ATP receptors in the pain signaling: Glial contribution in neuropathic pain

There is abundant evidence that extracellular ATP has an important role in pain signaling at both the periphery and in the CNS. The focus of attention now is on the possibility that ATP and its receptor system might play important roles in chronic pathological pain states, particularly in neuropathic pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, diabetes, or infection. This type of pain can be so severe that even light touching can be intensely painful. Unfortunately, this state is generally resistant to currently available treatments. In this review, we summarize the role of ATP receptor P2X4 and P2X7 in spinal microglia in neuropathic pain. The activated microglia express P2X4 after nerve injury, which can be stimulated by endogenous ATP, resulting in the release of brain-derived neurotrophic factor that is one of key molecules involving in neuropathic pain. The stimulation of microglial P2X7 releases cytokines including TNF-α and IL- 1β. Understanding the key roles of these ATP receptors may lead to new strategies for the management of intractable chronic pain.