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REN* – Remote Electrical Neuromodulation
Remote Electrical Neuromodulation (REN*) is an innovative, non-invasive, non-pharmacological technology for the treatment of pain and other symptoms associated with migraines.
Individual neuromodulation using the REN* method
The basic principle behind REN* is conditioned pain modulation (CPM). This refers to an endogenous, pain-inhibiting mechanism. It is based on the fact that a conditioned stimulus inhibits pain in a distant region of the body [1].
This mechanism is caused by peripheral nociceptive neuronal activity that ascends via spinal neurons to the pain processing centers in the brainstem (red arrow). In the case of REN* application with Nerivio®, the bracelet worn on the upper arm sends non-painful electrical stimuli (black arrow) along the ascending somatosensory pathway, the so-called anterolateral system (C and Aδ fibers).
Reaching the signals in the brainstem activates the rostral ventromedial medulla and the periaqueductal gray (PAG) [2]. Descending inhibitory signals (green arrow) are then sent to the dorsal horn of the spinal cord and to the trigemino-cervical complex (TCC) to inhibit incoming nociceptive stimuli.
The pain-relieving effect in the trigeminal CC and trigeminal nerve is mediated by the release of norepinephrine into the cerebrospinal fluid and of serotonin (5-hydroxytryptamine, 5-HT) into the dorsal horn of the spinal cord [3].
This allows the overall result of the CPM mechanism to be effective remotely. It contributes to the nociceptive stimulation in the upper arm leading to the inhibition of migraine pain in the head [4]. With REN, users experience pain relief or freedom from migraine headaches as well as associated symptoms such as nausea, photophobia or phonophobia. [5].
Sources:
[1] Nir RR, Yarnitsky D. Conditioned pain modulation. Curr Opin Support Palliat Care 2015;9:131–137
[2] Sandkuhler J, Fu QG, Zimmermann M. Spinal pathways mediating tonic or stimulation-produced descending inhibition from the periaqueductal gray of nucleus raphe magnus are separate in the cat. J Neurophysiology 1987;58:327–41.
[3] Millan MJ. Descending control of pain. Prog Neurobiology 2002;66:355–474.
[4] De Tommaso M, Difruscolo O, Sardaro M, Libro G, Pecoraro C, Serpino C, Lamberti P, Livrea P. Effects of remote cutaneous pain on trigeminal laser-evoked potentials in migraine patients. Journal of Headache Pain 2007;8:167–174
[5] Yarnitsky D et al. Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Headache 2019;59:1240–1252
Electrical stimulation – the details
The electrodes of the Nerivio® wearable are attached to the outer part of the patient's upper arm using a bracelet.
The choice of arm does not matter and is independent of the side of the pain. Each treatment lasts 45 minutes. During the treatment, the wearable emits electrical impulses via electrodes attached to the skin.
Users control the intensity of the electrical impulses via a mobile application (app) on their smartphone. The app helps the user to adjust the intensity so that the stimulation is pleasant without causing pain.
Nerivio® – neuromodulation over the upper arm
REN* is based on descending pain inhibition, which occurs via conditioned pain modulation (CPM). CPM can be activated using the app-controlled Nerivio® neuromodulation band attached to the upper arm. The effects of CPM have been shown to be systemic, meaning that modulatory pathways through the lower brainstem inhibit or promote nociceptive processing throughout the body [5].
It was also determined that the location of the conditioning stimulus must be far enough away from the location of the conditioned pain. So if the conditioned pain is a headache, the conditioning stimulus should not be applied to the head.
