Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: A randomized, controlled pilot study

Brain Stimulation Laboratory, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President St., PO Box 250861, Charleston, SC 29425, USA.
Pain (Impact Factor: 5.21). 07/2011; 152(11):2477-84. DOI: 10.1016/j.pain.2011.05.033
Source: PubMed


Transcranial magnetic stimulation (TMS) of the prefrontal cortex can cause changes in acute pain perception. Several weeks of daily left prefrontal TMS has been shown to treat depression. We recruited 20 patients with fibromyalgia, defined by American College of Rheumatology criteria, and randomized them to receive 4000 pulses at 10 Hz TMS (n=10), or sham TMS (n=10) treatment for 10 sessions over 2 weeks along with their standard medications, which were fixed and stable for at least 4 weeks before starting sessions. Subjects recorded daily pain, mood, and activity. Blinded raters assessed pain, mood, functional status, and tender points weekly with the Brief Pain Inventory, Hamilton Depression Rating Scale, and Fibromyalgia Impact Questionnaire. No statistically significant differences between groups were observed. Patients who received active TMS had a mean 29% (statistically significant) reduction in pain symptoms in comparison to their baseline pain. Sham TMS participants had a 4% nonsignificant change in daily pain from their baseline pain. At 2 weeks after treatment, there was a significant improvement in depression symptoms in the active group compared to baseline. Pain reduction preceded antidepressant effects. TMS was well tolerated, with few side effects. Further studies that address study limitations are needed to determine whether daily prefrontal TMS may be an effective, durable, and clinically useful treatment for fibromyalgia symptoms.

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    • "However, it was shown in these patients that the analgesic effects of unilateral rTMS of M1 were not strictly somatotopic (Lefaucheur et al., 2006b). Consistent with these data, several studies, both in healthy volunteers (Moisset et al., 2015; Nahmias et al., 2009) and patients with fibromyalgia (Mhalla et al., 2011; Passard et al., 2007; Short et al., 2011) and myofascial pain syndrome (Dall'Agnol et al., 2014), have confirmed that unilateral rTMS of M1 or DLPFC induces bilateral diffuse analgesic effects, although the magnitude of the contralateral effects may be slightly higher (Passard et al., 2007). 3. Mechanisms of action of rTMS-induced analgesic effects The data briefly summarized above indicate that unilateral rTMS of M1 and DLPFC induces diffuse analgesic effects on both experimental and clinical pain. "
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    ABSTRACT: Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that allows cortical stimulation. Recent studies have shown that rTMS of the primary motor cortex or dorsolateral prefrontal cortex decreases pain in various pain conditions. The aim of this review was to summarize the main characteristics of rTMS-induced analgesic effects and to analyse the current data on its mechanisms of action. Databases: Medline, PubMed and Web of Science were searched for studies on the analgesic effects and mechanisms of rTMS-induced analgesic effects. Studies on epidural motor cortex stimulation (EMCS) were also included when required, as several mechanisms of action are probably shared between both techniques. Results: Stimulation site and stimulation parameters have a major impact on rTMS-related analgesic effects. Local cortical stimulation is able to elicit changes in the functioning of distant brain areas. These modifications outlast the duration of the rTMS session and probably involve LTP-like mechanisms via its influence on glutamatergic networks. Analgesic effects seem to be correlated to restoration of normal cortical excitability in chronic pain patients and depend on pain modulatory systems, in particular endogenous opioids. Dopamine, serotonin, norepinephrine and GABAergic circuitry may also be involved in its effects, as well as rostrocaudal projections. Conclusions: rTMS activates brain areas distant from the stimulation site. LTP-like mechanisms, dependence on endogenous opioids and increase in concentration of neurotransmitters (monoamines, GABA) have all been implicated in its analgesic effects, although more studies are needed to fill in the still existing gaps in the understanding of its mechanisms of action.
    European journal of pain (London, England) 10/2015; DOI:10.1002/ejp.811 · 2.93 Impact Factor
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    • "Short et al. [16] tested the effects of left prefrontal cortex rTMS on pain in fibromyalgia patients and observed a significant mean 29% reduction of pain ratings in the real TMS group as compared to a non-significant mean 4% reduction in the sham TMS group. We observed a 31% and 56% reduction of pain ratings for configuration B (10Hz) and configuration E, respectively, at the 4 weeks post treatment compared to 15% for both 4 coil 1 Hz and sham treatment. "
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    ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows for effects in surface cortical structures. The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients. Part 1: Different coil configurations were tested in a placebo-controlled crossover design in volunteers (N = 16). Tonic pain was induced using a capsaicin/thermal pain model and functional brain imaging was performed by means of H215O positron emission tomography -- computed tomography (PET/CT) scans. Differences in NRS pain ratings between TMS and sham treatment (NRSTMS-NRSplacebo) which were recorded each minute during the 10 minute PET scans. Part 2: 16 fibromyalgia patients were subjected to 20 multi-coil rTMS treatments over 4 weeks and effects on standard pain scales (Brief Pain Inventory, item 5, i.e. average pain NRS over the last 24 hours) were recorded. A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers. In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz. This degree of pain control was maintained for at least 4 weeks after the final session. Multi-coil rTMS may be a safe and effective treatment option for acute as well as for chronic pain, such as that accompanying fibromyalgia. Further studies are necessary to optimize configurations and settings as well as to elucidate the mechanisms that lead to the long-lasting pain control produced by these treatments.
    Molecular Pain 07/2013; 9(1):33. DOI:10.1186/1744-8069-9-33 · 3.65 Impact Factor
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    • "No improvements in the Likert pain scale. Short et al (2011) "
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    ABSTRACT: Chronic pain is a common issue worldwide and remains a big challenge to physicians, particularly when the underlying causes do not meet any specific disease for settlement. Such medically unexplained somatic symptoms of pain that lack an integrated diagnosis in medicine have a high psychiatric comorbidity such as depression, and will require a multidisciplinary treatment strategy for a better outcome. Thus, most patients deserted management in spite of being inadequately treated and even presented with high resistance to analgesic drugs. Noninvasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS), has been used to treat refractory neuropathic pain and the analgesic efficacy is promising. So far, some case series and randomized rTMS studies have reported on patients with certain medically unexplained symptoms (MUSs) of pain (e.g., psychogenic pain or somatic symptoms in major depression and fibromyalgia). However, there is still no review article that is specific to the efficacy of rTMS on chronic unexplained symptoms of pain. Therefore, in the present review, we ventured to clarify the terminology and summarized the analgesic effects of rTMS on chronic MUSs of pain.
    06/2013; 51(2):81-7. DOI:10.1016/j.aat.2013.06.003
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