A5069163555- Pain Mechanisms and Treatments
- Botulinum Toxin and Related Neurological Disorders
- Hereditary Neurological Disorders
- Ion channel regulation and function
- Ion Channels and Receptors
- Antifungal resistance and susceptibility
- Pain Management and Opioid Use
- Visual perception and processing mechanisms
- Fungal Infections and Studies
- Tactile and Sensory Interactions
- Infectious Diseases and Mycology
- Acupuncture Treatment Research Studies
- Neurological Disorders and Treatments
- Olfactory and Sensory Function Studies
- Pericarditis and Cardiac Tamponade
- Cancer, Stress, Anesthesia, and Immune Response
- Retinal Development and Disorders
- Cardiac tumors and thrombi
- Aesthetic Perception and Analysis
- Alcohol Consumption and Health Effects
- Cannabis and Cannabinoid Research
- Postharvest Quality and Shelf Life Management
- Motor Control and Adaptation
- Signaling Pathways in Disease
- CCD and CMOS Imaging Sensors
University of Oxford
2013-2025
John Radcliffe Hospital
2013-2025
Universidad Internacional SEK
2023
Bennett Aerospace (United States)
2016
King's College London
2012-2014
University College London
2014
Wolfson Foundation
2014
King's College Hospital
2012
Doheny Eye Institute
2010
Universidad de Antioquia
2010
Human monogenic pain syndromes have provided important insights into the molecular mechanisms that underlie normal and pathological states.We describe an autosomal-dominant familial episodic syndrome characterized by episodes of debilitating upper body pain, triggered fasting physical stress.Linkage haplotype analysis mapped this phenotype to a 25 cM region on chromosome 8q12-8q13.Candidate gene sequencing identified point mutation (N855S) in S4 transmembrane segment TRPA1, key sensor for...
In Brief Disabling neuropathic pain (NeuP) is a common sequel of diabetic peripheral neuropathy (DPN). We aimed to characterise the sensory phenotype patients with and without NeuP, assess screening tools for relate DPN severity NeuP. The Pain in Neuropathy Study (PiNS) an observational cross-sectional multicentre study. A total 191 underwent neurological examination, quantitative testing, nerve conduction studies, skin biopsy intraepidermal fibre density assessment. set questionnaires...
Abstract In a recent cluster analysis, it has been shown that patients with peripheral neuropathic pain can be grouped into 3 sensory phenotypes based on quantitative testing profiles, which are mainly characterized by either loss, intact function and mild thermal hyperalgesia and/or allodynia, or loss of detection mechanical allodynia. Here, we present an algorithm for allocation individual to these subgroups. The is nondeterministic—ie, patient sorted more than one phenotype—and separate...
Abstract Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes. Almost half the patients with DPN develop neuropathic pain (NeuP) for which current analgesic treatments are inadequate. Understanding role genetic variability in development painful needed improved understanding pathogenesis better patient stratification clinical trials and to target therapy more appropriately. Here, we examined relationship between variants voltage-gated sodium channel Na V 1.7...
The α2δ-1 subunit of voltage-gated calcium channels is upregulated after sensory nerve injury and also the therapeutic target gabapentinoid drugs. It therefore likely to play a key role in development neuropathic pain. In this study, we have examined mice which gene expression disrupted, determine whether involved various modalities nociception, for behavioral hypersensitivity partial sciatic ligation (PSNL). We find that naive α2δ-1(-/-) show marked deficit mechanical cold sensitivity, but...
The study of rare families with inherited pain insensitivity can identify new human-validated analgesic drug targets. Here, a 66-yr-old female presented nil requirement for postoperative analgesia after normally painful orthopaedic hand surgery (trapeziectomy). Further investigations revealed lifelong history painless injuries, such as frequent cuts and burns, which were observed to heal quickly. We report the causative mutations this disorder: co-inheritance (i) microdeletion in dorsal root...
Cancer and its treatment exert a heavy psychological physical toll. Of the myriad symptoms which result, pain is common, encountered in between 30% 60% of cancer survivors. Pain survivors major growing problem, impeding recovery rehabilitation patients who have beaten negatively impacting on patients’ quality life, work prospects mental health. Persistent remains challenging to treat successfully. can arise both due underlying disease various treatments patient has been subjected to....
HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of HIV infection and major source morbidity. A cross-sectional deep profiling study examining HIV-SN was conducted in people living with high resource setting using battery measures which included the following: parameters pain symptoms (7day diary, Neuropathic Pain Symptom Inventory [NPSI] Brief [BPI]), innervation (structured neurological examination, quantitative testing [QST] intraepidermal nerve fibre density...
We identified and clinically investigated two patients with primary erythromelalgia mutations (PEM), which are the first reported to map fourth domain of Nav1.7 (DIV). The (A1746G W1538R) were cloned transfected cell cultures followed by electrophysiological analysis in whole-cell configuration. presented PEM, while age onset was very different (3 vs. 61 years age). Electrophysiological characterization revealed that early A1746G mutation leads a marked hyperpolarizing shift voltage...
Abstract Background: Epidemiological studies in patients with neuropathic pain demonstrate a strong association psychiatric conditions such as anxiety; however, the precipitating pathology between these symptoms remains unclear. To investigate this, we studied effects of lifelong stress on levels pain–like behavior and conversely, chronic injury anxiety-like status male female mice. In addition, assayed this link painful painless diabetic peripheral neuropathy patients. Methods: Male mice...
Chronic pain is a major global public health issue causing severe impact on both the quality of life for sufferers and wider economy. Despite significant clinical burden, little progress has been made in terms therapeutic development. A unique approach to identifying new human-validated analgesic drug targets study rare families with inherited insensitivity. Here we have analysed an otherwise normal family where six affected individuals display insensitive phenotype that characterized by...
The spatial resolution of sensory systems is not homogeneous across their receptive surfaces. For example, tactile acuity greatest on the fingertips, reflecting high innervation density and small mechanoreceptive fields in this area [1Sato T. Okada Y. Miyamoto Fujiyama R. Distributions spots hand two-point discrimination thresholds hand, face mouth dental students.J. Physiol. Paris. 1999; 93: 245-250Crossref PubMed Scopus (30) Google Scholar, 2Johnson K.O. Phillips J.R. Tactile resolution....
We identified a patient with severe inherited erythromelalgia secondary to an L858F mutation in the voltage-gated sodium channel Na(v)1.7. The reported ongoing foot pain, which was exquisitely sensitive limb cooling. confirmed this heat hypersensitivity using quantitative sensory testing. Additionally, we employed novel perfusion imaging technique simple block design assess her baseline pain vs cooling relief. Robust activations of key pain-affect, and reward-related centres were observed....
Abstract Aims/hypothesis Distal diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes with many patients showing reduction intraepidermal nerve fibre density (IENFD) from skin biopsy, validated and sensitive diagnostic tool for the assessment DSP. Axonal swelling ratio morphological quantification altered in It is, however, unclear if axonal swellings are related to or The aim this study was investigate how cutaneous fibres type 2 mellitus, DSP neuropathic pain...
We report an English kindred affected across 4 generations with a hereditary neuropathy associated debilitating neuropathic pain as the main clinical feature. The principal finding on examination was sensory loss, and there variable motor dysfunction. Electrophysiological studies revealed mild features of demyelination median conduction velocity in intermediate range. There autosomal-dominant pattern inheritance, genetic testing novel heterozygous Trp101X mutation exon 3 coding for portion...
The term nociception was originally defined by Sherrington1 as the neural process which high-threshold stimuli (which cause tissue injury) are detected. This is distinct from pain, quality of sensory percept (i.e., unpleasant), not always evoked a noxious stimulus, and can also be experienced in absence stimulus. In man, recessive loss function mutations SCN9A gene, encoding α subunit Nav1.7, results anosmia congenital inability to experience pain,2–4 but there have been few reports detailed...
We report a patient from Panama who had lobomycosis caused by Paracoccidioides (Lacazia) loboi. used combined clinical-epidemiologic and phylogenetic data, including new gene sequence dataset on this fungus in Panama, for analysis. Findings contribute useful insights to limited knowledge of fungal infection the Mesoamerican Biologic Corridor.
We report a patient with lobomycosis caused by Paracoccidioides loboi fungi in the Andes-Amazon region of Bolivia. examined clinical, epidemiologic, and phylogenetic data describe potential transmission/environmental aspects infection. Continued surveillance identification cases South America are crucial to prevent spread this disease.
The spatial resolution of sensory systems is not homogeneous across their receptive surfaces. For example, tactile acuity greatest on the fingertips, reflecting high innervation density and small mechanoreceptive fields in this area [1, 2]. In contrast, pain considered to lack any equivalent fovea where nociceptive fibers remarkably low [3]. Here, by combining psychophysics with histology, we show that established notion incorrect. By delivering small-diameter nociceptive-specific laser...