Annina Schmid

University of Oxford | OX · Nuffield Department of Clinical Neurosciences

Focal nerve injuries are often associated with neuropathic pain. Preclinical research suggests altered neuroimmune signalling underlies such neuropathic pain; however, its cause remains poorly understood in humans. In this multicentre cohort study, we describe the local cellular and molecular signature of neuropathic pain at the lesion site, using...

Peripheral neuropathic pain remains challenging to treat, partly due to our limited understanding of the molecular mechanisms at play in humans. In this multicentre cohort study, we describe the local molecular signature of neuropathic pain at the lesion site, using peripheral nerves of patients with Morton's neuroma as a human model system of neur...

Neuropathic pain remains difficult to treat, with drug development hampered by an incomplete understanding of the pathogenesis of the condition, as well as a lack of biomarkers. The problem is compounded by the scarcity of relevant human peripheral tissues, including skin, nerves, and dorsal root ganglia. Efforts to obtain such samples are accelera...

Purpose To establish the prevalence and agreement between reported and observed leg weakness in people with sciatica. To establish which factors mediate any identified difference between reported and observed leg weakness in people with sciatica. Methods 68 people with a clinical diagnosis of sciatica, records from spinal service, secondary care N...

Introduction Neuropathic pain is a highly prevalent condition associated with persistent disability. Some patients with neuropathic pain experience symptom spread outside neuroanatomical boundaries; these patients report more severe sensory symptoms and greater disability. However, the mechanisms behind such symptom spread are not fully understood....

Background The current standard to evaluate the presence of somatosensory dysfunctions is quantitative sensory testing, but its clinical utility remains limited. Low-cost and time-efficient clinical sensory testing (CST) batteries have thus been developed. Recent studies show moderate to substantial reliability in populations with neuropathic pain....

Symptoms in people with carpal tunnel syndrome (CTS) are traditionally attributed to neural tissue, but recent studies suggest that the subsynovial connective tissue (SSCT) may also play a role in CTS. The SSCT undergoes fibrotic thickening which is generally described as “non-inflammatory” based on basic histology. This study uses immunohistochemi...

The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in...

Introduction: Sciatica is a common condition and is associated with higher levels of pain, disability, poorer quality of life, and increased use of health resources compared with low back pain alone. Although many patients recover, a third develop persistent sciatica symptoms. It remains unclear, why some patients develop persistent sciatica as no...

This preclinical systematic review aimed to determine the effectiveness of different types and doses of exercise on pain behaviour and biomarkers in preclinical models of focal neuropathic pain. We searched MEDLINE, EMBASE, Web of Science, PubMed, SCOPUS, CINAHL and Cochrane library from inception to November 2022 for preclinical studies evaluating...

Bei neuromuskuloskelettalen Schmerzen gehören neurodynamische Tests zur physiotherapeutischen Standarduntersuchung. Oftmals aber werden sie falsch interpretiert. Tatsächlich eignen sie sich weder für die Diagnostik einer Nervenläsion noch attestieren sie eine Verkürzung oder verminderte Gleitfähigkeit eines Nervs. Ein Update zum aktuellen Wissensst...

Purpose Physiotherapy interventions are prescribed as first-line treatment for people with sciatica; however, their effectiveness remains controversial. The purpose of this systematic review was to establish the short-, medium- and long-term effectiveness of physiotherapy interventions compared to control interventions for people with clinically di...

Importance Peripheral neuropathies are common conditions and can result in numbness, paresthesia, motor deficits, and pain. There is increasing evidence for the use of biomarkers as clinical indicators of the presence, severity, and prognosis of nerve lesions; however, biomarker identification has largely been focused on disorders of the central ne...

Introduction Whiplash-associated disorder grade 2 (WAD2) is characterised by musculoskeletal pain/tenderness but no apparent nerve injury. However, studies have found clinical features indicative of neuropathy and neuropathic pain. These studies may indicate peripheral nerve inflammation, since preclinical neuritis models found mechanical sensitivi...

Growth-associated protein 43 (GAP-43) has long been used as a marker for nerve regeneration following nerve injury, with numerous in vitro and animal studies showing its upregulation in regenerating neurons. In humans, expression of GAP-43 has predominantly been examined in skin biopsies from patients with peripheral neuropathies; with several stud...

Publications related to pain research have increased significantly in recent years. The abundance of new evidence creates challenges staying up to date with the latest information. A comprehensive understanding of the literature is important for both clinicians and investigators involved in pain research. One commonly used method to combine and ana...

Background Trigger finger and carpal tunnel syndrome are the two most common non-traumatic connective tissue disorders of the hand. Both of these conditions frequently co-occur, often in patients with rheumatoid arthritis. However, this phenotypic association is poorly understood. Hypothesising that the co-occurrence of trigger finger and carpal tu...

Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is “wind-up,” in which dorsal horn spinal neurons increase their response to repeated nociceptor stimulation. To understand the genetic basis...

Introduction : Several phenotypic factors are associated in the literature with an increased risk of carpal tunnel syndrome (CTS). Along with female sex and older age, certain systemic diseases show an association with CTS, with varying degrees of evidence. Methods : This study was performed using the UK Biobank resource – a cohort study of over 5...

There is no clear understanding of the mechanisms causing persistent pain in patients with whiplash-associated disorder (WAD). The aim of this systematic review was to assess the evidence for nerve pathology and neuropathic pain in patients with WAD. EMBASE, PubMed, CINAHL (EBSCO), and MEDLINE were searched from inception to September 1, 2020. Stud...

Trigger finger (TF) and carpal tunnel syndrome (CTS) are two common non-traumatic hand disorders that frequently co-occur. By identifying TF and CTS cases in UK Biobank (UKB), we confirmed a highly significant phenotypic association between the diseases. To investigate the genetic basis for this association we performed a genome-wide association st...

Entrapment neuropathies such as carpal tunnel syndrome, radiculopathies, or radicular pain are the most common peripheral neuropathies and also the most common cause for neuropathic pain. Despite their high prevalence, they often remain challenging to diagnose and manage in a clinical setting. Summarising the evidence from both preclinical and clin...

The role that inflammation plays in human nerve injury and neuropathic pain is incompletely understood. Previous studies highlight the role of inflammation in the generation and maintenance of neuropathic pain, but the emerging evidence from the preclinical literature for its role in the resolution of neuropathic pain remains to be explored in huma...

Background: Therapist-led pathways have been proposed as waitlist management strategies prior to surgery for conditions such as carpal tunnel syndrome (CTS) in public hospitals. These models of care typically shift the initial care of patients and decision-making from surgeons to therapists and, have been shown to reduce the number of patients req...

Despite normal neurological integrity tests, some patients with non-specific neck-arm pain (NSNAP) have heightened nerve mechanosensitivity upon neurodynamic testing. The aim of this study was to determine whether or not a nerve dysfunction is present in patients with positive neurodynamic tests compared to those with negative neurodynamic tests or...

Entrapment neuropathies such as carpal tunnel syndrome, radiculopathies, or radicular pain are the most common peripheral neuropathies and also the most common cause for neuropathic pain. Despite their high prevalence, they often remain challenging to diagnose and manage in a clinical setting. Summarising the evidence from both preclinical and clin...

We only have a rudimentary understanding of the molecular and cellular determinants of nerve regeneration and neuropathic pain in humans. This cohort study uses the most common entrapment neuropathy (carpal tunnel syndrome) as a human model system to prospectively evaluate the cellular and molecular correlates of neural regeneration and its relatio...

Question In people with carpal tunnel syndrome who are waitlisted for surgical consultation, does a therapist-led care pathway involving education, splinting and exercises reduce the need for surgery and improve patient outcomes? Design A multicentre, randomised controlled trial with concealed allocation, blinded assessment and intention-to-treat...

Background: Mechanisms underpinning ongoing symptoms in chronic whiplash associated-disorder (WAD) are not well understood. People with chronic WAD can exhibit sensory dysfunction consistent with small nerve fibre pathology, including thermal hypoaesthesia and hyperalgesia. This study investigated small fibre structure and function in chronic WAD....

Zusammenfassung Wir kennen neurodynamische Tests und Behandlungsmethoden, nutzen diese alltäglich in der Praxis und gehen auf Kurse, um mehr darüber zu lernen. Aber was verstehen wir tatsächlich darunter? Kommen wir in unserem Verständnis darüber auf einen gemeinsamen Nenner? Dieser Artikel gibt einen Einblick in die Thematik Neurodynamik. Bisherig...

Background: This study describes a low-cost and time-efficient clinical sensory test battery (CST), and evaluates its concurrent validity as a screening tool to detect somatosensory dysfunction as determined by quantitative sensory testing (QST). Method: Three patient cohorts with carpal tunnel syndrome (CTS, n=76), non-specific neck and arm pai...

We only have a rudimentary understanding of the molecular and cellular determinants of human nerve regeneration. Here, we use carpal tunnel syndrome (CTS) as a human model system to prospectively evaluate correlates of neural regeneration and their relationship with clinical recovery after decompression surgery. At 6 months post-surgery, we noted a...

Introduction Pain constitutes a major component of the global burden of diseases. Recent studies suggest a strong genetic contribution to pain susceptibility and severity. Whereas most of the available evidence relies on candidate gene association or linkage studies, research on the genetic basis of pain sensitivity using genome-wide association st...

Carpal tunnel syndrome (CTS) is a common and disabling condition of the hand caused by entrapment of the median nerve at the level of the wrist. It is the commonest entrapment neuropathy, with estimates of prevalence ranging between 5–10%. Here, we undertake a genome-wide association study (GWAS) of an entrapment neuropathy, using 12,312 CTS cases...

Purpose: Intervertebral disk (IVD) lesion and its subsequent degeneration have a profound effect on the multifidus muscle. The subacute/early chronic phase of multifidus remodeling after IVD lesion has been proposed to be regulated by inflammatory processes. The balance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages plays an...

Objectives: The aim of this study was to describe the development of morphologic and diffusion tensor imaging sequences of peripheral nerves at 7 T, using carpal tunnel syndrome (CTS) as a model system of focal nerve injury. Materials and methods: Morphologic images were acquired at 7 T using a balanced steady-state free precession sequence. Dif...

Objective: Distal and proximal entrapment neuropathies such as carpal tunnel syndrome (CTS) and cervical radiculopathy (CR) share similar etiologies. Experimental models suggest that despite comparable etiology, pathomechanisms associated with injuries of the peripheral and central axon branches are distinct. This study therefore compared self-rep...

Entrapment neuropathies are the most prevalent type of peripheral neuropathy and often a challenge to diagnose and treat. To a large extent, our current knowledge is based on empirical concepts and early (often biomechanical) studies. This Viewpoint will challenge some of the current beliefs with recent advances in both basic and clinical neuroscie...

Preliminary evidence from studies using quantitative sensory testing suggests the presence of central mechanisms in patients with carpal tunnel syndrome (CTS) as apparent by widespread hyperalgesia. Hallmarks of central mechanisms after nerve injuries include nociceptive facilitation and reduced endogenous pain inhibition. Methods to study nocicept...

Introduction: Carpal tunnel syndrome (CTS) is a prevalent upper limb condition that results in significant individual and socioeconomic costs. Large patient numbers, long outpatient waiting times and traditional referral pathways in public health systems create delays in accessing treatment for this condition. Alternative care pathways aimed at st...

Objective: To examine differences in somatosensory phenotypes of patients with positive and negative neurodynamic tests and compare these with healthy participants. Design: Case-control study. Setting: University department. Participants: Patients with electrodiagnostically confirmed carpal tunnel syndrome (CTS) (n=53) and people without CTS...

Introduction The multifidus muscle undergoes structural and behavioral changes with back pain and injury. After intervertebral disc (IVD) lesion in animals the multifidus muscle undergoes a transformation of muscle fiber types from slow-to-fast, and extensive structural remodelling with increased adipose and connective tissue. Increased expression...

Study design: Longitudinal case control animal model. Objective: To investigate effects of mesenchymal stem cell (MSC) treatment on multifidus muscle remodeling after intervertebral disc (IVD) lesion. Summary of background data: Lesion and degeneration of IVDs causes structural remodeling of the multifidus muscle. Pro-inflammatory cytokines ar...

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Neuropathic pain following peripheral nerve injury is associated with hyperexcitability in damaged myelinated sensory axons, which begins to normalise over time. We investigated the composition and distribution of shaker-type-potassium channels (Kv1 channels) within the nodal complex of myelinated axons following injury. At the neuroma that forms a...

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of indivi...