The Effect of Remote Electrical Neuromodulation (REN) on Conditioned Pain Modulation (CPM) in Migraine and Fibromyalgia
A Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Effect of a REN Wearable Device on Conditioned Pain Modulation (CPM) in Patients With Migraine and/or Fibromyalgia
Who can join
Ages 18 and older · All sexes
Full eligibility criteria
Inclusion Criteria: \- Adults diagnosed with migraine and/or fibromyalgia above 18 years old. For migraine: * Has been diagnosed with migraine according to the ICHD-3 diagnostic criteria for migraine * Experiencing 6-24 headache days per month * Uses up to 1 prescribed preventive medication for migraine * Did not make any changes to their migraine medications treatment in the month prior to the study enrollment. For Fibromyalgia: * Has been diagnosed with FM according to the ACR 2010/6 diagnostic criteria for FM with disease duration for at least 6 months prior to study enrolment. * Did not make any changes to their FM medications in the month prior to the study enrollment. * Naïve to the Nerivio device. * Must be able and willing to comply with the protocol. * Provides written informed consent form. Exclusion Criteria: * Has an implanted electrical and/or neurostimulation device (e.g., cardiac pacemaker or defibrillator, vagus nerve neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator cochlear implant, sphenopalatine ganglion stimulator bladder stimulator, or occipital nerve stimulator). * Patients with severe depression. * Patients with known epilepsy. Use of any analgesics (OTC or prescribed) 24 hours prior to the study enrollment. * Use of Cannabis within 10 days prior to the study enrollment. * Use of opioids 2 months prior to the study enrollment. * Pregnant or breastfeeding
About the study
Migraine and Fibromyalgia (FM) are chronic pain disorders characterized by altered central pain processing and impaired endogenous pain inhibition. FM presents with widespread musculoskeletal pain, fatigue, sleep disturbance, and cognitive symptoms and is strongly associated with central sensitization. Migraine similarly involves dysfunction of central inhibitory and descending pain modulation, with evidence of abnormal cortical excitability, impaired sensory habituation, and alterations in pain-related evoked potentials.
Conditioned Pain Modulation (CPM) is a measure of the body's endogenous pain-inhibitory mechanism, based on the phenomenon whereby the pain evoked by one painful stimulus (the test stimulus) is reduced by the concurrent application of a second, remote nociceptive stimulus (the conditioning stimulus). It is widely regarded as a proxy for the function of descending pain-modulatory pathways.
CPM is used as an experimental biomarker of descending pain inhibition across chronic pain conditions, including fibromyalgia and migraine. Studies consistently demonstrate reduced inhibitory responses in both migraine and fibromyalgia compared with healthy controls, indicating a robust deficit in descending pain modulatory systems. Combining a contact heat test stimulus (TS) with a cold pressor conditioning stimulus (CS) is a widely used and validated CPM paradigm.
Nerivio, a Remote Electrical Neuromodulation (REN) device, is a non-invasive, non-pharmacological therapy indicated for the acute and preventive treatment of migraine. The REN device is worn on the upper arm and delivers peripheral electrical stimulation to activate CPM-related descending inhibitory pathways and reduce migraine pain. This distal stimulation approach is designed to activate CPM-related circuits by recruiting brainstem pain-regulatory centers and modulating central nociceptive processing.
This randomized, double-blind, placebo-controlled trial is designed to assess the effect of a single REN session on CPM and cortical pain processing in adults with migraine or fibromyalgia. Using a standardized CPM induction protocol, the study will evaluate changes in behavioral CPM responses, before, during, and after REN vs. sham stimulation in patients with migraine or fibromyalgia. This study aims to clarify whether REN enhances descending pain inhibition and pain processing in populations with impaired endogenous pain modulation.
What is being tested
- Remote Electrical Neuromodulation (REN) device (device)
Sponsor: Theranica · Participants: 120 · Started: Jun 23, 2026
Contact the study team
- Dagan Harris, PhD · Phone: +972723909763
- Yara Asmar, BSc · Phone: +972723909763
Official record on ClinicalTrials.gov — NCT07841509
Locations in the U.S.
| New Jersey | Theranica Bio-Electronics Inc, Bridgewater (Not yet recruiting) |
Conditions
From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.