Nicotinic acetylcholine receptors (nAChRs) are actively being investigated as therapeutic targets for the treatment of pain and inflammation, but despite more than 30 years of research, there are ...currently no FDA‐approved analgesics that are specific for these receptors. Much of the initial research effort focused on the α4β2 nAChR subtype, but more recently, additional subtypes have been identified as promising new leads and include α6β4, α7, and α9‐containing nAChRs. This Review will focus on the distribution of these nAChRs in the cell types involved in neuropathic pain and inflammation and the activity of currently available nicotinic ligands.
Nicotinic acetylcholine receptors (nAChRs) have been historically defined as ligand-gated ion channels and function as such in the central and peripheral nervous systems. Recently, however, non-ionic ...signaling mechanisms via nAChRs have been demonstrated in immune cells. Furthermore, the signaling pathways where nAChRs are expressed can be activated by endogenous ligands other than the canonical agonists acetylcholine and choline. In this review, we discuss the involvement of a subset of nAChRs containing α7, α9, and/or α10 subunits in the modulation of pain and inflammation via the cholinergic anti-inflammatory pathway. Additionally, we review the most recent advances in the development of novel ligands and their potential as therapeutics.
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Two-dimensional (2D) materials are not expected to be metals at low temperature owing to electron localization1. Consistent with this, pioneering studies on thin lms reported only superconducting and ...insulating ground states, with a direct transition between the two as a function of disorder or magnetic eld26. However, more recent works have revealed the presence of an intermediate quantum metallic state occupying a substantial region of the phase diagram710, whose nature is intensely debated1117. Here, we observe such a state in the disorder-free limit of a crystalline 2D superconductor, produced by mechanical co-lamination of NbSe2 in an inert atmosphere. Under a small perpendicular magnetic eld, we induce a transition from superconductor to the quantum metal. We nd a unique power-law scaling with eld in this phase, which is consistent with the Bose-metal model where metallic behaviour arises from strong phase uctuations caused by the magnetic field1114.
The distinct Landau level spectrum of bilayer graphene (BLG) is predicted to support a non-abelian even-denominator fractional quantum Hall (FQH) state similar to the
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state first identified in ...GaAs. However, the nature of this state has remained difficult to characterize. Here, we report transport measurements of a robust sequence of even-denominator FQH in dual-gated BLG devices. Parallel field measurement confirms the spin-polarized nature of the ground state, which is consistent with the Pfaffian/anti-Pfaffian description. The sensitivity of the even-denominator states to both filling fraction and transverse displacement field provides new opportunities for tunability. Our results suggest that BLG is a platform in which topological ground states with possible non-abelian excitations can be manipulated and controlled.
Neuropathic pain is a complex and debilitating syndrome for which there are few effective pharmacological treatments. Opioid‐based medications are initially effective for acute pain, but tolerance to ...their analgesic effects quickly develops, and long‐term use often leads to physical dependence and addiction. Furthermore, neuropathic pain is generally resistant to non‐steroidal anti‐inflammatory drugs. Other classes of medications including antidepressants, antiepileptics and voltage‐gated calcium channel inhibitors are only partially effective in most patients, may be associated with significant side effects and have few disease‐modifying effects on the underlying pathology. Medications that act through new mechanisms of action, and particularly ones that have disease‐modifying properties, would be highly desirable. In the last decade, a potential new target for the treatment of neuropathic pain has emerged: the α9‐containing nicotinic acetylcholine receptor (nAChR). Recent studies indicate that antagonists of α9‐containing nAChRs are analgesic in animal models of neuropathic pain. These nerve injury models include chronic constriction injury, partial sciatic nerve ligation, streptozotocin‐induced diabetic neuropathy and chemotherapeutic‐induced neuropathy. This review details the history and state of the field regarding the role that α9‐containing nAChRs may play in neuropathic pain. An alternative hypothesis that α‐conotoxins exert their therapeutic effect through blocking N‐type calcium channels via activation of GABAB receptors is also reviewed. Understanding how antagonists of α9‐containing nAChRs exert their therapeutic effects may ultimately result in the development of medications that not only treat but also prevent the development of neuropathic pain states.
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This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc
The unique linear and massless band structure of graphene in a purely two-dimensional Dirac fermionic structure has led to intense research in fields ranging from condensed matter physics to ...nanoscale device applications covering the electrical, thermal, mechanical and optical domains. Here, we report three consecutive first observations in graphene-silicon hybrid optoelectronic devices--ultralow-power resonant optical bistability, self-induced regenerative oscillations and coherent four-wave mixing--all at few-femtojoule cavity recirculating energies. These observations, in comparison with control measurements on solely monolithic silicon cavities, are enabled only by the dramatically large and ultrafast χ(3) nonlinearities in graphene and the large Q/V ratios in wavelength-localized photonic crystal cavities. These third-order nonlinear results demonstrate the feasibility and versatility of hybrid two-dimensional graphene-silicon nanophotonic devices for next-generation chip-scale high-speed optical communications, radiofrequency optoelectronics and all-optical signal processing.
Heterostructures based on layering of two-dimensional (2D) materials such as graphene and hexagonal boron nitride represent a new class of electronic devices. Realizing this potential, however, ...depends critically on the ability to make high-quality electrical contact. Here, we report a contact geometry in which we metalize only the ID edge of a 2D graphene layer. In addition to outperforming conventional surface contacts, the edge-contact geometry allows a complete separation of the layer assembly and contact metallization processes. In graphene heterostructures, this enables high electronic performance, including low-temperature ballistic transport over distances longer than 15 micrometers, and room-temperature mobility comparable to the theoretical phonon-scattering limit. The edge-contact geometry provides new design possibilities for multilayered structures of complimentary 2D materials.
We report on an experimental measurement of Coulomb drag in a double quantum well structure consisting of bilayer-bilayer graphene, separated by few layer hexagonal boron nitride. At low temperatures ...and intermediate densities, a novel negative drag response with an inverse sign is observed, distinct from the momentum and energy drag mechanisms previously reported in double monolayer graphene. By varying the device aspect ratio, the negative drag component is suppressed and a response consistent with pure momentum drag is recovered. In the momentum drag dominated regime, excellent quantitative agreement with the density and temperature dependence predicted for double bilayer graphene is found.
The success of metal-based plasmonics for manipulating light at the nanoscale has been empowered by imaginative designs and advanced nano-fabrication. However, the fundamental optical and electronic ...properties of elemental metals, the prevailing plasmonic media, are difficult to alter using external stimuli. This limitation is particularly restrictive in applications that require modification of the plasmonic response at sub-picosecond timescales. This handicap has prompted the search for alternative plasmonic media, with graphene emerging as one of the most capable candidates for infrared wavelengths. Here we visualize and elucidate the properties of non-equilibrium photo-induced plasmons in a high-mobility graphene monolayer. We activate plasmons with femtosecond optical pulses in a specimen of graphene that otherwise lacks infrared plasmonic response at equilibrium. In combination with static nano-imaging results on plasmon propagation, our infrared pump-probe nano-spectroscopy investigation reveals new aspects of carrier relaxation in heterostructures based on high-purity graphene.
A spatially indirect exciton is created when an electron and a hole, confined to separate layers of a double quantum well system, bind to form a composite boson. Such excitons are long-lived, and in ...the limit of strong interactions are predicted to undergo a Bose-Einstein condensate-like phase transition into a superfluid ground state. Here, we report evidence of an exciton condensate in the quantum Hall effect regime of double-layer structures of bilayer graphene. Interlayer correlation is identified by quantized Hall drag at matched layer densities, and the dissipationless nature of the phase is confirmed in the counterflow geometry. A selection rule for the condensate phase is observed involving both the orbital and valley indices of bilayer graphene. Our results establish double bilayer graphene as an ideal system for studying the rich phase diagram of strongly interacting bosonic particles in the solid state.
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