- Pain Mechanisms and Treatments
- Nerve injury and regeneration
- Neuropeptides and Animal Physiology
- Ion channel regulation and function
- Peripheral Nerve Disorders
- Transcranial Magnetic Stimulation Studies
- Pain Management and Placebo Effect
- Botulinum Toxin and Related Neurological Disorders
- Hereditary Neurological Disorders
- Neurobiology and Insect Physiology Research
- Ion Channels and Receptors
- Genetic Neurodegenerative Diseases
- Peripheral Neuropathies and Disorders
- Muscle activation and electromyography studies
- Neuroscience and Neuropharmacology Research
- Olfactory and Sensory Function Studies
- Pain Management and Opioid Use
- Anesthesia and Pain Management
- Musculoskeletal pain and rehabilitation
- Neuroscience and Neural Engineering
- Thermoregulation and physiological responses
- Neurogenesis and neuroplasticity mechanisms
- Cancer Treatment and Pharmacology
- Amyotrophic Lateral Sclerosis Research
- Neurological disorders and treatments
National Hospital for Neurology and Neurosurgery
2016-2025
University College London
2016-2025
Neurosciences Institute
2021
University College London Hospitals NHS Foundation Trust
2018-2019
Sobell House
2010-2017
Spinal Research
2017
MRC Prion Unit
2010-2014
Medical Research Council
2011-2013
Oxford University Hospitals NHS Trust
2012
Institute of Child Health
2012
The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the “pain” pathway. Heterologously can be activated vanilloid compounds, protons, or heat (>43°C), but whether this contributes to chemical thermal sensitivity in vivo not known. Here, we demonstrate that from mice lacking are severely deficient their responses each these noxious stimuli. −/− showed normal mechanical stimuli exhibited no vanilloid-evoked pain behavior, were impaired...
RNA amplification is necessary for profiling gene expression from small tissue samples. Previous studies have shown that the T7 based techniques are reproducible but may distort true abundance of targets. However, consequences such distortions on ability to detect biological variation in not been explored sufficiently define extent usability and limitations techniques. We show ratios occasionally distorted by using Affymetrix sample protocol version 2 due a disproportional shift intensity...
1. We examined the functional properties of unmyelinated primary afferent neurones innervating pelvic viscera in twenty‐five anaesthetized cats. The axons were isolated from intact dorsal root and or chronically de‐efferented ventral segment S2. All units electrically identified with electrical stimulation nerve. 2. responses studied natural urinary bladder using innocuous noxious increases intravesical pressure at onset an acute artificial inflammation induced by intraluminal injection...
The principle finding of the present study is that there are two types mechanical hyperalgesia developing in human hairy skin following injurious stimuli. Mechanical comprises a dynamic component (brush-evoked pain, allodynia) signalled by large myelinated afferents and static (hyperalgesia to pressure stimuli) unmyelinated afferents. While only found injured area, also extends into halo undamaged tissue surrounding injury. irritant chemicals, mustard oil or capsaicin, were applied...
Brush-evoked pain (mechanical allodynia, dynamic mechanical hyperalgesia) is a hallmark of neuropathic and inflammatory states. Here we have examined the neural mechanisms that induce maintain this component hyperalgesis. The principle finding these experiments severity brush-evoked correlates with intensity backgound in patients suffering from chronic painful neuropathies normal subjkects acute experimental chemogenic pain. In on nine subjects topical application mustrard oil for 5 min...
Nerve growth factor (NGF) was originally discovered as a neurotrophic essential for the survival of sensory and sympathetic neurons during development. However, in adult NGF has been found to play an important role nociceptor sensitization after tissue injury. The authors outline mechanisms by which activation its cognate receptor, tropomyosin-related kinase A regulates host ion channels, receptors, signaling molecules enhance acute chronic pain. also document that peripherally restricted...
Voltage-gated sodium (Na(V)1) channels play a critical role in modulating the excitability of sensory neurons, and human genetic evidence points to Na(V)1.7 as an essential contributor pain signaling. Human loss-of-function mutations SCN9A, gene encoding Na(V)1.7, cause channelopathy-associated indifference (CIP), whereas gain-of-function are associated with two inherited painful neuropathies. Although data make attractive target for development analgesics, pharmacological proof-of-concept...
Using an in vitro nerve skin preparation and controlled mechanical or thermal stimuli, we analyzed the receptive properties of 277 mechanosensitive single primary afferents with myelinated (n = 251) unmyelinated 26) axons innervating hairy adult 2-wk-old mice. Afferents were recorded from small filaments either sural saphenous nerves outbred mice strain inbred Balb/c strain. On basis their conduction velocity, several receptor types could be distinguished. In animals (>6 wk old), 54% large...
Different types of hyperalgesia were studied after experimental induction inflammation in small skin areas healthy volunteers either by topical application capsaicin solution (1% 70% ethanol) or briefly freezing a area similar size to -28 degrees C. Sensory tests performed 30 min and 22 h freeze lesions. Heat pain thresholds lowered both treatments, probably due nociceptor sensitization. Hyperalgesia four mechanical stimulation was studied. (i) punctate stimuli encountered at the site...
Vanilloid receptor 1 (TRPV1) has been proposed to be the principal heat-responsive channel for nociceptive neurons. The skin of both rat and mouse receives major projections from primary sensory afferents that bind plant lectin isolectin B4 (IB4). majority IB4-positive neurons are known nociceptors. Previous studies suggested that, unlike rat, cutaneous did not express TRPV1 immunoreactivity. Here, multiple antisera were used confirm have different distributions immunoreactivity is absent in...