BDNF is Doubly Bad

BDNF is brain derived neurotrophic factor.

BDNF turns out to both enhance excitatory neurons transmitting pain and to inhibit the “tonic” neurons which would suppress pain. How bad can a molecule get?

In a bit of surprise in the literature, Lu et al in J Physiol. 2007 Aug 30; have found BDNF not only enhances excitation, it blocks inhibition of pain. The authors set up a model of PERIPHERAL nerve injury pain, that of chronic constriction of the sciatic nerve, and found that “delay” or excitatory neurons were enhanced presynaptically, whereas “tonic” or inhibitory neurons were suppressed presynaptically and postsynaptically.

The excitatory neurons are reflected in miniature excitatory presynaptic current, without directly affecting AMPA receptors postsynaptically. (The synapae is of course the connection point between any two neurons). The action of BDNF resulted in increased intracellular calcium (Ca2+).

As we have pointed out, increases in intracellular Calcium cause generalized hyperactivity.

This study is the first to demonstrate both a pain excitatory role and an inhibition blocking role for BDNF. Both results appear to result from the presence of increased Ca2+, which increases membrane excitability. Although these authors were studying central sensitization, which is the transfer of peripheral nerve injury to central nervous sytem hyperactivity (a somewhat different thing from central pain), many of the same mechanisms may be at play in pain from primary injuries of the central nervous system, or central pain.