rethinkPeptides Search
Menu
Study breakdown

Pregabalin May Control Itch in Prurigo Nodularis by Suppressing Substance P and CGRP Release

evidence
The takeaway

A patient's itch from prurigo nodularis returned after stopping pregabalin and resolved again when it was restarted, suggesting the drug may work by suppressing neuropeptide release including substance P and CGRP.

Itch recurred within 2 months

Pruritus returned after pregabalin was stopped and resolved again within 2 months of restarting, despite no visible skin lesions

What the researchers found

A 69-year-old woman with prurigo nodularis achieved complete skin lesion resolution with nemolizumab. Discontinuation of pregabalin (prescribed for coexisting sciatic pain) led to pruritus recurrence within 2 months despite continued absence of visible lesions. Reintroduction of low-dose pregabalin stabilized symptoms within 2 months. The proposed mechanism is pregabalin's inhibition of α2δ voltage-gated calcium channel subunits, suppressing release of excitatory neuropeptides including substance P and CGRP.

Why it matters

Prurigo nodularis causes debilitating itch that severely impacts quality of life. While new biologics like nemolizumab clear skin lesions, some patients continue to experience neuropathic itch. Understanding that pregabalin may address this residual itch through neuropeptide suppression could provide an affordable adjunctive treatment, especially since pregabalin is already widely available and inexpensive as a generic.

How the study worked

Single-patient case report documenting the temporal relationship between pregabalin use/discontinuation/reintroduction and pruritus control in a patient with prurigo nodularis concurrently treated with nemolizumab.

What this study cannot tell us

This is a single case report, the lowest level of clinical evidence. The temporal association between pregabalin and itch control is suggestive but cannot prove causation. The patient was concurrently on nemolizumab, making it difficult to fully attribute effects to pregabalin. Placebo effects cannot be excluded. No itch severity scoring was reported.

How to read the evidence

This is a single case report providing anecdotal evidence for pregabalin's antipruritic effect. While the on-off-on pattern is suggestive, it cannot establish causation or generalizability without controlled studies.

When this study was published

Published in 2025, this case report reflects current interest in addressing the neuropathic component of chronic itch conditions using existing medications.

The bigger picture

The recognition that chronic itch can have a neuropathic component — driven by aberrant neuropeptide signaling (substance P, CGRP) — is changing how dermatologists approach treatment. Pregabalin, already used for neuropathic pain, may bridge the gap between dermatological and neurological approaches to itch, particularly for patients who don't fully respond to skin-targeted therapies alone.

Questions still open

  • Would a controlled trial of pregabalin as adjunct therapy for prurigo nodularis confirm this observation?
  • Is the neuropathic itch component (driven by substance P and CGRP) a distinct phenotype within prurigo nodularis that predicts response to pregabalin?
  • Could combining pregabalin with CGRP-blocking antibodies provide synergistic anti-itch effects?

Common questions

How might pregabalin reduce itch if it's a pain medication?
Pregabalin works by blocking calcium channels on nerve endings, which reduces the release of signaling molecules like substance P and CGRP. These same neuropeptides are involved in both pain and itch signaling, which is why a pain drug can also help with itch — especially when the itch has a nerve-based (neuropathic) component.
What is prurigo nodularis and why is it so hard to treat?
Prurigo nodularis is a chronic skin condition causing intensely itchy, hard nodules. The itch-scratch cycle makes it worse, and the itch can persist even after skin lesions clear because nerve fibers in the skin become sensitized. This neuropathic component is why standard skin treatments alone may not fully control symptoms.

Read the original research

Pregabalin as a Potential Adjunct in the Management of Pruritus in Prurigo Nodularis: A Case Report.

Cureus, 17(7), e88297

Citation

Mima, Yoshihito; Yamamoto, Masako; Iozumi, Ken. (2025). Pregabalin as a Potential Adjunct in the Management of Pruritus in Prurigo Nodularis: A Case Report.. Cureus, 17(7), e88297. https://doi.org/10.7759/cureus.88297