Nasal Surgery Relieved Headaches but Neuropeptide Levels Were Not the Cause | Research

The takeaway

Surgery to correct nasal contact points significantly reduced headaches at 3 and 12 months, but substance P, neurokinin A, and CGRP levels did not differ between contact and non-contact nasal tissue.

p<0.001 for headache relief
Surgery significantly reduced headache scores at 3 and 12 months, but all three neuropeptide comparisons between contact and non-contact tissue were non-significant (p>0.5).

What the researchers found

In 20 patients with secondary headaches and nasal contact points, surgery produced significant headache reduction measured by visual analog scale at 3 months (p<0.001) and 12 months (p<0.001) postoperatively.

However, fluorescein staining for substance P (p=0.631), neurokinin A (p=0.546), and CGRP (p=0.683) showed no statistically significant differences between contact mucosa and non-contact mucosa. This dissociation between clinical improvement and neuropeptide levels suggests the mechanism of headache relief from surgery involves factors other than local neuropeptide accumulation.

Why it matters

The relationship between nasal contact points and headaches has been debated for years. While this study confirms that surgery helps, it challenges the hypothesis that local neuropeptide accumulation at contact points drives the pain. This redirects researchers toward other mechanisms — such as mechanical pressure on trigeminal nerve endings — and helps set realistic expectations about neuropeptide-targeted nasal therapies.

How the study worked

This prospective study enrolled 20 adults with secondary headaches and nasal obstruction confirmed by endoscopy and CT scan. During corrective surgery, tissue samples were collected from both nasal contact points and non-contact areas. Neuropeptide intensity was measured using fluorescein-labeled antibodies against substance P, neurokinin A, and CGRP, analyzed with ImageJ software. Headache severity was assessed preoperatively and at 3 and 12 months post-surgery using a visual analog scale.

What this study cannot tell us

The study had only 20 patients with no non-surgical control group, making it impossible to account for placebo effects of surgery. Neuropeptide levels were measured by immunofluorescence intensity rather than quantitative assays like ELISA, which may lack sensitivity. The study only measured neuropeptide presence in tissue, not release or dynamic changes during headache episodes. Follow-up was limited to 12 months.

How to read the evidence

This is a small prospective study (n=20) without a control group. While the surgical outcomes are statistically significant, the lack of blinding and small sample size for neuropeptide analysis limit confidence in the negative peptide findings.

When this study was published

Published in 2016, this study predates the anti-CGRP antibody era in migraine treatment. The distinction between CGRP's role in primary migraine versus contact-point headaches has become more clinically relevant since then.

The bigger picture

CGRP and substance P are central to migraine biology, with anti-CGRP antibodies now widely used for migraine prevention. This study examines whether these same neuropeptides play a role in contact-point headaches — a distinct condition. The negative finding for local neuropeptide involvement helps differentiate the pathophysiology of contact-point headaches from primary migraines, where CGRP's role is well established.

Questions still open

If neuropeptides aren't elevated at contact points, what mechanism causes the headache — direct mechanical stimulation of trigeminal nerve endings?
Would more sensitive quantitative assays (like mass spectrometry) detect neuropeptide differences that immunofluorescence missed?
Could neuropeptide release during headache episodes differ even though baseline tissue levels are similar?

Common questions

What are nasal contact point headaches?

Nasal contact point headaches occur when structures inside the nose — like the septum and turbinates — press against each other. This mechanical pressure is thought to trigger headaches through nerve stimulation. Surgery to separate these contact points can relieve the headaches, though the exact mechanism is debated.

Why did the researchers expect to find elevated neuropeptides at contact points?

Substance P and CGRP are known pain-signaling molecules released by sensory nerves. Researchers hypothesized that the mechanical pressure at nasal contact points might cause local nerve irritation and increased neuropeptide release, driving headache pain. However, the tissue levels of these peptides were the same in contact and non-contact areas, suggesting other mechanisms are responsible.

Read the original research

An Analysis of Neuropeptides at Nasal Contact Points of Patients With Secondary Headache.

The Journal of craniofacial surgery, 27(3), e305-9

View on PubMed ↗Publisher’s paper ↗

Citation

Demir, Deniz; Cengiz, Nureddin; Güven, Mehmet; Bulduk, Oğuzhan. (2016). An Analysis of Neuropeptides at Nasal Contact Points of Patients With Secondary Headache.. The Journal of craniofacial surgery, 27(3), e305-9. https://doi.org/10.1097/SCS.0000000000002553