Glia Produce the Pain Signal: BDNF

Abstract

Shifting of the equilibrium potential for anions ( E anion ) in neurons of the spinal cord, such that the normally inhibitory neurotransmitter GABA (γ-aminobutyric acid) becomes a stimulatory one, is one of the mechanisms responsible for neuropathic pain. Coull et al. now show that brain-derived neurotrophic factor (BDNF) released from microglia is responsible for triggering this shift. Injection of adenosine triphosphate (ATP)-stimulated microglia or BDNF into the spinal cord of rats produced an increase in pain perception to touch stimuli, tactile allodynia, and slice preparations exhibited a shift in the E anion to a more positive value and a depolarizing response to application of GABA in slice preparations. Injection of BDNF function-blocking antibodies or proteins reversed the decrease in paw-withdrawal threshold, and the E anion was restored to a more negative value in the spinal slices. Injection of these function-blocking entities with the ATP-stimulated microglia prevented the microglia from producing tactile allodynia. Injection of ATP-stimulated microglia that could not produce BDNF also did not produce allodynia, confirming that the microglia are the source of the BDNF. Torsney and MacDermott discuss the importance of these results. J. A. M. Coull, S. Beggs, D. Boudreau, D. Boivin, M. Tsuda, K. Inoue, C. Gravel, M. W. Salter, Y. De Koninck, BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438 , 1017-1021 (2005). [PubMed] C. Torsney, A. B. MacDermott, A painful factor. Nature 438 , 923-925 (2005). [PubMed]