Marsili Syndrome as a Gateway to Novel Analgesic Targets

Summary

Congenital insensitivity to pain (CIP) comprises a group of rare genetic disorders caused by mutations in genes essential for pain sensing in humans. Among these, Marsili syndrome is caused by a dominant point mutation in the transcription factor ZFHX2, and it is characterized by markedly reduced sensitivity to noxious heat, mechanical injury, while other functions remain intact. this project aims to establish the first integrated, system-level characterization of Marsili syndrome by combining human sensory phenotyping with neurophysiological and molecular analyses. The study will be conducted in two sessions of approximately 4 hours each, 24 hours apart from each other

Conditions

• Marsili Syndrome

Interventions

OTHER

Histamine

To deliver histamine, standard allergy skin prick test (SPT) lancets are applied

OTHER

Cowhage (Mucuna Pruriens)

The spicules will be manually inserted. Approximately 30-35 spicules are gently rubbed into a 1 cm diameter skin area on the forearm

DRUG

Capsaicin 8% Patch

Capsaicin patches (2x2 cm, dosage form: transdermal patch 8%) will be applied on the selected area. The patch will be left in place for 30 minutes after which it will be removed.

OTHER

Knee Injections of hypertonic saline

Experimental knee pain will be induced with a 0.25-0.30 mL bolus injection of 5% hypertonic saline, which will be injected into the dominant Infrapatellar Fat Pad (IFP)

OTHER

Cold Pressure Test

Participants will be asked to place their hand in the cold-water tank (temperature around 5°C) and to keep it for as long as they can tolerate it.

OTHER

Computerized Conditioned Pain Modulation (CPM)

CPM will be assessed using a double-cuff.

Sponsors & Collaborators

• Aalborg University

  lead OTHER

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-01

Primary Completion

2026-12-31

Completion

2027-12-31

Countries

• Denmark

Study Locations