Brain-derived neurotrophic factor (BDNF) as a driving force behind central sensitization pain: a new therapeutic target?   January 1st, 2015

The awareness is growing that neurotrophic factors, like brain-derived neurotrophic factor (BDNF), have a cardinal role in initiating and/or sustaining the hyperexcitability of central neurons in chronic pain patients. For example, microglial-derived BDNF contributes significantly to neuropathic pain. Therefore, potential pharmacological or conservative (e.g. exercise) treatment of neurotrophic factors like BDNF provides important new treatment avenues. 

BDNF is a protein (figure) encoded by the BDNF gene, and is a member of the neurotrophin class of growth factors. BDNF can be produced by a variety of cells, including sensory neurons, motor neurons, immune cells, microglia and astrocytes. In general, BDNF serves as a key regulator of synaptic plasticity in the peripheral and CNS, where it has a strong protective action promoting of neuronal survival and neurogenesis. 
Figure: structure of the BDNF protein

BDNF holds the capacity to alter pain pathways at every level, from the peripheral nociceptors to spinal cord neurons and brain. More specifically, BDNF on its own is able to sensitize peripheral nociceptors and results in increased excitability of second order neurons (in the dorsal horn). In the brain, BDNF shifts the balance from descending nociceptive inhibition towards nociceptive facilitation. BDNF has also been shown to activate descending nociceptive facilitation in the nucleus raphe magnus. BDNF is also an important facilitator of long-term potentiation (LTP) especially in regions involved in learning and memory like the hippocampus, which might be related to the generation of pain memories in chronic pain patients

How do we translate these (basic science) findings to clinical practice? First, it has to be mentioned that further human studies are required to back up the body of animal work regarding the role of BDNF in (mainly) neuropathic pain. Translational studies have been performed, but more such work is needed. Potential therapeutic options include indirect influencing of BDNF levels using exercise therapy, anti-inflammatory drugs, melatonin and repetitive transcranial magnetic stimulation. More specific targeting of BDNF’s receptors and signaling pathways is also possible, for instance by blocking the PAR2 – NK-kß signaling pathway, administration of phencyclidine for antagonising N-methyl-D-aspartate receptors or blockade of the adenosine A2A receptor. 

Reference and further reading: 

“Brain-derived neurotrophic factor (BDNF) as a driving force behind neuroplasticity in neuropathic and central sensitization pain: a new therapeutic target?” 
Nijs J, Meeus M, Versijpt J, Moens M, Bos I, Knaepen K, Meeusen R. 
Expert Opinion on Therapeutic Targets 2015; 19(4):565-76.
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