BACKGROUND P2X4 receptor (P2X4R), a purinoceptor expressed in activated spinal microglia, plays a key role in the pathogenesis of neuropathic pain. Spinal nerve injury induces up-regulation of P2X4R on activated microglia in the spinal cord, and blockade of this receptor can reduce neuropathic pain. The present study was undertaken to determine whether paroxetine, an inhibitor of P2X4R, could a...

Protein allosteric modulation is a pillar of metabolic regulatory mechanisms; this concept has been extended to include ion channel regulation. P2XRs are ligand-gated channels activated by extracellular ATP, sensitive to trace metals and other chemicals. By combining in silico calculations with electrophysiological recordings, we investigated the molecular basis of P2X4R modulation by Zn(II) an...

P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P...

Accumulating evidence indicates that purinergic P2X4 receptors (P2X4R: cation channels activated by extracellular ATP) expressed in spinal microglia are crucial for pathological chronic pain caused by nerve damage, suggesting a potential target for drug discovery. We identified NP-1815-PX (5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1, 2-b][1,4]diazepine-2,4(3H,5H)-dione) as a no...

Evidence is accumulating to support the presence of P2X purinergic receptors in the heart. However, the biological role of this receptor remains to be defined. The objectives here were to determine the role of cardiac P2X receptors in modulating the progression of post-myocardial infarction ischemic heart failure and to investigate the underlying mechanism. The P2X4 receptor (P2X4R) is an impor...

Neuropathic pain, a debilitating pain condition, is a common consequence of damage to the nervous system. Neuropathic pain is often resistant to currently available analgesics. A growing body of evidence indicates that spinal microglia react and undergo a series of changes that directly influence the establishment of neuropathic pain states. After nerve injury, P2X4 receptors (P2X4Rs) are upreg...

Prostaglandin E2 (PGE2) is a key mediator of inflammation and contributes to pain hypersensitivity by promoting sensory neurons hyperexcitability. PGE2 synthesis results from activation of a multi-step enzymatic cascade that includes cyclooxygenases (COXs), the main targets of non-steroidal anti-inflammatory drugs (NSAIDs). Although NSAIDs are widely prescribed to reduce inflammatory symptoms s...

Neuropathic pain is still an extremely important problem in today's medicine because opioids, which are commonly used to reduce pain, have limited efficacy in this type of pathology. Therefore, complementary therapy is needed. Our experiments were performed in rats to evaluate the contribution of the purinergic system, especially P2X4 receptor (P2X4R), in the modulation of glia activation and, ...

Microglia in the dorsal horn of the spinal cord are increasingly recognized as being crucial in the pathogenesis of pain hypersensitivity after injury to a peripheral nerve. It is known that P2X4 purinoceptors (P2X4Rs) cause the release of brain-derived neurotrophic factor (BDNF) from microglia, which is necessary for maintaining pain hypersensitivity after nerve injury. However, there is a cri...

The P2X4 receptor is a cation-selective channel capable of permeating Na+, K+ and Ca2+. Most of the data available refer to the rat P2X4 receptor, which shares a high identity with the mouse P2X4 receptor. The calcium permeability is relatively high; calcium contributes 8% of the total current through the human P2X4 receptor in the presence of 1.8 mM extracellular calcium. When the ligand ATP i...