Associations among serum VEGF and CGRP levels with the peripheral vascular blood flow of the skin of the hands in women with FM 2023 Casas-Barragán

Andy · Feb 18, 2023

Abstract

Background
Fibromyalgia (FM) is a long-term condition of unknown physiopathology, whose hallmark symptoms are diffuse musculoskeletal chronic pain and fatigue.

Objectives
We aimed to analyze the associations among serum vascular endothelial growth factor (VEGF) and calcitonin gene-related peptide (CGRP) levels with the peripheral temperature of the skin of both hands and the core body temperature in patients with FM and healthy controls.

Methods
We conducted a case-control observational study with fifty-three women diagnosed with FM and twenty-four healthy women. VEGF and CGRP levels were spectrophotometrically analyzed in serum by enzyme-linked immunosorbent assay. We used an infrared thermography camera to assess the peripheral temperature of the skin of the dorsal thumb, index, middle, ring, and pinkie fingertips and dorsal centre as well as the palm thumb, index, middle, ring, and pinkie fingertips, palm centre and thenar and hypothenar eminences of both hands and an infrared thermographic scanner to record the tympanic membrane and axillary temperature.

Results
Linear regression analysis adjusting for age, menopause status, and body mass index showed that serum VEGF levels were positively associated with the maximum (β = 65.942, 95% CI [4.100,127.784], p = 0.037), minimum (β = 59.216, 95% CI [1.455,116.976], p = 0.045), and mean (β = 66.923, 95% CI [3.142,130.705], p = 0.040) temperature of the thenar eminence of the non-dominant hand, as well as with the maximum temperature of the hypothenar eminence of the non-dominant hand (β = 63.607, 95% CI [3.468,123.747], p = 0.039) in women diagnosed with FM.

Conclusions
Mild associations were observed between serum VEGF levels and the peripheral temperature of the skin in hand areas in patients with FM; therefore, it is not possible to establish a clear relationship between this vasoactive molecule and vasodilation of the hands in these patients.

Open access, https://www.sciencedirect.com/science/article/abs/pii/S0306456523000104

Hutan · Feb 20, 2023

Granada, Spain

So VEGF, which we know is related to blood vessel growth, vasodilation and vascular permeability (more background on the VEGF thread):

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, exerts important roles in the circulatory system, since it stimulates blood vessels growth, endothelial cell survival, and angiogenesis, and regulates the blood microcirculation through the activation of its receptors, VEGFR-1 and VEGFR-2
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It mentions some more studies of VEGF in fibromyalgia, with contradictory results (doesn't mention the recent 2022 one which found no difference in VEGF levels)

There are very few studies available that have examined VEGF in FM patients, showing contradictory results (Blanco et al., 2010; Karadağ et al., 2019; Kim et al., 2010).
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Calcitonin gene-related peptide (CGRP) - vasodilation and temperature control. Suggestions that it might be causing pain in fibromyalgia. References a 2020 study that found higher levels of CGRP in fibromyalgia. Very interesting that that 2022 study also found higher levels of CGRP in fibromyalgia.

Calcitonin gene-related peptide (CGRP) is a neuropeptide widely distributed in the brain, gut and perivascular nerves that has important biological effects on gastrointestinal, endocrine, and central nervous system (Russell et al., 2014). CGRP exerts both neurotransmitter and vascular functions. It is a potent endogenous vasodilator associated to increased skin temperature, vasodilation, and sweating functions (Brain and Grant, 2004; Oliveira et al., 2018). CGRP is also a neurotransmitter involved in central and peripheral sensitization, which is the main hypothesis on the physiopathology of FM, exerting pro-nociceptive effects (Iyengar et al., 2017; Russell et al., 2014). To our knowledge, only one study has evaluated CGRP levels in patients with FM, finding higher levels in patients in comparison to controls (Korucu et al., 2020).
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Interesting discussion of how problems in microvascular circulation might be happening in fibromyalgia, as a result of altered neural vasoregulation. Mentions arteriovenous anastomoses (AVAs) connections between the small arterioles and venues in the hands which help with heat regulation.

Previous studies have shown microvascular circulation impairments and reduced blood flow and oxygenation to the musculoskeletal deep tissue caused by changes in the sensory innervation to the arteriovenous anastomoses (AVAs) in the skin of patients with FM (Albrecht et al., 2013; Morf et al., 2005). AVAs are direct connections between small arterioles and venules located in the depth of glabrous skin of the dorsal and palm of the hands, whose main role is to transport the heat from the human body's core to peripheral skin regions (Walløe, 2016). To this regard, Albrecht et al. (2013) found an altered neural vasoregulation at the hands AVAs in a population of women diagnosed with FM, which was characterized by an excessive peptidergic sensory innervation. This sensory overrepresentation stimulates dermal peptidergic sensory fibers, activating the local “axon-reflex” and releasing vasoactive neuropeptides and inflammatory markers at the blood flow, which can modify the mechanisms that operate among capillaries and peripheral arterioles, thus altering both the peripheral blood microcirculation and thermogenesis process in patients with FM (Albrecht et al., 2013; Walløe, 2016).
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Hutan · Feb 20, 2023

On the other hand, thermography is a novel tool to assess vascular reactivity since provides an optimal relationship between peripheral blood flow changes and the thermal properties of the skin
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A little pun in a paper on blood circulation in hands.

Hutan · Feb 20, 2023

Unfortunately I can only see 'section snippets' after that. It sounds as though the 53 women with fibromyalgia had slightly warmer hands than the controls. What I really want to know about are the levels of VEGF and CGRP.

If anyone can see the whole paper, maybe you could let us know?

Hutan · Feb 20, 2023

We have a thread about migraine treatments, in 2017 there was a new one that is a CGRP receptor inhibitor, erenumab.
Migraine treatments

It would be really interesting to know if anyone with fibromyalgia or ME/CFS has tried that migraine treatment.

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Associations among serum VEGF and CGRP levels with the peripheral vascular blood flow of the skin of the hands in women with FM 2023 Casas-Barragán

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Associations among serum VEGF and CGRP levels with the peripheral vascular blood flow of the skin of the hands in women with FM 2023 Casas-Barragán

Andy Committee Member

Hutan Moderator Staff Member

Hutan Moderator Staff Member

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Hutan Moderator Staff Member

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