Involvement of lysophosphatidic acid in bone cancer pain by potentiation of TRPV1 via PKCϵ pathway in dorsal root ganglion neurons

<p>Abstract</p> <p>Background</p> <p>It has been demonstrated that lysophosphatidic acid (LPA) released from injury tissue and transient receptor potential vanilloid 1 (TRPV1) receptor are implicated in the induction of chronic pain. In the present study we examined whether an interaction between LPA receptor LPA₁and TRPV1 in dorsal root ganglion (DRG) neurons contributes to the development of bone cancer pain.</p> <p>Results</p> <p>Bone cancer was established by injection of mammary gland carcinoma cells into the rat tibia. Following the development of bone cancer pain, the TRPV1 expression and capsaicin-evoked currents were up-regulated in rat DRG neurons at L_4-6segments. Immunohistochemistry staining revealed a high co-localization of LPA₁with TRPV1 in DRG neurons. In isolated DRG neurons, whole-cell patch recording showed that capsaicin-induced currents were potentiated by LPA in a dose-dependent manner. The potentiation was blocked by either LPA₁antagonist, protein kinase C (PKC) inhibitor or PKCϵ inhibitor, but not by protein kinase A (PKA) inhibitor or Rho inhibitor. In the behavioral tests, both mechanical allodynia and thermal hyperalgesia in bone cancer rats were attenuated by LPA₁antagonist.</p> <p>Conclusion</p> <p>LPA potentiates TRPV1 current via a PKCϵ-dependent pathway in DRG neurons of rats with bone cancer, which may be a novel peripheral mechanism underlying the induction of bone cancer pain.</p

URLLC packet management for packetized predictive control

Packetized predictive control (PPC) is an effective solution to ensure the robustness of the control system over unreliable wireless links. However, conventional wireless transmission methods in PPC suffer from either high wireless resource consumption or poor performance of real-time control due to the separately design of the two parts. To deal with the issue, we propose a communicationcontrol co-design approach to achieve good trade-off between real-time control performance and communication energy efficiency. Our results demonstrate the advantages of the communication-control co-design

In-situ cosmogenic ³⁶Cl denudation rates of carbonates in Guizhou karst area

This study quantifies surface denudation of carbonate rocks by the first application of in-situ cosmogenic &lt;sup&gt;36&lt;/sup&gt;Cl in China. Concentrations of natural Cl and in-situ cosmogenic &lt;sup&gt;36&lt;/sup&gt;Cl in bare carbonates from Guizhou karst areas were measured with isotope dilution by accelerator mass spectrometer. The Cl concentration varied from 16 to 206 ppm. The &lt;sup&gt;36&lt;/sup&gt;Cl concentrations were in range of (0.8–2.4)×106 atom g−1, resulting in total denudation rates of 20–50 mm ka−1 that averaged over a 104–105 a timescale. The &lt;sup&gt;36&lt;/sup&gt;Cl-denudation rates showed roughly a negative correlation with the local mean temperature. This preliminary observation may suggest the variations of proportions of chemical weathering and physical erosion in denudation process, depending upon local climatic conditions

Ryanodine receptors contribute to the induction of nociceptive input-evoked long-term potentiation in the rat spinal cord slice

<p>Abstract</p> <p>Background</p> <p>Our previous study demonstrated that nitric oxide (NO) contributes to long-term potentiation (LTP) of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cord <it>in vivo</it>. Ryanodine receptor (RyR) is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway.</p> <p>Results</p> <p>By means of field potential recordings in the adult male rat <it>in vivo</it>, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT) stably induced LTP of field excitatory postsynaptic potentials (fEPSPs). Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5)P3 receptor (IP₃R) antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs). Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG) neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca²⁺]_iin small DRG neurons.</p> <p>Conclusions</p> <p>These data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.</p