Rosacea: a complex dermatosis and the role of neurogenic inflammation

Rosacea is a chronic inflammatory skin condition affecting the central face, characterized by flushing, persistent erythema, papules, pustules, and telangiectasia [1]. Many patients also experience burning, stinging, and increased skin sensitivity [2]. The condition affects approximately 5.1% of the global population and can significantly impact quality of life [3].

The pathogenesis of rosacea is multifactorial, involving genetic predisposition, ultraviolet radiation, microorganisms (including Demodex), and oxidative stress. These factors trigger vascular and inflammatory responses.

In recent years, neurogenic inflammation has emerged as a key mechanism. Cutaneous sensory nerve endings, activated by triggers such as temperature changes, UV exposure, alcohol, and spicy food, release neuropeptides including substance P (SP) and calcitonin gene-related peptide (CGRP). These mediators induce vasodilation and activate mast cells, creating a self-amplifying inflammatory loop [4, 5].

A central role in this process is played by TRPV1 and TRPA1 receptors — “irritation sensors” located on sensory nerve endings. Their activation increases Ca²⁺ influx into neurons, triggers neural signaling, and promotes inflammatory responses. In rosacea, these receptors are overexpressed and hyperactive [1].

GABA and its derivatives: from neurotransmission to therapy

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system, regulating neuronal excitability and signal transmission [1].

GABA derivatives — gabapentin and pregabalin — are structurally related to GABA but act differently. They bind to the α2δ subunit of voltage-gated calcium channels in neurons, reducing Ca²⁺ influx and decreasing the release of excitatory mediators such as glutamate and substance P [1].

Gabapentin and pregabalin exert systemic effects on neuronal calcium channels, reducing the excitability of both central and peripheral neurons. This leads to suppression of neurogenic inflammation, which is expressed in the skin.

Additionally, these agents reduce the activity of TRPV1 and TRPA1 channels, thereby decreasing skin hypersensitivity and symptom severity.

Systemic therapy and clinical effects

These medications are administered orally and act systemically.

The following dosing regimens were used in clinical studies:

• gabapentin — 200–400 mg three times daily;
• gabapentin — 300 mg three times daily;
• pregabalin — from 150 mg/day up to 300 mg in the morning and 225 mg in the evening [1].

Clinical evidence suggests that GABA derivatives can reduce redness, flushing, and burning sensations. In one study, improvement was observed in 82.3% of patients with neurogenic rosacea [2].

Randomized trials have shown that gabapentin improves flushing and may also benefit associated symptoms such as sleep disturbances and migraine [1].

Safety, limitations, and practical relevance

GABA derivatives are generally well tolerated. The most commonly reported adverse effects are dizziness and somnolence [1].

It is important to note that the use of gabapentin and pregabalin in rosacea is off-label. Prescription of these medications is the responsibility of a physician, primarily a dermatologist, who determines the treatment strategy. In cases with pronounced neurosensory symptoms (burning, pain, hypersensitivity) or comorbid conditions, co-management with a neurologist may be appropriate [1]. A detailed list of contraindications should be consulted in the official prescribing information.

For skincare specialists, these findings are clinically relevant. They help to:

1. better understand the mechanisms behind rosacea symptoms,
2. explain why topical care alone may be insufficient in some cases,
3. and appropriately refer patients to a physician for further evaluation and treatment options.

Referencs

1. Li D., Yang W., Chen N., Xu Y. Updates in the treatment of rosacea with γ-aminobutyric acid derivatives. Clin Cosmet Investig Dermatol 2025; 18: 2207–2214. doi:10.2147/CCID.S546287
2. Kim H.O. ,Kang S.Y., Kim K.E. et al. Neurogenic rosacea in Korea. J Dermatol 2021; 48(1): 49–55.
3. Saurat J.H., Halioua B., Baissac C. et al. Epidemiology of acne and rosacea: a worldwide global study. J Am Acad Dermatol 2024; 90(5): 1016–1018.
4. Marek-Jozefowicz L., Nedoszytko B., Grochocka M. et al. Molecular mechanisms of neurogenic inflammation of the skin. Int J Mol Sci 2023; 24(5): 5001.
5. Wienholtz N.K.F., Christensen C.E., Ashina H. et al. Elevated plasma levels of calcitonin gene-related peptide in individuals with rosacea: a cross-sectional case-control study. J Eur Acad Dermatol Venereol 2025; 39(1): 181–188.