Neurophysiology of Fibromyalgia

Fibromyalgia Clinical Trial

Official title: Investigating the Neurobiological Contributions to Pain in Patients With Fibromyalgia

Status Not yet recruiting

Clinical Trial Summary

Fibromyalgia is a syndrome associated with fatigue and chronic pain, leading to significant physical limitations and impaired quality of life. There are several challenges that complicate the diagnosis and management of fibromyalgia. The etiology is not well defined, as there are several proposed factors that may trigger the genesis of pain in fibromyalgia including physical and/or emotional life stressors, and genetic predispositions involving neuromodulator pathways. Chronic pain in fibromyalgia arises in the absence of tissue pathology, and consequently a lack of consensus on reliable diagnostic criteria. Understanding the neurophysiology of fibromyalgia would aid in the discovery of objective biomarkers for diagnosis. Therefore, the goals of this study are to: 1. Compare the neurophysiological responses in fibromyalgia compared to healthy controls. 2. Determine whether a two-week rTMS protocol will alter pain in individuals with fibromyalgia.

Clinical Trial Description

Fibromyalgia is a syndrome associated with fatigue and chronic pain, leading to significant physical limitations and impaired quality of life. Fibromyalgia affects 1.7% of Canadians, with a higher prevalence in females compared to males at 9:1 [1]. There are several challenges that complicate the diagnosis and management of fibromyalgia. The etiology is not well defined, as there are several proposed factors that may trigger the genesis of pain in fibromyalgia. Chronic pain in fibromyalgia arises in the absence of tissue pathology, and consequently a lack of consensus on reliable diagnostic criteria. Understanding the pathophysiology of fibromyalgia would aid in the identification of objective biomarkers that could be used for diagnosis. Multiple theories have been posited to explain the genesis of chronic pain. The gate control theory describes the attenuation of pain signals in the spinal cord prior to cortical processing, and it has been hypothesized that loss of this gate control leads to the genesis of chronic pain [2]. Gate control can be observed by reduction of afferent signals during active muscle contraction. For example, the amplitude of the somatosensory-evoked potential (SEP) is attenuated during active contraction [3]. To our knowledge, it is unknown whether such gate control is observed in fibromyalgia. The lack of gate control may contribute to chronic pain in this population. The sensorimotor theory suggests that incongruency between motor intention and sensory feedback underlies chronic pain where there is an absence of tissue pathology [4]. This may align with the genesis of fibromyalgia, given the findings that those with fibromyalgia have altered tactile and proprioceptive functioning [5]. Corticomuscular coherence (CMC) is a useful tool that uses electroencephalography (EEG) and electromyography (EMG) to probe the synchrony of neural firing between the brain and muscle [6]. To our knowledge, it is unknown how the magnitude of CMC varies in fibromyalgia compared to healthy controls. Non-invasive brain stimulation in the form of Transcranial Magnetic Stimulation (TMS) has been used to probe the activity of corticospinal and cortical networks in fibromyalgia. When TMS pulses are delivered in a repetitive train, a protocol known as repetitive TMS (rTMS), short-term neuroplasticity can be induced (i.e., a change in the activity of neurons in the brain). In fibromyalgia, Mhalla et al. [7] found that 5 days of 10 Hz rTMS reduced pain intensity and improved quality of life metrics. It is unknown whether a longer intervention period could lead to greater analgesic effects. Finally, central sensitization may explain the widespread chronic pain experienced in fibromyalgia. There are several neuromodulators that contribute to the neurobiology of central sensitization and may be implicated in this condition including serotonin, dopamine, and brain-derived neurotrophic factor (BDNF). Serotonin is linked to pain modulation, such that increased levels of 5-HT are associated with hyperalgesia [8]. BDNF has been implicated in the genesis of neuropathic pain [9]. In fibromyalgia compared to healthy controls, serum BDNF levels have been reported to be higher [10]. Abnormal dopamine function may also be associated with fibromyalgia [11]. Positron-emission tomography (PET) studies show lower cortical dopamine D2/D3 binding availability in fibromyalgia compared to healthy controls [12]. Ultimately, a combination of events may lead to widespread chronic pain in fibromyalgia. Understanding the neurophysiology of fibromyalgia would aid in the discovery of objective biomarkers for diagnosis. Therefore, the goals of this study are to: 1. Compare the neurophysiological responses in fibromyalgia compared to healthy controls. 2. Determine whether a two-week rTMS protocol will alter pain in individuals with fibromyalgia. 1. M. B. Yunus, "The role of gender in fibromyalgia syndrome," Curr Rheumatol Rep, vol. 3, no. 2, pp. 128-134, 2001, doi: 10.1007/S11926-001-0008-3. 2. R. Melzack, "Evolution of the neuromatrix theory of pain. The Prithvi Raj Lecture: presented at the third World Congress of World Institute of Pain, Barcelona 2004," Pain Pract, vol. 5, no. 2, pp. 85-94, Jun. 2005, doi: 10.1111/J.1533-2500.2005.05203.X. 3. H. Nakata, K. Inui, T. Wasaka, Y. Nishihira, and R. Kakigi, "Mechanisms of differences in gating effects on short-and long-latency somatosensory evoked potentials relating to movement," Brain Topogr, vol. 15, no. 4, pp. 211-222, Jun. 2003, doi: 10.1023/A:1023908707851. 4. A. D. Vittersø, M. Halicka, G. Buckingham, M. J. Proulx, and J. H. Bultitude, "The sensorimotor theory of pathological pain revisited," Neurosci Biobehav Rev, vol. 139, Aug. 2022, doi: 10.1016/J.NEUBIOREV.2022.104735. 5. S. Toprak Celenay, O. Mete, O. Coban, D. Oskay, and S. Erten, "Trunk position sense, postural stability, and spine posture in fibromyalgia," Rheumatol Int, vol. 39, no. 12, pp. 2087-2094, Dec. 2019, doi: 10.1007/S00296-019-04399-1/TABLES/2. 6. A. Chowdhury, H. Raza, Y. K. Meena, A. Dutta, and G. Prasad, "An EEG-EMG correlation-based brain-computer interface for hand orthosis supported neuro-rehabilitation," J Neurosci Methods, vol. 312, pp. 1-11, Jan. 2019, doi: 10.1016/J.JNEUMETH.2018.11.010. 7. A. Mhalla et al., "Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia," Pain, vol. 152, no. 7, pp. 1478-1485, 2011, doi: 10.1016/J.PAIN.2011.01.034. 8. E. A. Ovrom, K. A. ; Mostert, S. ; Khakhkhar, D. P. ; Mckee, P. ; Yang, and Y. F. A. Her, "A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia," Biomedicines 2023, Vol. 11, Page 1119, vol. 11, no. 4, p. 1119, Apr. 2023, doi: 10.3390/BIOMEDICINES11041119. 9. K. Obata and K. Noguchi, "BDNF in sensory neurons and chronic pain," Neurosci Res, vol. 55, no. 1, pp. 1-10, May 2006, doi: 10.1016/J.NEURES.2006.01.005. 10. A. Deitos et al., "Clinical Value of Serum Neuroplasticity Mediators in Identifying the Central Sensitivity Syndrome in Patients With Chronic Pain With and Without Structural Pathology," Clin J Pain, vol. 31, no. 11, pp. 959-967, 2015, doi: 10.1097/AJP.0000000000000194. 11. P. B. Wood, M. F. Glabus, R. Simpson, and J. C. Patterson, "Changes in gray matter density in fibromyalgia: correlation with dopamine metabolism," J Pain, vol. 10, no. 6, pp. 609-618, Jun. 2009, doi: 10.1016/J.JPAIN.2008.12.008. 12. D. S. Albrecht et al., "Differential dopamine function in fibromyalgia," Brain Imaging Behav, vol. 10, no. 3, pp. 829-839, Sep. 2016, doi: 10.1007/S11682-015-9459-4/FIGURES/4. ;

Related Conditions & MeSH terms

• Fibromyalgia
• Myofascial Pain Syndromes

• NCT number: NCT06006130
• Study type: Interventional
• Source: McMaster University
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 1, 2023
• Completion date: May 30, 2025