Psilocybin has no immediate or persistent analgesic effect in acute and chronic mouse pain models.

The psychedelic psilocybin may have lasting therapeutic effects for patients with chronic pain syndromes. Some clinical and preclinical data suggest these putative benefits derive from direct analgesic effects. However, this possibility has not been comprehensively tested in preclinical models.

Ketamine Evokes Acute Behavioral Effects Via μ Opioid Receptor-Expressing Neurons of the Central Amygdala.

Background: Ketamine has anesthetic, analgesic, and antidepressant properties, which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. This mechanism may differentiate ketamine from other NMDA receptor antagonists.

Statistical learning shapes pain perception and prediction independently of external cues.

The placebo and nocebo effects highlight the importance of expectations in modulating pain perception, but in everyday life we don't need an external source of information to form expectations about pain. The brain can learn to predict pain in a more fundamental way, simply by experiencing fluctuating, non-random streams of noxious inputs, and extracting their temporal regularities. This process is called statistical learning.

Opioid receptor expressing neurons of the central amygdala gate behavioral effects of ketamine in mice.

Ketamine has anesthetic, analgesic, and antidepressant properties which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. It is unclear whether naltrexone blocks a direct effect of ketamine at ORs, or whether normal functioning of the OR system is required to realize the full antidepressant effects of treatment.

Brief lifestyle interventions for prediabetes in primary care: a service evaluation.

Background: The increasing number of cases of prediabetes in the UK is concerning, particularly in Wales where there is no standard programme of support. The aim of the current service evaluation was to examine the effectiveness of brief lifestyle interventions on glucose tolerance in people at risk of developing type 2 diabetes.

Methods: In this pragmatic service evaluation clinical data on people deemed at risk of developing type 2 diabetes were evaluated from two GP clusters.

A Standardized Strategy for Simultaneous Quantification of Urine Metabolites to Validate Development of a Biomarker Panel Allowing Comprehensive Assessment of Dietary Exposure.

Scope: Metabolites derived from individual foods found in human biofluids after consumption could provide objective measures of dietary intake. For comprehensive dietary assessment, quantification methods would need to manage the structurally diverse mixture of target metabolites present at wide concentration ranges.

Methods And Results: A strategy for selection of candidate dietary exposure biomarkers is developed.

Peripheral Nerve Stimulation for Pudendal Neuralgia: A Technical Note.

Background: Pudendal neuropathy is a chronic, disabling form of perineal pain that involves the pudendal nerve, a mixed somatic and autonomic nerve that originates from sacral nerve roots. Peripheral nerve stimulation of the pudendal nerve can be useful to decrease symptom burden in patients who have failed initial conservative treatment modalities.

Methods: In this manuscript, we describe an approach to the placement of a peripheral nerve stimulator for the treatment of pudendal neuralgia.

P2X4 Receptors on Muscle Macrophages Are Required for Development of Hyperalgesia in an Animal Model of Activity-Induced Muscle Pain.

Activity-induced pain is common in those with chronic musculoskeletal pain and limits participation in daily activities and exercise. Our laboratory developed a model of activity-induced pain and shows that depletion of muscle macrophages prevents development of hyperalgesia. Adenosine triphosphate (ATP) is released from fatiguing muscle and activates purinergic receptors (P2X), and P2X4 receptors are expressed on macrophages.

No Influence of Low-, Medium-, or High-Dose Tyrosine on Exercise in a Warm Environment.

Purpose: Tyrosine administration may counter exercise fatigue in a warm environment, but the typical dose is inconclusive, with little known about higher doses. We explored how three tyrosine doses influenced the circulating ratio of tyrosine/amino acids competing for brain uptake and hypothesized that a medium and high dose would enhance exercise performance in a warm environment.

Methods: Eight recreationally trained, non-heat-acclimated male individuals (mean ± SD age, 23 ± 4 yr; stature, 181 ± 7 cm; body mass, 76.

Acid Sensing Ion Channel 1a (ASIC1a) Mediates Activity-induced Pain by Modulation of Heteromeric ASIC Channel Kinetics.

Chronic muscle pain is acutely worsened by exercise. Acid sensing ion channels (ASIC) are heteromeric channels expressed in muscle sensory neurons that detect decreases in pH. We have previously shown ASIC3 is important in activity-induced hyperalgesia.

Reduced Arch Length as a Factor for 4-Implant Immediate Function in the Maxilla: A Technical Note and Report of 39 Patients Followed for 5 Years.

Purpose: To determine whether maxillary arch length deficiency treated with a V-4 implant placement method is adequate for immediate functional loading during a 5-year follow-up.

Materials And Methods: Thirty-nine patients were treated with maxillary immediate function from January 3, 2011 to February 28, 2011 and followed for a period of 5 years. Arch length after implant placement was measured retrospectively around the arch from the anterior sinus wall to the contralateral anterior sinus wall in a mid-alveolar arc on the occlusal view of the preoperative computed tomogram.

Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats.

Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans.

Regular physical activity prevents chronic pain by altering resident muscle macrophage phenotype and increasing interleukin-10 in mice.

Regular physical activity in healthy individuals prevents development of chronic musculoskeletal pain; however, the mechanisms underlying this exercise-induced analgesia are not well understood. Interleukin-10 (IL-10), an antiinflammatory cytokine that can reduce nociceptor sensitization, increases during regular physical activity. Since macrophages play a major role in cytokine production and are present in muscle tissue, we propose that physical activity alters macrophage phenotype to increase IL-10 and prevent chronic pain.

The dichotomized role for acid sensing ion channels in musculoskeletal pain and inflammation.

Chronic muscle pain affects between 11 and 24% of the world's population with the majority of people experiencing musculoskeletal pain at some time in their life. Acid sensing ion channels (ASICs) are important sensors of modest decreases in extracellular pH that occur within the physiological range. These decreases in extracellular pH occur in response to inflammation, fatiguing exercise, and ischemia.

ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia.

An acute bout of exercise can exacerbate pain, hindering participation in regular exercise and daily activities. The mechanisms underlying pain in response to acute exercise are poorly understood. We hypothesized that proton accumulation during muscle fatigue activates acid-sensing ion channel 3 (ASIC3) on muscle nociceptors to produce hyperalgesia.

Anatomical and physiological factors contributing to chronic muscle pain.

Chronic muscle pain remains a significant source of suffering and disability despite the adoption of pharmacologic and physical therapies. Muscle pain is mediated by free nerve endings distributed through the muscle along arteries. These nerves project to the superficial dorsal horn and are transmitted primarily through the spinothalamic tract to several cortical and subcortical structures, some of which are more active during the processing of muscle pain than other painful conditions.

An overview of animal models of pain: disease models and outcome measures.

Unlabelled: Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined.

Fatigue-enhanced hyperalgesia in response to muscle insult: induction and development occur in a sex-dependent manner.

Chronic muscle pain affects 20-50% of the population, is more common in women than men, and is associated with increased pain during physical activity and exercise. Muscle fatigue is common in people with chronic muscle pain, occurs in response to exercise, and is associated with release of fatigue metabolites. Fatigue metabolites can sensitize muscle nociceptors, which could enhance pain with exercise.