Spinal mechanisms of neuropathic pain: Is there a P2X4-BDNF controversy?

More than a decade ago the novel concept that glial cells are major players in the modulation of pain mechanisms in the spinal cord has started a prolific series of work addressing the modalities of neuron-glia communication. Mike Salter with Kazuhide Inoue laboratories introduced ATP as pivotal mediator for such communication via activation of P(2)X(4) receptors expressed by microglia in the dorsal horn ipsilateral to a peripheral nerve injury. Activation of P(2)X(4) receptors result in release of the neurotrophin BDNF, which, through the activation of neuronal TrkB receptors, alters neuronal excitability and this effect is associated with behavioural ipsilateral allodynia. This viewpoint article compares the evidence supporting a biological relevance of the P(2)X(4) and BDNF system in neuropathic pain with recent data which question such importance. Having read this article, readers will be able to formulate their own opinion on such controversy.