|Ahead of print publication
Effect of repetitive transcranial magnetic stimulation in male patients of fibromyalgia
Vikas Kumar Tiwari1, Srishti Nanda1, Suvercha Arya1, Uma Kumar2, Renu Bhatia1
1 Department of Physiology, Pain Research and TMS Laboratory, All India Institute of Medical Sciences, New Delhi, India
2 Department of Rheumatology, All India Institute of Medical Sciences, New Delhi, India
Department of Physiology, Pain Research and TMS Laboratory, 6007, 6th Floor, Convergence Block, Ansari Nagar, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Male patients with fibromyalgia are a rarely studied population, yet they remain refractory to conventional medication. Here, we report the effect of repetitive transcranial magnetic stimulation (rTMS) on pain status in four male patients (aged 40.3 ± 8.49 years, right-handed) with fibromyalgia. It was found that the pain intensity reported at baseline was 6.50 ± 1.29 on the 11-point numerical pain rating scale that changed to 2.00 ± 1.15 posttherapy. Minor headache was noted in the 1st week of the therapy. rTMS could be beneficial for pain relief in male patients with fibromyalgia. Future investigations may focus on investigating more treatment options, such as rTMS, for male patients with fibromyalgia.
Keywords: Chronic pain, fibromyalgia, males, prefrontal cortex, transcranial magnetic stimulation
| Introduction|| |
Fibromyalgia is a chronic pain disorder, characterized by fatigue, tenderness, sleep disturbances, and compromised cognitive abilities. Recent survey suggests that up to 1% of the male population worldwide could be affected by fibromyalgia syndrome (FMS) that is different from our long-held understanding of the disease. It is, therefore, not surprising that the search for treatment options has been severely limited for male patients with fibromyalgia.,, Since our previous study has shown it to be an effective therapy in female patients with fibromyalgia, we explored the role of repetitive transcranial magnetic stimulation (rTMS) intervention on pain status and related outcomes in male patients. Thus, for the present study, it was hypothesized that rTMS, a promising noninvasive treatment for fibromyalgia, is likely to play a beneficial role in male patients.
| Case Report|| |
A 26-year-old married male with no children had a history of fibromyalgia for 2 years; according to the patient, the symptoms initially manifested about 8 years back. The patient was a postdoctoral researcher in medical field in a tertiary care hospital and research center as a full-time employee and had a sedentary lifestyle. He felt pain in the lower back and calf and had mild headache intermittently through the course of the day; each bout of pain was felt as dull, boring, and aching, which often caused him to feel tired. He also complained of whole-body fatigue and nonrestorative, unrefreshing sleep. The symptoms were aggravated by prolonged sitting, emotional distress, and cold weather. Some degree of relief was felt after using analgesic drugs, local pressure or bandage, and sprays. The magnetic resonance imaging revealed desiccation and disc protrusion at L4–L5 region. Although there was a history of fall from height, there was no concurrent evidence from the magnetic resonance imaging. After diagnosis, a standard prescription for fibromyalgia was advised (325 mg of acetaminophen, 37.5 mg tramadol, 125 mg of calcium tablets, 100 mg of gabapentin, and 75 mg of pregabalin) [Supplementary Table S1]. After 8 months of aforementioned medications, the symptoms remained unresolved.
A 35-year-old married male with two children, who was a shopkeeper by profession with a sedentary lifestyle, literate, and staying in a rural area; had a symptom of insidious onset in the lower back region for 10 years. He reported that he felt fatigue, headache, and sleep disturbances. In the past few years, the pain symptoms increased in intensity, especially in the elbows and temporal regions. The patient believed that his primary problem was lower back pain. He described his pain as stabbing, cramping, tingling, dull, nagging, and heaviness in the limbs. Tender points were reported by the patient in various parts of the body [Figure 1]. The pain aggravated with mental tension, insomnia, and physical activity. Rest, limited body movements, and analgesic sprays were used to alleviate the pain along with yoga-based intervention for pain relief. Other investigations such as bone scan (dual-energy X-ray absorptiometry) and X-ray of joints were normal. Additional investigations included HLA-B27 to rule out seronegative spondyloarthritis. He was diagnosed with FMS, approximately 4 years back. After 12 months of unsatisfactory treatment [Supplementary Table S1] with the standard prescription for FMS, he reported to our laboratory.
A 29-year-old male had 7.5 years of chronic pain in both lower limbs that gradually spread over the whole body. The patient had a sedentary job in a private firm. He complained of drilling, hurting, vicious, penetrating, agonizing type of pain in the bilateral mandibular joint area, especially behind the ears, and pain on the sides of the neck (bilateral clavicular and scapular area). Recently, he started having pain in the temporal region. At present, the maximum intensity of pain was present in the lower back region. He also complained about lack of libido, which was attributed to pain around the testicular region. At times, the pain was severe enough to interrupt sleep. The pain symptoms aggravated in severity with maximum discomfort in the thighs and lower back region. Rest, limitations of body movements, and sprays were used to deal with the pain. The patients felt mild but transient improvement after 3 years of standard prescription of medications [Supplementary Table S1]. He had tried adjunct treatments such as massage, exercise, and yoga; avoiding prolonged standing.
A 35-year-old male, a truck driver by profession, came with a history of chronic pain for 12 years due to arthritis in the bilateral limbs, which gradually involved the whole body. He had a family history of arthritis. At present, the pain had gradually increased for the last 2 years, to the point, that it interfered in his day-to-day activity. It started from pain in the knee joint to the sternal area, elbow, lower back pain, and fingers. Most painful sites were lower limbs, flanks, knee joints, lateral aspect of sole of the leg, and nape of the neck. He further described the pain as dull throbbing, annoying, crushing, and radiating type with limited joint movements and tenderness. After some time, the severity of pain led to difficulty in walking and climbing upstairs and downstairs. The patient reported anxiety due to financial challenges, increased sleep latency, interrupted sleep, and nightmares. Previous medical history included cured pulmonary tuberculosis. On investigations, seronegative arthropathy was found and he was treated earlier for polyarthralgia before being diagnosed with fibromyalgia. Regular medications for 2 years did not improve symptoms [Supplementary Table S1].
| Methodology|| |
Low-frequency (1 Hz) rTMS intervention (Neuro-MS/D magnetic stimulator, Neurosoft, Russia) was given by placing the coil at 45° to the sagittal plane at a predetermined therapy site (dorsolateral prefrontal cortex). Total of 1200 pulses at 90% of motor threshold were administered for 26 min. Motor hotspot and dosage estimation was performed just a day before the first day of therapy and marked with a pen. The estimated doses of rTMS of the patients were calculated as per their resting motor threshold., Motor thresholds were updated every five sessions. Twenty sessions were given across 4 weeks (five consecutive working days in a week). The participants were screened for any contraindications to TMS, such as metallic implants, intracardiac lines, increased intracranial pressure, and recent head trauma. Other factors include any conditions that increased risk of seizure or taking drugs that lowers the seizure threshold. Demographic features included age, BMI, socioeconomic status, and stimulation intensity have been mentioned in [Table 1]. rTMS therapy was provided free of cost and after written informed consent. The primary outcome of the study was improvement in pain intensity; the secondary outcomes were pain descriptors, cognitive assessment, daytime somnolence, and sleep quality. Outcome measures were assessed before and after the therapy (24 h from the session).
Pain intensity was measured by 11-pt numerical pain rating scale. Tender points have been counted and measured according to the guidelines. Standard questionnaires and their domains have been used to assess pain perception (mcgillpain questionnaire), cognitive assessment (mini mental state examination),, sleep quality (pittsburgh sleep quality index), and daytime somnolence (epsworth sleepiness scale).
| Results|| |
The recruited patients had pain intensity with an average of 6.22 ± 1.38 and experienced an average relief of 2.00 ± 1.15 units [Table 1]. Patient 1 who reported dull, boring, and aching course was alleviated posttherapy; frequency of recurrence of pain and emotional distress also decreased. Patient 2 found that the pain symptoms in the elbows and temporal regions decreased satisfactorily, though his primary problem of lower back pain remained. Patient 3 described pain in the bilateral mandibular joints, behind the ears and on the sides of the neck area, all of which improved except in the clavicular and scapular area. Patient 4 described this pain as dull, throbbing, crushing nature, and it was reduced posttherapy, although limited joint movements remained. Patient 2 and Patient 4 reported no change in evaluative component and Patient 3 and Patient 4 reported no change in miscellaneous component of MPQ. Other parameters improved in all remaining patients.
As seen in the [Table 2], one patient had cognitive impairment (assessed by MMSE) at baseline, which improved to the normal range after therapy. Three out of four male patients had poor sleep, but Patient 2 had a global score (assessed by PSQI) within normal limit. Apart from that, Patient 4 mentioned severe problem in sleep latency for about 30–60 min for more than three times in a week. All patients felt that subjective sleep quality and daytime sleepiness scores improved posttherapy. Sleep duration and habitual sleep deficiency remained unchanged post therapy. Sleep latency scores improved in three patients except in Patient 1. Sleep disturbances were present in all four and improved in two patients, though there was no improvement in the remaining two patients. Daytime dysfunction improved in Patient 1 and Patient 2 and remained same as baseline in the other two patients. It is important to note that none of patients were on sleep medications before, during, or after therapy. At baseline, daytime somnolence, as assessed by ESS, was found to be impaired in two out of four patients (Patient 3 and Patient 4). These values remained unchanged after therapy.
|Table 2: Effect of repetitive transcranial magnetic stimulation therapy on outcome measures: Pain intensity was assessed with numerical|
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All participants completed twenty sessions of therapy. Patient 1 reported mild discomfort when recording resting motor threshold; Patient 2 reported minor headaches and heaviness in the head after first two sessions of therapy. Patient 3 postponed three sessions of therapy during the 1st week of treatment due to severe body pain. No patient left the therapy before completion due to discomfort, side effects, or adverse effects.
| Discussion|| |
In the present case-based review, we have presented the effect of rTMS therapy on pain status in male patients with fibromyalgia.
The previous studies stated that FMS primarily affects females (female: male ratio was 9:1); however, recent reports have contradicted the notion. Furthermore, the clinical symptoms experienced by male patients may be slightly different from that of females. They have lesser number of tender points, different pain descriptors, attention deficits, and poorer sleep quality., However, with a recent change in the way fibromyalgia is defined and diagnosed, the focus has moved away from the number of tender points to a whole plethora of symptoms including deficits in cognitive function, sleep, and overall fatigue. The latest survey estimates the prevalence to be about 1% for males and 3.98% for females, reducing, the gap between the two sexes considerably. It has been postulated that it is these differences in disease representations that make the diagnosis difficult, resulting in poorer prognosis. Till now, few case reports,, have explored possible treatment strategies for male patients with FMS [Table 3].
|Table 3: Summary of interventional reports in male patients with fibromyalgia syndrome|
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rTMS has recently emerged as a potential therapy for the management of several chronic pain syndromes, including fibromyalgia. Our laboratory has recently shown that low-frequency rTMS (1 Hz) of the right DLPFC is effective for patients with fibromyalgia, but the patient cohort included only females. A recent rTMS study mentioned recruiting two male (out of total 26) patients with fibromyalgia, but they did not comment on male-specific characteristics or outcome.
With this perspective, the purpose of the present study was to determine the effect of 4-week long rTMS therapy on pain status, cognitive function, and sleep quality in male patients with FMS. Although all four patients experienced pain relief, only Patient 1 and Patient 2 experienced clinically significant pain relief. The tender points were also reduced [Figure 1]. The most prominent improvement was seen in the sensory and affective-motivational domain of pain perceptions, using MPQ. Both PSQI and ESS scores showed that rTMS was beneficial. Patients reported maximum improvement in subjective sleep quality and sleep latency, whereas mild improvement was seen in sleep duration and daytime sleepiness. In only one out of four patients who had impairment at baseline, the scores changed from “impaired” to “normal range” after rTMS therapy. The therapy was found to be safe for all participants.
Despite promising results, there are some limitations of the present study. First, the results involving four patients can certainly not be extrapolated to a larger population. Second, the localization of dorsolateral prefrontal cortex was done using scalp landmarks that may have an interindividual variability. Third, it remains to be figured out whether the effect of rTMS is sex specific. Despite these limitations, this is the first report of effect of rTMS therapy in male patients with FMS, to the best of our knowledge.
| Conclusion|| |
The study shows that rTMS has a beneficial effect on pain status, cognition, and daytime somnolence in male patients with FMS. Other studies have also found beneficial effect of strength training and ta'i-chi on pain and other related symptoms. Together, both lines of evidence may serve as an impetus for investigating the underlying pathophysiology of FMS, in male patients, an otherwise neglected field of research, and conduct more interventional studies in the same direction.
Declaration of patient consent
The authors certify that written informed consent was taken prior to recruitment. In the form, the patients gave their consent to participate in this case-based review. Further, it has been stated that due efforts was made to keep their confidentiality and privacy were maintained through course of study.
The authors acknowledge the contributions of Dr. Ragini Adhikari for preparing the figure and drafting and critically revising the manuscript and Dr. Danveer Bhadu and Dr. Sandeep for patient recruitment.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]