Plasma levels of BDNF and NGF — two nerve cell growth factors proposed to underlie fibromyalgia (FM) — were not found to be elevated in patients compared with healthy individuals, a study shows.
These findings contradict prior research and raise questions about the theory that BDNF and NGF are involved in increased sensitivity to pain felt by FM patients, and that they cause alterations in sensory nerve cells outside the brain and spinal cord.
The study, “No evidence for altered plasma NGF and BDNF levels in fibromyalgia patients,” was published in the journal Scientific Reports.
Chronic pain disorders such as fibromyalgia are thought to arise from alterations in central sensitization — an overactivation of nerve cells involved in pain perception in the brain and/or spinal cord — and peripheral sensitization, which is a hypersensitivity to stimuli originating at nerve cells in sensory organs.
In the quest to find biomarkers for these changes in sensitization, scientists have focused on factors that support the growth and survival of nerve cells (neurotrophic factors), including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF).
BDNF is widely expressed in the central nervous system (CNS, involving the brain and spinal cord), gut, and other tissues, and plays an important role in the survival and growth of nerve cells, and modulation of neurotransmitters (molecules used by nerve cells to send signals to other cells).
NGF is primarily involved in promoting the growth, proliferation, and survival of certain target nerve cells, especially those that transmit pain, temperature, and touch sensations (sensory neurons).
Excessive activity of these markers has been proposed to drive sensitization, and reports show that BDNF and NGF are increased in the cerebrospinal fluid (CSF, or the fluid that bathes the brain and spinal cord) of fibromyalgia patients.
Also, research indicates that BDNF is elevated in peripheral tissues, and plays a role in altered sensitivity to pain in FM patients. Yet, data linking these two biomarkers to FM, and to the peripheral sensitization process in particular, is still incomplete.
To provide better evidence and replicate prior findings in a large sample of patients, a team of researchers conducted a cross-sectional study to compare the levels of BDNF and NGF in the plasma of fibromyalgia patients versus healthy controls.
The study included 97 patients and 35 pain-free healthy controls, and the results showed that neither BDNF nor NGF levels differed between the two groups. Different statistical methods were used and led to the same conclusions.
“Our study fails to replicate the finding that peripheral BDNF is altered in fibromyalgia, and instead our findings suggest that plasma levels of growth factor appear normative in fibromyalgia, ” the researchers wrote.
Therefore, the findings “do not suggest that peripheral growth factors levels are not a pathophysiological feature of fibromyalgia, or that they contribute to the development of peripheral pain sensitization,” they added.
As prior research has broadly implicated BDNF as a biomarker for FM, and proposes that NGF is involved as well, these “null findings will adjust how clear the current study consensus appears,” the team stated.