Ca2+ channel α2δ1 protein in spinal neuron sensitization

BackgroundVoltage-gated calcium channel α2 δ1 subunit is the binding site for gabapentin, an effective drug in controlling neuropathic pain states including thermal hyperalgesia. Hyperalgesia to noxious thermal stimuli in both spinal nerve-ligated (SNL) and voltage-gated calcium channel α2 δ1 overexpressing transgenic (Tg) mice correlates with higher α2 δ1 levels in dorsal root ganglia and dorsal spinal cord. In this study, we investigated whether abnormal synaptic transmission is responsible for thermal hyperalgesia induced by elevated α2 δ1 expression in these models.MethodsBehavioural sensitivities to thermal stimuli were test in L4 SNL and sham mice, as well as in α2 δ1 Tg and wild-type mice. Miniature excitatory (mEPSC) and inhibitory (mIPSC) post-synaptic currents were recorded in superficial dorsal spinal cord neurons from these models using whole-cell patch clamp slice recording techniques.ResultsThe frequency, but not amplitude, of mEPSC in superficial dorsal horn neurons was increased in SNL and α2 δ1 Tg mice, which could be attenuated by gabapentin dose dependently. Intrathecal α2 δ1 antisense oligodeoxynucleotide treatment diminished increased mEPSC frequency and gabapentin's inhibitory effects in elevated mEPSC frequency in the SNL mice. In contrast, neither the frequency nor the amplitude of mIPSC was altered in superficial dorsal horn neurons from the SNL and α2 δ1 Tg mice.ConclusionsOur findings support a role of peripheral nerve injury-induced α2 δ1 in enhancing pre-synaptic excitatory input onto superficial dorsal spinal cord neurons that contributes to nociception development

Spinal GABA mechanism in neuropathic pain after spinal cord injury

Spinal cord injury (SCI) often causes sensitization of spinal dorsal horn excitatory neurons via disruption of inhibitory output that results in exaggerated nociceptive transmission. Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter and thought to be critical for spinal inhibitory synaptic transmission. However, SCI causes hypofunctional GABAergic inhibitory output via multiple mechanisms, including loss of GABAergic neurons, downregulation of GABA synthesis enzymes, decrease of primary afferent innervation into GABAergic neurons, and shifts of Cl− gradient in the spinal dorsal horn. These disruptions of GABAergic inhibitory output critically contribute to neuronal hyperexcitability in the spinal dorsal horn and chronic neuropathic pain states following SCI. In this book chapter, we focus on spinal GABAergic mechanisms of chronic neuropathic pain development following SCI in rodent animals

A space-time continuous finite element method for 2D viscoelastic wave equation

International audienceA widespread approach to software service analysis uses session types. Very different type theories for binary and multiparty protocols have been developed; establishing precise connections between them remains an open problem. We present the first formal relation between two existing theories of binary and multiparty session types: a binary system rooted in linear logic, and a multiparty system based on automata theory. Our results enable the analysis of multiparty protocols using a (much simpler) type theory for binary protocols, ensuring protocol fidelity and deadlock-freedom. As an application, we offer the first theory of multiparty session types with behavioral genericity. This theory is natural and powerful; its analysis techniques reuse results for binary session types

Weaker land–climate feedbacks from nutrient uptake during photosynthesis-inactive periods

Terrestrial carbon–climate feedbacks depend on two large and opposing fluxes—soil organic matter decomposition and photosynthesis—that are tightly regulated by nutrients . Earth system models (ESMs) participating in the Coupled Model Intercomparison Project Phase 5 represented nutrient dynamics poorly , rendering predictions of twenty-first century carbon–climate feedbacks highly uncertain. Here, we use a new land model to quantify the effects of observed plant nutrient uptake mechanisms missing in most other ESMs. In particular, we estimate the global role of root nutrient competition with microbes and abiotic processes during periods without photosynthesis. Nitrogen and phosphorus uptake during these periods account for 45 and 43%, respectively, of annual uptake, with large latitudinal variation. Globally, night-time nutrient uptake dominates this signal. Simulations show that ignoring this plant uptake, as is done when applying an instantaneous relative demand approach, leads to large positive biases in annual nitrogen leaching (96%) and N O emissions (44%). This N O emission bias has a GWP equivalent of ~2.4 PgCO yr , which is substantial compared to the current terrestrial CO sink. Such large biases will lead to predictions of overly open terrestrial nutrient cycles and lower carbon sequestration capacity. Both factors imply over-prediction of positive terrestrial feedbacks with climate in current ESMs. 1,2 1,3 −1 2 2 2

Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV

The inclusive cross section for production of isolated photons has been measured in \pbarp collisions at $\sqrt{s} = 630$ GeV with the \D0 detector at the Fermilab Tevatron Collider. The photons span a transverse energy ($E_T$) range from 7-49 GeV and have pseudorapidity $|\eta| < 2.5$. This measurement is combined with to previous \D0 result at $\sqrt{s} = 1800$ GeV to form a ratio of the cross sections. Comparison of next-to-leading order QCD with the measured cross section at 630 GeV and ratio of cross sections show satisfactory agreement in most of the $E_T$ range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001