The Effect of Remote Electrical Neuromodulation (REN) on Conditioned Pain Modulation (CPM) in Migraine and Fibromyalgia

Condition(s) studied

Investigational drug(s) / intervention(s)

Remote Electrical Neuromodulation (REN) device: Nerivio is a Remote Electrical Neuromodulation (REN) Device. It is approved for the acute and/or preventive treatment of migraine from the age of 8 and above.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Between-groups (Active vs Placebo) difference in mean change of Conditioned Pain Modulation (CPM) activity from post-treatment (CPM4) to baseline (CPM1), measured by Numeric Rating Scale (NRS, 0-10). — 1 hour
  Difference between the Active and Placebo groups in the mean change of pain levels following Test Stimulus (TS) at 15 minutes post-treatment with the REN wearable as the Conditioned Stimulus (CS) versus pain levels following Test Stimulus (TS) under cold water as Conditioned Stimulus (CS): (CPM4 REN - CPM1 REN) - (CPM4 Placebo - CPM1 Placebo) = (P5 REN - P2 REN) - (P5 Placebo - P2 Placebo) The pain range is between 0 to 10. CPM4 is the difference between the pain level with REN as CS and pain prior treatment without Conditioned Stimulus (CS). CPM1 is the difference between the pain level with Cold Water as Conditioned Stimulus (CS) and pain prior treatment without Conditioned Stimulus (CS). Thus, the expected value is a negative number and higher number means higher CPM activity.

Trial sites (2)

More Theranica trials in the USA

Other trials for the same condition