Microneurographic testing of peripheral nerves in adults with PIEZO2-related sensory and proprioception problems and healthy volunteers

Microneurographic Assessment of Peripheral Nerves in Healthy Volunteers and Individuals With Sensory Dysfunction Caused by Inherited Mutations in the PIEZO2 Gene

Researchers will test whether tiny needle recordings from peripheral nerves show weaker responses to light touch and other sensations in adults with PIEZO2‑deficiency compared with healthy adults.

Quick facts

• Study type: Observational
• Enrollment: 16 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT06052631 on ClinicalTrials.gov

What this trial studies

This observational study uses microneurography to record electrical activity from peripheral sensory nerves in adults with genetically confirmed PIEZO2 loss-of-function and in healthy volunteers. Ultrasound will locate target nerves, and very thin recording electrodes will be inserted through the skin while investigators apply controlled stimuli including gentle brushing, mild electrical pulses, vibration, and thermal (heat and cold) tests. Participants will typically attend at least one clinic visit at the NIH Clinical Center where nerve responses such as firing rate and receptor subtype activity will be measured. Comparing responses between groups aims to determine which types of mechanically sensitive neurons are affected by PIEZO2 mutations and whether peripheral neurons remain otherwise healthy.

Who should consider this trial

Good fit: Ideal candidates are adults (18+) with genetically confirmed PIEZO2 loss-of-function enrolled in protocol 16-AT-0077, or healthy adults in good general health willing to undergo microneurography.

Not a fit: People with sensory loss from other causes (such as peripheral neuropathy), skin conditions that affect testing, limb amputation, or those unable to tolerate needle-based recordings are unlikely to benefit.

Why it matters

Potential benefit: If successful, the findings could explain how PIEZO2 mutations alter touch and proprioceptive signaling and help guide new diagnostic tests or targeted therapies.

How similar studies have performed: Microneurography is an established technique for recording human peripheral nerve activity and prior genetic and clinical work links PIEZO2 to touch and proprioception, but direct microneurographic characterization in PIEZO2 patients is novel.

Eligibility criteria

* INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

All Participants

* Stated willingness to comply with all study procedures and availability for the duration of the study
* Male or female, aged 18 years and over.
* The ability to provide written informed consent.
* Enrolled in 16-AT-0077, "Clinical and Scientific Assessment of Pain and Painful Disorders".

PDS Patients

-Clinical and genetic diagnosis of PIEZO2-LOF.

Healthy participants

-In good general health as evidenced by medical evaluation under 16-AT-0077.

EXCLUSION CRITERIA:

All Participants:

* Difficulties with communication that make subjective innocuous and pain assessments impossible or unreliable.
* Unable to comply with study procedures or visits.
* Has a dermatological condition that might influence cutaneous sensitivity.
* Congenital limb deficiency or amputation of any limb.
* Prior history of syncope.
* Peripheral neuropathy or current chronic pain condition or has had chronic pain in the past year (painful condition lasting more than six months), including ongoing treatment with medications for neuropathic pain (e.g. gabapentin, tricyclic antidepressants, pregabalin, tramadol).
* Has a major medical condition, such as kidney, liver, cardiovascular, autonomic, pulmonary, or neurological problems (e.g., epilepsy) or a chronic systemic disease (e.g., diabetes), or Raynaud's Disease.
* Current and untreated diagnosis of depression, post-traumatic stress, syndrome, bipolar disorder, psychosis, anxiety or panic disorder, alcohol or substance use disorders.
* Pregnant (verbal confirmation) or breastfeeding.
* Are participating in other ongoing research protocols involving interventions that would interfere with somatosensation.
* Employees or staff that work at NCCIH.
* Adults who are unable to provide their own consent.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Miroslav Backonja, M.D. — National Center for Complementary and Integrative Health (NCCIH)
• Study coordinator: Hayley M Hansen

Conditions PIEZO2-Deficiency Syndrome; Sensation; TOUCH; Proprioception