Pain Biomarker Study (PBS)

The Pain Biomarker Study: Changes in Circulating Pain Signalling Molecules With Activation of Pain Receptors

This study investigates molecular and physical biomarkers of headaches in order to better understand mechanisms of these diseases.

There are 3 main parts:

1. Use of capsaicin (active ingredient in hot chili peppers) to trigger release of calcitonin gene related peptide - the hypothesis is that this will be different in headache subjects compared to controls (and if so might be used to predict how these patients will respond to certain medications that modulate calcitonin gene-related peptide). Subjects will be given capsaicin as a cream applied to the forehead or the inner nostril, or a hot sauce that is ingested.
2. Use of capsaicin to trigger eye watering - the hypothesis is that oxygen gas will slow down the amount of eye watering. Cluster headache patients respond very powerfully to oxygen gas but to very little else. The mechanism for oxygen is unknown but in rodents there is data that it works on the parasympathetic / lacrimal gland system. This study translates rodent data into humans in a non-invasive way to confirm the mechanism of this very effective treatment.
3. Use of ice water to trigger headaches - brain freeze causes a very short-lived but intense headache that may cause similar biomarker release as other headache disorders. This may be a useful human model for other headache disorders.

Study Overview

• Status: Enrolling by invitation
• Conditions: Migraine; Cluster Headache; Trigeminal Autonomic Cephalgia; Hemicrania Continua; Paroxysmal Hemicrania; SUNCT; Short-Lasting Unilateral Neuralgiform Headache With Conjunctival Injection and Tearing
• Intervention / Treatment: Drug: Oral capsaicin; Other: Medical Air; Drug: Low Flow Oxygen; Drug: High Flow Oxygen; Drug: Topical capsaicin; Drug: Intranasal capsaicin; Other: Cold Water Irrigation

• Study Type: Interventional
• Enrollment (Estimated): 371
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Diagnosis of one of the following: a. Diagnosis of a primary headache disorder according to the International Headache Classification, including migraine with aura, migraine without aura, chronic migraine, tension headache, cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA), and hemicrania continua; b. Diagnosed by a pain medicine physician with lumbar radiculopathy (possibly including neuropathic features, nerve impingement on MRI, or electromyography (EMG) report suggestive of lumbar radiculopathy); or c. Healthy control subject with no history of debilitating headaches or debilitating back pain / radiculopathy pain, and no headaches or back pain within the previous 3 months.
• Able to provide HIPAA authorization to share prior medical records/imaging
• Age 18 and older

Exclusion Criteria:

• The following items exclude the subject from all portions of the study: a. Known history of cardiovascular or neurovascular diseases. These diseases may include carotid stenosis of >50%, vertebral stenosis, peripheral vascular disease, angina or myocardial infarction, stroke, or vascular malformations; b. History of brain tumors or epilepsy; c. Active pregnancy or lactation; d. Daily cigarette, tobacco or nicotine use; e. Life expectancy less than 1 year, co-existing disease or other characteristic that precludes appropriate diagnosis of headache or spine pain; f. Active drug / alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements; or g. Inability or unwillingness of subject to give informed consent (e.g., ward of the state)
• The following items exclude the subject only from the capsaicin portion of the study: a. Known allergy to capsaicin or hot peppers
• The following items exclude the subject only from the oxygen portion of the study: a. Pulmonary or other non-headache diseases that require the use of supplemental oxygen
• The following items exclude the subject only from the cold water irrigation (ice water) portion of the study: a. Trauma, fractures, or congenital abnormalities of the soft palate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral capsaicin	Drug: Oral capsaicin; Subjects will drink a solution with capsaicin
Sham Comparator: Oral capsaicin and Medical Air	Drug: Oral capsaicin; Subjects will drink a solution with capsaicin; Other: Medical Air; Subjects will be exposed to medical air
Experimental: Oral Capsaicin and Low Flow Oxygen	Drug: Oral capsaicin; Subjects will drink a solution with capsaicin; Drug: Low Flow Oxygen; Subjects will be exposed to oxygen gas between 1-9 L/min
Experimental: Oral capsaicin and High Flow Oxygen	Drug: Oral capsaicin; Subjects will drink a solution with capsaicin; Drug: High Flow Oxygen; Subjects will be exposed to oxygen gas between 10-25 L/min
Experimental: Topical capsaicin	Drug: Topical capsaicin; Capsaicin cream will be applied to the skin of the forehead, cheek, or leg
Sham Comparator: Topical capsaicin and Medical Air	Other: Medical Air; Subjects will be exposed to medical air; Drug: Topical capsaicin; Capsaicin cream will be applied to the skin of the forehead, cheek, or leg
Experimental: Topical capsaicin and Low Flow Oxygen	Drug: Low Flow Oxygen; Subjects will be exposed to oxygen gas between 1-9 L/min; Drug: Topical capsaicin; Capsaicin cream will be applied to the skin of the forehead, cheek, or leg
Experimental: Topical capsaicin and High Flow Oxygen	Drug: High Flow Oxygen; Subjects will be exposed to oxygen gas between 10-25 L/min; Drug: Topical capsaicin; Capsaicin cream will be applied to the skin of the forehead, cheek, or leg
Experimental: Intranasal capsaicin	Drug: Intranasal capsaicin; Capsaicin cream will be applied to the nostril
Sham Comparator: Intranasal capsaicin and Medical Air	Other: Medical Air; Subjects will be exposed to medical air; Drug: Intranasal capsaicin; Capsaicin cream will be applied to the nostril
Experimental: Intranasal capsaicin and Low Flow Oxygen	Drug: Low Flow Oxygen; Subjects will be exposed to oxygen gas between 1-9 L/min; Drug: Intranasal capsaicin; Capsaicin cream will be applied to the nostril
Experimental: Intranasal capsaicin and High Flow Oxygen	Drug: High Flow Oxygen; Subjects will be exposed to oxygen gas between 10-25 L/min; Drug: Intranasal capsaicin; Capsaicin cream will be applied to the nostril
Experimental: Cold water irrigation	Other: Cold Water Irrigation; Subjects will be asked to drink up to 2000 ml of cold water or ice water (temperature 0-10 degrees Celsius) as fast as possible, either continuously or intermittently (i.e. 200-800 ml at a time)
Sham Comparator: Cold water irrigation and Medical Air	Other: Medical Air; Subjects will be exposed to medical air; Other: Cold Water Irrigation; Subjects will be asked to drink up to 2000 ml of cold water or ice water (temperature 0-10 degrees Celsius) as fast as possible, either continuously or intermittently (i.e. 200-800 ml at a time)
Experimental: Cold water irrigation and Low Flow Oxygen	Drug: Low Flow Oxygen; Subjects will be exposed to oxygen gas between 1-9 L/min; Other: Cold Water Irrigation; Subjects will be asked to drink up to 2000 ml of cold water or ice water (temperature 0-10 degrees Celsius) as fast as possible, either continuously or intermittently (i.e. 200-800 ml at a time)
Experimental: Cold water irrigation and High Flow Oxygen	Drug: High Flow Oxygen; Subjects will be exposed to oxygen gas between 10-25 L/min; Other: Cold Water Irrigation; Subjects will be asked to drink up to 2000 ml of cold water or ice water (temperature 0-10 degrees Celsius) as fast as possible, either continuously or intermittently (i.e. 200-800 ml at a time)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activation of trigeminoautonomic reflex as assessed by change in Calcitonin gene-related peptide (CGRP) levels from before stimulation to after stimulation.		10 minutes before pain stimulation and 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by tear fluid production	The amount of tear fluid after each intervention will be measured via Schirmer strips	90 minutes after pain stimulation

Secondary Outcome Measures

Outcome Measure	Time Frame
Activation of trigeminoautonomic reflex as assessed by change in pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) levels levels from before stimulation to after stimulation.	10 minutes before pain stimulation and 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by saliva production	90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by nasal fluid production	90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by tactile threshold measurement with von Frey Filaments	90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by dermal blood flow	90 minutes after pain stimulation

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: University of California, San Francisco
• Investigators: Principal Investigator: Mark Burish, MD PhD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2018
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: April 26, 2018
• First Posted (Actual): April 30, 2018

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Capsaicin; Brain Freeze
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Lacerations; Cluster Headache; Trigeminal Autonomic Cephalalgias; Paroxysmal Hemicrania; Organic Chemicals; Heterocyclic Compounds; Fatty Acids; Lipids; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Hydrocarbons, Cyclic; Environment and Public Health; Alkaloids; Hydrocarbons, Aromatic; Amides; Catechols; Phenols; Benzene Derivatives; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Atmosphere; Meteorological Concepts; Fatty Acids, Unsaturated; Solanaceous Alkaloids; Polyunsaturated Alkamides; Fatty Acids, Monounsaturated; Capsaicin; Air
• Other Study ID Numbers: HSC-MS-17-0763

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No