Repetitive transcranial magnetic stimulation of the prefrontal cortex for fibromyalgia syndrome: a randomised controlled trial with 6-months follow up

Abstract Objectives Fibromyalgia Syndrome (FMS), is a chronic pain disorder with poorly understood pathophysiology. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been recommended for pain relief in various chronic pain disorders. The objective of the present research was to study the effect of low frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) on pain status in FMS. Methods Ninety diagnosed cases of FMS were randomized into Sham-rTMS and Real-rTMS groups. Real rTMS (1 Hz/1200 pulses/8 trains/90% resting motor threshold) was delivered over the right DLPFC for 5 consecutive days/week for 4 weeks. Pain was assessed by subjective and objective methods along with oxidative stress markers. Patients were followed up for 6 months (post-rTMS;15 days, 3 months and 6 months). Results In Real-rTMS group, average pain ratings and associated symptoms showed significant improvement post rTMS. The beneficial effects of rTMS lasted up to 6 months in the follow-up phase. In Sham-rTMS group, no significant change in pain ratings was observed. Conclusion Right DLPFC rTMS can significantly reduce pain and associated symptoms of FMS probably through targeting spinal pain circuits and top-down pain modulation . Trial registration: Ref No: CTRI/2013/12/004228.(AU)

Repetitive transcranial magnetic stimulation in chronic tension-type headache: A pilot study

Background & objectives: Tension-type headache (TTH) is the most common type of primary headache disorder. Its chronic form is often the most ignored and challenging to treat. Transcranial magnetic stimulation (TMS) is a novel technique in the treatment of chronic pain. The aim of this pilot study was to explore the effect of low-frequency repetitive TMS (rTMS) on pain status in chronic TTH (CTTH) by subjective and objective pain assessment. Methods: Patients (n=30) diagnosed with CTTH were randomized into rTMS (n=15) and placebo (n=15) groups in this study. Pre-intervention detailed history of patients was taken. Numerical Rating Scale (NRS) for Pain and questionnaires [Headache Impact Test-6 (HIT-6), McGill Pain Questionnaire, Pain Beliefs Questionnaire, Coping Strategies Questionnaire, State-Trait Anxiety Inventory Test, Hamilton Rating Scale for Depression and WHO-Quality of Life Questionnaire-Brief version] were filled, and objective assessments such as nociceptive flexion reflex (NFR) and conditioned pain modulation were done. The tests were repeated after 20 sessions (5 days/week). In the rTMS group, 1200 pulses in eight trains of 150 pulses each were given at 1Hz over the right dorsolateral prefrontal cortex (RDLPFC). In the placebo group, the rTMS coil was placed such that magnetic stimulation did not reach the cortex. Results: The NRS score decreased significantly (P<0.001) and NFR thresholds increased significantly (P=0.011) in the rTMS group when compared to placebo group. Interpretation & conclusions: Subjective improvements in the NRS, HIT-6, McGill Present Pain Intensity, trait of anxiety and psychological pain beliefs were observed. The increase in the thresholds of NFR served as an objective marker for improvement in pain status. Further studies need to be done to confirm our preliminary findings.

Estimated features from surface EMG of the lower limb correlate with the subjective sensation of pain

Pain assessment is very important in establishing the efficacy of analgesics and therapies, but because pain is a subjective experience, using methods that represent pain objectively is necessary. A number of biopotentials have been employed in studies of the objective assessment of pain. However, few investigations have considered the peripheral nervous system response to electrical stimulation. The present study evaluated a method for pain quantification based on the analysis of biopotentials. We assessed electromyographic activity that resulted from evoked movements from the nociceptive flexion reflex (NFR). We investigated correlations between stimulus intensity, features extracted from surface electromyography (EMG), and subjective pain reported by subjects using a Visual Analog Scale (VAS). A total of 10 healthy male subjects without any pain disorder, aged 20-27 years, participated in the study. A high correlation (r2 > .87) was found between stimulus intensity and the following features extracted from the EMG: area, root mean square (RMS), and entropy. A high correlation (r2 > .99) was also found between stimulus intensity and subjective pain reported on the VAS. We conclude that estimating features from electromyographic signals that are correlated with subjective pain sensations and the intensity of the electrical stimulus is possible. Entropy, RMS, and the area of the electromyographic signal appear to be relevant parameters in correlations with subjective pain.

Interlimb Interaction at Different Angular Velocity in Isokinetic Knee Evaluation

OBJECTIVE: To investigate the influence of angular velocity on the interlimb interaction induced by movement patterns. METHOD: Sixty healthy adult men performed five maximal isokinetic knee extension-flexion contractions in each of two contralateral leg stabilization conditions at different angular velocities. In the "Front condition", the test was done with a bar in front of the ankle joint of the non-testing leg. In the Fix condition", the non-testing leg was strapped and induced reciprocally to perform isometric contractions with respect to the testing leg. From the measured values, we calculated the strength difference ratio ([Peak Torque (PT) of "Fix condition"-PT of "Front condition"x100/PT of "Front condition") at each angular velocity. RESULT: By comparing the extensor strength, greater PTs were measured at the "Fix condition" in all tested angular velocities (p<0.01). For the flexor, the PTs of both conditions were similar. The strength difference ratio decreased as angular velocity increased (r=-0.48, p<0.01) in the extensor. CONCLUSION: We could infer the crossed extension-flexion reflex is more apparent in the lower angular velocity than in higher one.

Suppressive effects on human flexion reflex induced by different pressure intensities and stimulation sites / 全日本鍼灸学会雑誌

Different intensities of pressure were applied to various tender or non-tender points and the suppressive effects on the flexion reflex were examined in 21 healthy humans (18-26 years), who gave informed consent. The sural nerve was stimulated transcutaneously with trains of 5 pulses at intervals of 13 sec (1.05-1.10x T, T : threshold) and evoked EMGs were recorded from the biceps femoralis muscle. Tender points in the contralateral forearm were detected by careful palpation, and conditioning pressure stimulation was applied at variousintensities by a push-pull gauge for 78 sec. Pressure applied to tender points induced slightly greater suppression of evoked EMGs than that to non-tender points (C statistics : time series analysis), although the difference was not significant (group comparison). Pressure intensities of ten and 50 % of pain tolerance pressure seemed to be adequate for suppression of EMGs in both tender and non-tender points. These results suggest that suppression of flexion reflex by pressure application in humans may be mediated by tactile and pain-related afferent fibers and the importance of adequate stimulus intensity for the induction of analgesic effects.

Effects of thermal stimulation on the flexion reflex in human subjects / 全日本鍼灸学会雑誌

Effect of thermal stimulation on the flexion reflex as a pain index was examined in healthy human subjects who gave informed consent (n=9, male, mean age 26 ± 8 years old). The evoked electromyogram (EMG) of biceps femoral muscle elicited by transcutaneous electrical stimulation of the sural nerve (5 trains of pulses at 100 Hz delivered at intervals of 13 sec) was successively recorded. The subjective pain sensation elicited by nerve stimulation was simultaneously recorded by the visual analogue scale (VAS) method. Significant correlation coefficients between the amplitudes of evoked EMGs and the stimulus intensity (r=0.791, P< 0.01), and the VAS value (r=0.724, P < 0.01) were observed. Conditioning hot water immersion of the hand (47 °C, 156s) tended to reduce the amplitudes of evoked EMGs, although change was not significant (P=0.678, Kruskal-Wallis test). However, C-statistics, a simple time series analysis method, demonstrated significant trends in several trials. These results suggest that the flexion reflex used in the present study is useful for pain research in human subjects and C-statistics are also useful for analyzing the effect on each individual.

The Inhibition of Ipsilateral and Contralateral VFR by Topical Cooling and Acupuncture of the Palmar Vibratory Site on One Side / 日本温泉気候物理医学会雑誌

Topical cooling effects at the site of vibratory stimulation were studied using vibration-induced flexion reflex (VFR), which was induced simultaneously in both hands, as an indicator for assessment.<br>As a result, it was found that the inhibition of ipsilateral and contralateral VFR related to topical cooling of the palmar vibratory site on one side was caused by cooling within a limited area of the palm where the vibratory element contacted. Application of acupunctural electrical stimulation of disrupting nature in place of topical cooling to the vibratory stimulation site on one side also effectively inhibited VFR on both sides.<br>Although the skin temperature did not decrease on the side contralateral to the side that had been cooled, VFR was completely inhibited on both the cooled and uncooled sides.<br>These results suggest that the peripheral impulses which arise from cooling the vibratory site on one side act on spinal interneurons and alpha-motor neurons, which contribute bilaterally to the VFR expression, thus inducing a neurogenic inhibitory effect on VFR.

Effects of Acupuncture Stimulation of Combination of Meridian Points on the Exteroceptive Vibration-Induced Finger Flexion Reflex / 全日本鍼灸学会雑誌

It is said that the key to effective acupuncture is to perform appropriate stimulation of the best combinations of meridian points which directly or indirectly affect the disease.<br>In order to determine the difference in the efficacy between combinations of clinically important meridian points, this study examined the effect of two-point acupuncture stimulation on the exteroceptive vibration-induced finger flexion reflex (Eklund et al., 1978).<br>METHOD<br>Subjects were six healthy adults of both sexes between 20 and 35 years of age. Two-point combinations were made of IC₄ Hegu (standard point) with each of the following points: IC₆ Pianli, P₇ Lieque, C₃ Shaohai, TM₂₀ Baihui, VU₁₃ Feishu, VU₂₅ Dachangshu, G₃₆ Zusanli. Perception threshold electrical stimulation of each combination was performed at 45Hz for 5min. using subcutaneous needles. The finger flexion reflex was induced by a tapping vibrator applied to the palm and recorded through a pressure transducer.<br>RESULTS<br>1) The combination of adjacent points on the hand: Stimulation of Hegu together with Pianli, both of which are on the Large Intestine meridian, caused a strong inhibition of the reflex. The inhibition lasted about twice as long as that caused by stimulation of Hegu alone. However, neither Hegu and Lieque not Hegu and Shaohai stimulation caused prolongation of the inhibition.<br>2) The combination of the hand and the back: Neither Hegu and Feishu nor Hegu and Dachangshu stimulation caused any prolongation of the inhibition.<br>3) The combination of the hand and the leg: Hegu and Zusanli stimulation caused marked inhibition, which lasted about four times as long as that caused by Hegu-alone stimulation.<br>4) The combination of the hand and the head: Hegu and Baihui stimulation caused no or much less inhibition that caused by Hegu-alone stimulation.<br>5) Examination of difference among stimulating methods: Electrical stimulation through surface electrodes (A), Retained subcutaneous needles (B), Electrical stimulation between a subcutaneous needle and the indifferent electrode. (C), Electrical stimulation between subcutaneous needles (D). The intensity of the inhibition effect of these methods can be expressed as follows:<br>D>C>B>A<br>DISCUSSION and CONCLUSION<br>The reflex inhibition caused by the standard point stimulation was strengthened or weakened by simultaneous stimulation of an additional point. Based on our examination of the characteristics of the inhibition, it was thought that not only mutual interference of impulses at the spinal level but also humoral factors and some polysynaptic reflex mechanism in the higher center level participate in this effect.

THE FLEXION REFLEX POTENTIAL AND DORSAL ROOT POTENTIAL INDUCED BY STIMULATION OF THE CUTANEOUS NERVE IN THE RAT / 西安交通大学学报(医学版)

On the intact and awake rat, the flexion reflex potential (FRP)and dorsal root potential (DRP) induced by stimulation of the cutaneous nerve with graded intensity stimulations to the sural nerve (a pure cutaneous nerve) were observed, there appeared A-FRP and C-FRP one after the other on the hamstring nerve (a group of nerves innervating the hindlimb flexors), and A-DRP and C-DRP on the L_5 dorsal root at the same time. The threshold and the latencices of A-FRP and A-DRP had no differences, and had significant positive correlations. The amplitudes of A-FRP and A-DRP increased simultaneously with the increase of the stimulating intensity in certain range. The threshold and latency of C-FRP are larger than those of C-DRP. The threshold and the latency of the C-FRP and C-DRP showed significant positive correlation. The amplitudes of C-FRP and C-DRP increased simultaniously with the increase of the stimulating intensity in certain range. The train stimuli (three pulses, 5ms interval, 0. 5ms duration) induced larger FRP and DRP than those induced by single stimulus. Thus, FRP and DRP both have the property of temporal summation.

THE EFFECT OF REMOTE SEGMENTAL ELECTRO-ACUPUNCTURE ON THE FLEXION REFLEX POTENTIAL AND THE DORSAL ROOT POTENTIAL / 西安交通大学学报(医学版)

Deseription was given of the effect of electric acupuncture of Neiguan point on the flexion reflex potential (FRP) of the hindlimbs and the dorsal root potential (DRP). On the intact and awake rats, the graded train stimulation (three pulses, 5ms interval, 0.5ms duration) was given to the sural nerve (a pure cutancous n(?), the C-FRP and C-DRP with their proper amplitudes (70～80% maximum) were obtained on the hamstring nerve (a group of nerves innervating the hindlimb flexors) and L5 dorsal root respectively. Then the electric acupuncture with low freqency and low intensity (4Hz, 1～3V)and low freqency and high intensity ( 4Hz, 20～40V), lasting 5 minutes, was given to the ipsilateral Neiguan point. After acupuncture, the amplitudes of both C-FRP and C-DRP decreased without change of their latebcues. The former one declined heavier and recovered slower than the latter one did. The A-FRP and A-DRP were not affected. Te result of the experiment suggests that the ipsilatcral Neiguan point cletric acupuncture can induce hindlimb's analgesia, the presynaptic inhibition might be involved in the mechanism of such analgesia.