Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06006130 |
| Other study ID # |
16482 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2023 |
| Est. completion date |
May 30, 2025 |
Study information
| Verified date |
October 2023 |
| Source |
McMaster University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
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.
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.
