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A reduced functionality of Gi proteins as a possible cause of fibromyalgia
N Galeotti1, C Ghelardini, M Zoppi
1Department of Pharmacology, Headache Center, University of Florence, Italy.
Objective:
The etiopathogenesis of fibromyalgia (FM), a syndrome characterized by widespread pain and hyperalgesia, is still unknown. Since the involvement of Gi proteins in the modulation of pain perception has been widely established, the aim of the present study was to determine whether an altered functionality of the Gi proteins occurred in patients with FM.
Methods:
Patients with FM and other painful diseases such as neuropathic pain, rheumatoid arthritis (RA), and osteoarthritis, used as reference painful pathologies, were included in the study. The functionality, evaluated as capability to inhibit forskolin-stimulated adenylyl cyclase activity, and the level of expression of Gi proteins were investigated in peripheral blood lymphocytes.
Results:
Patients with FM showed a hypofunctionality of the Gi protein system. In contrast, unaltered Gi protein functionality was observed in patients with neuropathic pain, RA, and osteoarthritis. Patients with FM also showed basal cAMP levels higher than controls. The reduced activity of Gi proteins seems to be unrelated to a reduction of protein levels since only a slight reduction (about 20-30%) of the Gi3alpha subunit was observed.
Conclusions:
Gi protein hypofunctionality is the first biochemical alteration observed in FM that could be involved in the pathogenesis of this syndrome. In the complete absence of laboratory diagnostic tests, the determination of an increase in cAMP basal levels in lymphocytes, together with the assessment of a Gi protein hypofunctionality after adenylyl cyclase stimulation, may lead to the biochemical identification of patients with FM.
Insights
Fibromyalgia (FM) patients exhibit impaired Gi protein function, leading to increased cAMP levels. This Gi protein hypofunctionality is a novel biochemical marker potentially aiding in FM diagnosis.
Area of Science:
- Neuroscience
- Biochemistry
- Pain Research
Background:
- Fibromyalgia (FM) is a complex syndrome of widespread pain with unknown origins.
- Gi proteins play a crucial role in modulating pain perception.
Purpose of the Study:
- To investigate the functionality of Gi proteins in patients diagnosed with fibromyalgia.
- To determine if altered Gi protein function contributes to the pathogenesis of FM.
Main Methods:
- Assessed Gi protein functionality by measuring inhibition of forskolin-stimulated adenylyl cyclase activity.
- Investigated Gi protein expression levels in peripheral blood lymphocytes.
- Included patients with FM, neuropathic pain, rheumatoid arthritis, and osteoarthritis for comparison.
Main Results:
- Fibromyalgia patients displayed significantly reduced Gi protein functionality (hypofunctionality).
- Gi protein function remained normal in patients with neuropathic pain, rheumatoid arthritis, and osteoarthritis.
- Fibromyalgia patients had elevated basal cyclic adenosine monophosphate (cAMP) levels in lymphocytes.
- Reduced Gi protein activity was not attributed to a significant decrease in protein levels, with only a minor reduction in the Gi3alpha subunit.
Conclusions:
- Gi protein hypofunctionality represents the first identified biochemical alteration implicated in fibromyalgia pathogenesis.
- Measuring increased basal cAMP levels and assessing Gi protein hypofunctionality in lymphocytes could offer a biochemical method for identifying FM patients.
- This finding opens avenues for developing objective diagnostic tools for fibromyalgia.