Neuropeptides Substance P and CGRP Show Opposite Patterns in Two Types of Scarring Hair Loss
Substance P and CGRP neuropeptides were altered in scalp biopsies from patients with lichen planopilaris and frontal fibrosing alopecia, but in opposite directions — suggesting these similar-looking diseases have different underlying mechanisms.
Quick Facts
What This Study Found
Immunohistochemistry and confocal microscopy revealed altered expression of substance P and CGRP in both affected and unaffected scalp skin from LPP and FFA patients compared to controls. However, ELISA quantification showed opposite patterns in LPP versus FFA — suggesting different pathogenic mechanisms despite similar histopathological features. Notably, inflammation was present in clinically unaffected scalp skin in both diseases, indicating these may be more generalized scalp processes than previously thought.
Key Numbers
How They Did This
Scalp biopsies from patients with LPP, FFA, and healthy controls were analyzed using immunohistochemistry and confocal microscopy to visualize substance P and CGRP expression. ELISA was used to quantitatively compare neuropeptide levels between affected and unaffected scalp tissue across all three groups.
Why This Research Matters
FFA has reached epidemic levels in recent years with no clear cause identified. If neurogenic inflammation drives these scarring hair loss conditions, it opens the door to targeted treatments — potentially including drugs that block substance P or CGRP (some of which already exist for other conditions like migraines). Understanding the distinct mechanisms of LPP vs FFA is crucial for developing disease-specific therapies.
The Bigger Picture
Neurogenic inflammation — where nerve-derived peptides drive inflammatory processes — is increasingly recognized in skin diseases. The fact that CGRP-blocking drugs are already FDA-approved for migraines raises the intriguing possibility that similar approaches could be explored for scarring alopecia. This study provides mechanistic groundwork for that direction.
What This Study Doesn't Tell Us
This was a small study with scalp biopsies from a limited number of patients. The abstract does not specify exact sample sizes or the magnitude of neuropeptide differences. The opposite ELISA patterns are suggestive but need replication in larger cohorts. The study cannot determine whether neuropeptide changes cause the disease or are a consequence of it.
Questions This Raises
- ?Could CGRP-blocking migraine drugs (like erenumab) have therapeutic benefit in frontal fibrosing alopecia?
- ?What drives the opposite neuropeptide patterns in LPP versus FFA despite their histopathological similarity?
- ?Does the finding of subclinical inflammation in unaffected scalp mean earlier treatment could prevent progression of these diseases?
Trust & Context
- Key Stat:
- Opposite neuropeptide patterns LPP and FFA showed opposite substance P and CGRP expression despite looking similar histologically, suggesting different disease mechanisms
- Evidence Grade:
- This is a small translational study using human scalp biopsies with both qualitative (immunohistochemistry) and quantitative (ELISA) analysis. While it provides important mechanistic insight, the limited sample size and cross-sectional design prevent definitive conclusions about causation.
- Study Age:
- Published in 2020, this study was among the first to provide neuropeptide evidence for distinct pathogenic mechanisms in LPP versus FFA, during a period of rapidly growing interest in the FFA epidemic.
- Original Title:
- Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism.
- Published In:
- Experimental dermatology, 29(3), 282-285 (2020)
- Authors:
- Doche, Isabella, Wilcox, George L, Ericson, Marna, Valente, Neusa S, Romiti, Ricardo, McAdams, Brian D, Hordinsky, Maria K
- Database ID:
- RPEP-04775
Evidence Hierarchy
Frequently Asked Questions
What are substance P and CGRP, and how do they relate to hair loss?
Substance P and CGRP are signaling molecules released by nerve endings in the skin. When present in abnormal amounts, they can trigger inflammation — a process called neurogenic inflammation. In scarring hair loss conditions, this nerve-driven inflammation may contribute to the destruction of hair follicles.
Why is FFA considered an epidemic?
Frontal fibrosing alopecia has dramatically increased in prevalence over the past decade, particularly in postmenopausal women in Europe and the Americas. The cause of this increase is unknown, and environmental factors like sunscreen ingredients have been investigated but not confirmed. The rapid rise has alarmed dermatologists and researchers.
Read More on RethinkPeptides
Related articles coming soon.
Cite This Study
https://rethinkpeptides.com/research/RPEP-04775APA
Doche, Isabella; Wilcox, George L; Ericson, Marna; Valente, Neusa S; Romiti, Ricardo; McAdams, Brian D; Hordinsky, Maria K. (2020). Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism.. Experimental dermatology, 29(3), 282-285. https://doi.org/10.1111/exd.13835
MLA
Doche, Isabella, et al. "Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism.." Experimental dermatology, 2020. https://doi.org/10.1111/exd.13835
RethinkPeptides
RethinkPeptides Research Database. "Evidence for neurogenic inflammation in lichen planopilaris ..." RPEP-04775. Retrieved from https://rethinkpeptides.com/research/doche-2020-evidence-for-neurogenic-inflammation
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.