underlining the potential superiority of topical administration of analgesics over oral administration.


Cruccu G, Nurmikko TJ, Ernault E, Riaz FK, McBride WT, Haanpää M. Superiority of capsaicin 8% patch versus oral pregabalin on dynamic mechanical allodynia in patients with peripheral neuropathic pain. Eur J Pain. 2017 Dec 1. doi: 10.1002/ejp.1155.