The Retinal Nerve Fiber Layer Thickness Is Associated with Systemic Neurodegeneration in Long-Term Type 1 Diabetes.

Purpose: To determine whether the retinal nerve fiber layer thickness can be used as an indicator for systemic neurodegeneration in diabetes.

Methods: We used existing data from 38 adults with type 1 diabetes and established polyneuropathy. Retinal nerve fiber layer thickness values of four scanned quadrants (superior, inferior, temporal, and nasal) and the central foveal thickness were extracted directly from optical coherence tomography.

Palpebral Fissure Response to Phenylephrine Indicates Autonomic Dysfunction in Patients With Type 1 Diabetes and Polyneuropathy.

Purpose: The superior and inferior tarsal muscles are sympathetically innervated smooth muscles. Long-term diabetes often leads to microvascular complications, such as, retinopathy and autonomic neuropathy. We hypothesized that diabetes induces (1) sympathetic paresis in the superior and inferior tarsal muscles and that this measure is associated with (2) the severity of diabetic retinopathy, (3) the duration of diabetes, and (4) autonomic function.

The Role of TRP Channels in Nicotinic Provoked Pain and Irritation from the Oral Cavity and Throat: Translating Animal Data to Humans.

Tobacco smoking-related diseases are estimated to kill more than 8 million people/year and most smokers are willing to stop smoking. The pharmacological approach to aid smoking cessation comprises nicotine replacement therapy (NRT) and inhibitors of the nicotinic acetylcholine receptor, which is activated by nicotine. Common side effects of oral NRT products include hiccoughs, gastrointestinal disturbances and, most notably, irritation, burning and pain in the mouth and throat, which are the most common reasons for premature discontinuation of NRT and termination of cessation efforts.

Psychophysical and vasomotor evidence for interdependency of TRPA1 and TRPV1-evoked nociceptive responses in human skin: an experimental study.

The TRPA1 and TRPV1 receptors are important pharmaceutical targets for antipruritic and analgesic therapy. Obtaining further knowledge on their roles and interrelationship in humans is therefore crucial. Preclinical results are contradictory concerning coexpression and functional interdependency of TRPV1 and TRPA1, but no human evidence exists.

Altered Central Sensitization and Pain Modulation in the CNS in Chronic Joint Pain.

Musculoskeletal pain disorders are the second largest contributor to global disability underlining the significance of effective treatments. However, treating chronic musculoskeletal pain, and chronic joint pain (osteoarthritis (OA)) in particular, is challenging as the underlying peripheral and central pain mechanisms are not fully understood, and safe and efficient analgesic drugs are not available. The pain associated with joint pain is highly individual, and features from radiological imaging have not demonstrated robust associations with the pain manifestations.

Chronic postoperative pain after primary and revision total knee arthroplasty.

Objectives: Clinical experience suggests that patients with osteoarthritis (OA) undergoing revision total knee arthroplasty (TKA) experience more chronic complications after surgery compared with patients receiving primary TKA. This study aimed to investigate the difference in pain, mobility, and quality of life (QoL) in patients after revision TKA compared with patients after primary TKA.

Methods: A total of 99 OA patients after revision TKA surgery and 215 patients after primary TKA surgery were investigated in a cross-sectional study using: a pain description of current pain (non-existent, mild, moderate, severe, or unbearable), the pain intensity visual analogue scale, the Knee Society Score, and the Osteoarthritis Research Society International questionnaire.

Motor inhibition affects the speed but not accuracy of aimed limb movements in an insect.

When reaching toward a target, human subjects use slower movements to achieve higher accuracy, and this can be accompanied by increased limb impedance (stiffness, viscosity) that stabilizes movements against motor noise and external perturbation. In arthropods, the activity of common inhibitory motor neurons influences limb impedance, so we hypothesized that this might provide a mechanism for speed and accuracy control of aimed movements in insects. We recorded simultaneously from excitatory leg motor neurons and from an identified common inhibitory motor neuron (CI1) in locusts that performed natural aimed scratching movements.

Translational pain biomarkers in the early development of new neurotherapeutics for pain management.

Translation of the analgesic efficacy of investigational neurotherapeutics from pre-clinical pain models into clinical trial phases is associated with a high risk of failure. Application of human pain biomarkers in early stages of clinical trials can potentially enhance the rate of successful translation, which would eventually reduce both length and costs of drug development after the pre-clinical stage. Human pain biomarkers are based on the standardized activation of pain pathways followed by the assessment of ongoing and paroxysmal pain, plus evoked responses which can be applied to healthy individuals and patients prior to and after pharmacological interventions.

The UVB cutaneous inflammatory pain model: a reproducibility study in healthy volunteers.

Background: The human ultraviolet-B (UVB) experimental pain model induces cutaneous neurogenic inflammation, involves hyperalgesia, and is widely used as a pharmacological screening pain model.

Aim: To estimate the test-retest reliability of the UVB pain model by application of a comprehensive set of vasomotor and quantitative sensory assessment methods and to estimate sample sizes required for parallel or crossover pharmacological screening studies when this model is considered to be applied.

Methods: The upper arms of 15 healthy male volunteers were UVB irradiated with three times the minimal erythema dose.

The effect of topical capsaicin-induced sensitization on heat-evoked cutaneous vasomotor responses.

Brief, localized, cutaneous, non-painful thermal stimuli can evoke a transient vasomotor response, causing increased cutaneous blood flow and elevated skin temperature. The aims of this study were to investigate 1) if cutaneous sensitization by topical application of capsaicin (TRPV1 receptor agonist) can facilitate the size, duration and spatial extent of this vasomotor response and 2) if males and females respond differently. Thermal pulses (43°C for 60 seconds) were applied on left/right volar forearms of 15 age-matched males and females.

A formal mathematical framework for physiological observations, experiments and analyses.

Experiments can be complex and produce large volumes of heterogeneous data, which make their execution, analysis, independent replication and meta-analysis difficult. We propose a mathematical model for experimentation and analysis in physiology that addresses these problems. We show that experiments can be composed from time-dependent quantities, and be expressed as purely mathematical equations.

Desensitization properties of AMPA receptors at the cerebellar mossy fiber granule cell synapse.

Native AMPA receptors (AMPARs) exhibit rapid and profound desensitization in the sustained presence of glutamate. Desensitization therefore contributes to short-term depression at synapses in which glutamate accumulates. At synapses that do not exhibit desensitization-dependent depression, AMPARs are thought to be protected against prolonged or repetitive exposure to synaptically released glutamate.

Rapid vesicular release, quantal variability, and spillover contribute to the precision and reliability of transmission at a glomerular synapse.

The amplitude and shape of EPSC waveforms are thought to be important determinants of information processing and storage in the brain, yet relatively little is known about the origins of EPSC variability or how it affects synaptic signaling. We investigated the stochastic determinants of AMPA receptor-mediated EPSC variability at cerebellar mossy fiber-granule cell (MF-GC) connections by combining multiple-probability fluctuation analysis (MPFA) and deconvolution methods. The properties of MF connections with a single release site and the effects of the rapidly equilibrating competitive antagonist kynurenic acid on EPSCs suggest that receptors are not saturated by glutamate during a quantal event and that quanta sum linearly over a wide range of release probabilities.

Modulation of glutamate mobility reveals the mechanism underlying slow-rising AMPAR EPSCs and the diffusion coefficient in the synaptic cleft.

Fast- and slow-rising AMPA receptor-mediated EPSCs occur at central synapses. Fast-rising EPSCs are thought to be mediated by rapid local release of glutamate. However, two controversial mechanisms have been proposed to underlie slow-rising EPSCs: prolonged local release of transmitter via a fusion pore, and spillover of transmitter released rapidly from distant sites.