Modification of neuropathic pain sensation through microglial ATP receptors

Neuropathic pain that typically develops when peripheral nerves are damaged through surgery, bone compression in cancer, diabetes, or infection is a major factor causing impaired quality of life in millions of people worldwide. Recently, there has been a rapidly growing body of evidence indicating that spinal glia play a critical role in the pathogenesis of neuropathic pain. Accumulating findings also indicate that nucleotides play an important role in neuron-glia communication through P2 purinoceptors. Damaged neurons release or leak nucleotides including ATP and UTP to stimulate microglia through P2 purinoceptors expressing on microglia. It was shown in an animal model of neuropathic pain that microglial P2X4 and P2X7 receptors are crucial in pain signaling after peripheral nerve lesion. In this review, we describe the modification of neuropathic pain sensation through microglial P2X4 and P2X7, with the possibility of P2Y6 and P2Y12 involvement

P2 receptors and chronic pain

There is abundant evidence that extracellular ATP and other nucleotides have an important role in pain signaling at both the periphery and in the CNS. The focus of attention now is on the possibility that endogenous ATP and its receptor system might be activated in chronic pathological pain states, particularly in neuropathic and inflammatory 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 receptors, particularly the P2X4, P2X3 and P2X7 receptors, in neuropathic and inflammatory pain. The expression of P2X4 receptors in the spinal cord is enhanced in spinal microglia after peripheral nerve injury, and blocking pharmacologically and suppressing molecularly P2X4 receptors produce a reduction of the neuropathic pain behaviour. Understanding the key roles of these ATP receptors may lead to new strategies for the management of intractable chronic pain

Local Soft Tissue Compression Enhances Fracture Healing in a Rabbit Fibula

Local soft tissue compression of fractures enhances fracture healing. The mechanism remains uncertain. Past studies have focused on intermittent soft tissue compression. We report a preliminary study assessing the relationship between constant soft tissue compression and enhanced fracture healing in an osteotomy model designed to minimize confounding variables. Fibulae of nine New Zealand white rabbits were bilaterally osteotomized, openly stabilized, and fitted with spandex stockinets. Soft tissue at the osteotomy site was unilaterally compressed using a deforming element (load = 26 mmHg). The contralateral side was saved as the control and was not compressed. Osteotomies were monitored with weekly radiographs. All fibulae in both groups were healed 6 weeks postoperatively. Micro-CT analysis of bone mineral density (BMD) and bone volume (BV) was then performed on both the experimental and control sides. Radiographic measurement of transverse callus-to-shaft ratios (TCSR) was compared. BMD of the experimental callus was greater than the noncompressed controls. BV and TCSR were not different between controls and experimental osteotomies. Constant local soft tissue compression produced significant increases in BMD, but not in BV or transverse callus size, indicating significant measurable increases in callus composition without significant change in gross dimensions. Our experimental design minimizes confounding factors, such as micromotion, immobilization, and altered venous flow, suggesting that these are not the primary mechanisms for fracture healing enhancement. Further studies with more animals and study groups are necessary to confirm efficacy and identify optimal compression pressures and schedules

A near-infrared fluorophore for live-cell super-resolution microscopy of cellular proteins

The ideal fluorescent probe for bioimaging is bright, absorbs at long wavelengths and can be implemented flexibly in living cells and in vivo. However, the design of synthetic fluorophores that combine all of these properties has proved to be extremely difficult. Here, we introduce a biocompatible near-infrared silicon-rhodamine probe that can be coupled specifically to proteins using different labelling techniques. Importantly, its high permeability and fluorogenic character permit the imaging of proteins in living cells and tissues, and its brightness and photostability make it ideally suited for live-cell super-resolution microscopy. The excellent spectroscopic properties of the probe combined with its ease of use in live-cell applications make it a powerful new tool for bioimaging.\ua9 2013 Macmillan Publishers Limited. All rights reserved