Arman Yurisaldi Saleh, NIM011317017333 (2016) Perubahan Kadar Nitrit Oksida Ekshalasi Endogen dan Visual Analog Scale (VAS)pada Pasien Migren dengan Neuromuscular Electrical Stimulation (NMES)Uji Klinis Buta Ganda Terandomisasi. Disertasi thesis, UNIVERSITAS AIRLANGGA.

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Abstract

Introduction: Migraine is a public health problem that has a huge impact on patients and their families. The patients undergo neurochemical changes in the duramater, which increase levels of Nitric Oxide (NO) as a result of excessive activity of inducible-Nitric Oxide Synthase (i-NOS) during acute migraine attacks (ictal). Some researchers assume NO as a cause of headache in migraine. Oral abortive pharmacological therapy for acute migraine attacks, experiences absorption barriers due to the increased of sympathetic nerve activity in the gut. Therefore the therapeutic effect is not immediate benefits. In migraine sufferers found endocannabinoid deficiency, that function as a brain's natural analgesic. Endocannabinoid is known to suppress inflammatory processes in the trigeminal ganglion through the decrease activity of CGRP, serotonin etc. Increased levels of endocannabinoid in migraine may occur due to an increase activity of endogenous neuronal-NOS (n-NOS) from the cerebellum. This n-NOS is secreted synergically in the process of Long-Term Depression (LTD), which can suppress the activity of CGRP that ultimately can reduce pain in migraine. Increased levels of the n-NOS can be achieved through Neuromuscular Electrical Stimulation (NMES) of the cerebellum. This study used NMES which is based on the fact that NO is a modulator of various neurotransmitters and natural analgesic in the brain, including endocannabinoids. The NMES procedure was carried out through the stimulation of median nerve (fast conduction type II and III). This stimulation will raise the activity of the cerebellum in the event of a muscle twitch. Aim: The aim of this study was to get a migraine abortive therapy through the use of NMES with a combination of electrical amplitude and frequency appropriately. Methods: This study was carried out through 3 phases, as follows: 1. Measurements of endogenous nitric oxide exhalation conducted in 91 subjects consisting of 30 normal subjects, 31 subjects without migraine attacks (interictal) and 30 subjects with migraine attacks (ictal). 2. Study phase 2 was to find a combination of electrical amplitude and frequency of NMES appropriately, so that the subjects feel comfortable without pain. 3. The subjects who fulfilled the International Headache Society (IHS) criteria, including migraine with and/or without aura, were randomized into clinical trial group (n=33) and sham group (n=30). The NMES was performed with blinding to the subjects, using 6 mA, 125 Hz and 0.2 ms. Endogenous exhalated NO levels and clinical improvements using Visual Analog Scale (VAS), were measured before and after NMES treatment. Results: 1. The levels of endogenous exhalated NO in each group were: normal group (median=5), interictal group (median=11), ictal group (median=14). Coefficient correlation between VAS and endogenous exhalated NO level, was 0.815. 2. The combination of amplitude of 6 mA, and frequency of 125 Hz was the best result for subjects. This combination was able to decrease pain intensity and decrease endogenous exhalated NO level during migraine attack. 3. There was a significant difference of pain intensity and endogenous exhalated NO level between sham group + paracetamol compared to clinical trial group + paracetamol, before and after NMES treatment. Conclusion: NMES with a combination of amplitude of 6 mA, and frequency of 125 Hz can be used as a migraine abortive therapy.

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