Abstract
Neuropathic pain is a severely disabling state that affects more than 15 millions of people in the world. This type of pain may be experienced after nerve injury. In the neuropathic pain state, touch stimulation frequently evokes strong pain sensation. We have previously shown that P2X4 receptors (P2X4Rs), which are upregulated in activated microglia in the spinal cord after nerve injury (Nature, 2003), and the stimulation of P2X4 causes release of brain-derived neurotrophic factor (BDNF) (Nature, 2005). BDNF causes a collapse of transmembrane anion gradient of lamina I neurons, and this results in changing the inhibitory action of GABA to excitatory one. Thus, we postulate that BDNF released by the stimulation of P2X4 in microglia is a crucial signalling molecule evoking the modal sift. We have also examined the mechanisms of the up-regulation of P2X4Rs in microglial cells. We found that fibronectin (FN), an extracellular matrix protein, increased P2X4R expression in microglia via an interaction with integrins (Glia, 2006) through activation of PI3K and MEK/ERK. Lyn tyrosine kinase is also required for this upregulation (Glia, 2008). These results indicate that FN may be regulators acting directly and indirectly on the P2X4R gene in microglia. Understanding of mechanisms underlying P2X4R expression in spinal microglia may lead to new strategies for the management of neuropathic pain. [J Physiol Sci. 2008;58 Suppl:S26]
