Irene Tracey's research while affiliated with Oxford University Hospitals NHS Trust and other places

Publications (269)

Article
Full-text available
Background IMI2-PainCare-BioPain-RCT2 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on specific compartments of the nociceptive system that could serve to accelerate the future development of analgesics. IMI2-PainCare-BioPain-RCT2 will focus on human spinal cord and brainstem a...
Article
Full-text available
There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials despite promising preclinical results. Translational assessment tools to verify engagement of pharmacological targets a...
Article
Full-text available
Chronic pain in multiple sclerosis is common, and difficult to treat. Its mechanisms remain incompletely understood. Dysfunction of the descending pain modulatory system is known to contribute to human chronic pain conditions. However, it is not clear how alterations in executive function influence this network, despite healthy volunteer studies li...
Preprint
Objectives Chronic pelvic pain is common, poorly understood, and many women suffer for years without proper diagnosis and effective treatment. The Translational Research in Pelvic Pain (TRiPP) project takes a phenotyping approach, with a particular focus on endometriosis-associated pain (EAP) and bladder pain syndrome (IC/BPS), to improve our funda...
Article
The neural mechanisms underlying placebo analgesia have attracted considerable attention over the recent years. In contrast, little is known about the neural underpinnings of a nocebo‐induced increase in pain. We previously showed that nocebo‐induced hyperalgesia is accompanied by increased activity in the hippocampus that scaled with the perceived...
Article
Background/Aims Sleep problems are common in fibromyalgia (FM) and chronic widespread pain (CWP), and may result in similar structural brain changes as those seen in chronic pain. However, the exact neural mechanisms are not fully understood. Studies to date are relatively small and yield conflicting results. The aim of this study is to investigate...
Article
Full-text available
The claustrum is the most densely interconnected region in the human brain. Despite the accumulating data from clinical and experimental studies, the functional role of the claustrum remains unknown. Here, we systematically review claustrum lesion studies and discuss their functional implications. Claustral lesions are associated with an array of s...
Article
Full-text available
Background Few new drugs have been developed for chronic pain. Drug development is challenged by uncertainty about whether the drug engages the human target sufficiently to have a meaningful pharmacodynamic effect. IMI2-PainCare-BioPain-RCT1 is one of four similarly designed studies that aim to link different functional biomarkers of drug effects o...
Article
Neuroimaging methods can be used to identify biomarkers of acute and chronic pain.
Article
Prior expectations can bias how we perceive pain. Using a drift diffusion model, we recently showed that this influence is primarily based on changes in perceptual decision-making (indexed as shift in starting point). Only during unexpected application of high-intensity noxious stimuli, altered information processing (indexed as increase in drift r...
Article
Full-text available
Background The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. Objectives To provide a summary of knowledge on placebo control...
Article
Full-text available
Nociceptive processing in the human brain is complex and involves several brain structures and varies across individuals. Determining the structures that contribute to interindividual differences in nociceptive processing is likely to improve our understanding of why some individuals feel more pain than others. Here, we found specific parts of the...
Preprint
Full-text available
Cortical remapping after hand loss in the primary somatosensory cortex (S1) is thought to be predominantly dictated by cortical proximity, with adjacent body parts remapping into the deprived area. Traditionally, this remapping has been characterised by changes in the lip representation, which is assumed to be the immediate neighbour of the hand ba...
Preprint
The claustrum is the most densely interconnected region in the human brain. Despite the accumulating data from clinical and experimental studies, the functional role(s) of the claustrum remain unknown. Here, we systematically review claustrum lesion studies and discuss their functional implications. Claustral lesions are associated with an array of...
Article
Full-text available
Background IMI2-PainCare-BioPain-RCT3 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics, by providing a quantitative understanding between drug exposure and effects of the drug on nocicept...
Article
Full-text available
Magnetic Resonance Spectroscopy (MRS) allows for the non-invasive quantification of neurochemicals and has the potential to differentiate between the pathologically distinct diseases, multiple sclerosis (MS) and AQP4Ab-positive neuromyelitis optica spectrum disorder (AQP4Ab-NMOSD). In this study we characterised the metabolite profiles of brain les...
Article
Background/Aims Population-based studies suggest an association between pain in elderly adults and cognitive impairment. However, the temporal relationship between chronic pain and cognitive decline is uncertain: most studies are cross-sectional or have short follow-up periods. Our aim was to examine the association between two pain phenotypes - b...
Preprint
Arterial spin labelling (ASL) FMRI is a powerful tool to non-invasively image tonic and ongoing pain states in both healthy participants and patients. We used ASL to image the neural correlates of extended, parametrically modulated mechanical pain in healthy human participants. The aims of this study were to: i) assess if force-calibrated pin-prick...
Article
Full-text available
Background As in other fields of medicine, development of new medications for management of neuropathic pain has been difficult since preclinical rodent models do not necessarily translate to the clinics. Aside from ongoing pain with burning or shock‐like qualities, neuropathic pain is often characterized by pain hypersensitivity (hyperalgesia and...
Article
Full-text available
The brain systems underlying placebo analgesia are insufficiently understood. Here we performed a systematic, participant-level meta-analysis of experimental functional neuroimaging studies of evoked pain under stimulus-intensity-matched placebo and control conditions, encompassing 603 healthy participants from 20 (out of 28 eligible) studies. We f...
Article
Full-text available
Key points: We use massive irreparable rotator cuff tear as a model to study the impact of chronic pain and motor impairment on the motor systems of the human brain using Magnetic Resonance Imaging (MRI). Patients show markers of lower grey/white matter integrity and lower functional connectivity compared with control participants in regions respo...
Preprint
Full-text available
Nociceptive processing in the human brain is a signal that enables harm avoidance, with large interindividual variance. The relative contributions of genes and environment to the neural structures that support nociception have not been studied in twins previously. Here, we employed a classic twin-design to determine brain structures influenced by a...
Article
Full-text available
Background: Chronic pelvic pain affects 2–24% of women worldwide and evidence for medical treatments is scarce. Gabapentin is effective in treating some chronic pain conditions. We aimed to measure the efficacy and safety of gabapentin in women with chronic pelvic pain and no obvious pelvic pathology. Methods: We performed a multicentre, randomised...
Article
Full-text available
We investigated how the attenuation of pain with cognitive interventions affects brain connectivity using neuroimaging and a whole brain novel analysis approach. While receiving tonic cold pain, 20 healthy participants performed three different pain attenuation strategies during simultaneous collection of functional imaging data at seven tesla. Par...
Article
Full-text available
We investigated how the attenuation of pain with cognitive interventions affects brain connectivity using neuroimaging and a whole brain novel analysis approach. While receiving tonic cold pain, 20 healthy participants performed three different pain attenuation strategies during simultaneous collection of functional imaging data at 7 tesla. Partici...
Article
Full-text available
We investigated how the attenuation of pain with cognitive interventions affects brain connectivity using neuroimaging and a whole brain novel analysis approach. While receiving tonic cold pain, 20 healthy participants performed three different pain attenuation strategies during simultaneous collection of functional imaging data at seven tesla. Par...
Preprint
Full-text available
Magnetic Resonance Spectroscopy (MRS) allows for the non-invasive quantification of neurochemicals and has the potential to differentiate between the pathologically distinct diseases, multiple sclerosis (MS) and AQP4Ab-positive neuromyelitis optica spectrum disorder (AQP4Ab-NMOSD). In this study we characterised the metabolite profiles of brain les...
Article
Full-text available
Pain medication plays an important role in the treatment of acute and chronic pain conditions, but some drugs, opioids in particular, have been overprescribed or prescribed without adequate safeguards, leading to an alarming rise in medication-related overdose deaths. The NIH Helping to End Addiction Long-term (HEAL) Initiative is a trans-agency ef...
Article
Background Rheumatoid arthritis (RA) is a common, painful and disabling condition. Despite effective treatment of inflammation, many patients continue to experience ongoing pain. Central sensitisation could explain this apparent discordance, but at current is not routinely assessed in clinical practice. Previous studies have used the non-inflammato...
Article
The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were i...
Article
Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challe...
Chapter
Chronic pain is a medical health problem affecting almost 20% of the population in Europe, with an important impact on patients’ function, quality of life, social interactions, and mental health. This chapter reviews the current understanding of the processes and neural mechanisms involved in nociception and the regulation of pain perception. Facto...
Article
Objectives: Fibromyalgia is a complex, debilitating, multifactorial condition that can be difficult to manage. Recommended treatments are usually delivered in outpatient settings; evidence suggests that significant inpatient care occurs. We describe the scale and cost of inpatient care with a primary diagnostic code of fibromyalgia within the Engl...
Article
Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this paper is to provide a summary of current knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group and, although powerful, presents many challenges in a surgica...
Preprint
The perception of pain activates a number of brain regions and processes that are involved in its sensory, emotional, cognitive, and affective aspects; all of which require a flexible functional connectivity between local and distant brain regions. Here, we investigate how the attenuation of pain with cognitive interventions affects the strength of...
Article
Full-text available
Purpose: To assess the impact of the different post-processing options in the calibration of arterial spin labeling (ASL) data on perfusion quantification and its reproducibility. Theory and methods: Absolute quantification of perfusion measurements is one of the promises of ASL techniques. However, it is highly dependent on a calibration proced...
Article
Full-text available
Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory relate...
Article
Arterial Spin Labeling (ASL) is a perfusion-based functional magnetic resonance imaging technique that uses water in arterial blood as a freely diffusible tracer to measure regional cerebral blood flow (rCBF) noninvasively. To date its application to the study of pain has been relatively limited. Yet, ASL possesses key features that make it uniquel...
Preprint
The spatial representation of nociceptive input in the human parietal cortex is not fully understood. For instance, it is known that the primary somatosensory cortex (S1) contains a representation of nociceptive-selective input to different fingers, but it is unclear whether S1 subdivisions contain finer-grained, within-finger maps of nociceptive i...
Article
Pain is a subjective sensory experience that can, mostly, be reported but cannot be directly measured or quantified. Nevertheless, a suite of biomarkers related to mechanisms, neural activity, and susceptibility offer the possibility—especially when used in combination—to produce objective pain-related indicators with the specificity and sensitivit...
Article
Full-text available
Purpose Spinal cord MRI at ultrahigh field is hampered by time‐varying magnetic fields associated with the breathing cycle, giving rise to ghosting artifacts in multi‐shot acquisitions. Here, we suggest a correction approach based on linking the signal from a respiratory bellows to field changes inside the spinal cord. The information is used to co...
Article
Full-text available
Loss-of-function mutations in NaV1.7 cause congenital insensitivity to pain (CIP); this voltage-gated sodium channel is therefore a key target for analgesic drug development. Utilizing a multi-modal approach, we investigated how NaV1.7 mutations lead to human pain insensitivity. Skin biopsy and microneurography revealed an absence of C-fiber nocice...
Article
Thank you very much for the opportunity to reply to the letter from Havsik et al. We are grateful to them for sharing their opinions on the PainDETECT questionnaire and welcome the opportunity to further highlight the advantages and disadvantages of the different tools available for investigating pain characteristics and mechanisms in patients with...
Article
Diabetic distal symmetrical peripheral polyneuropathy (DSP) results in decreased somatosensory cortical gray matter volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has examined whether changes in brain volume alter the functional organization of the somatosensory corte...
Article
Full-text available
Objective Phantom limb pain (PLP) is notoriously difficult to treat, partly due to an incomplete understanding of PLP‐related disease mechanisms. Non‐invasive brain stimulation (NIBS) is used to modulate plasticity in various neuropathological diseases, including chronic pain. While NIBS can alleviate neuropathic pain (including PLP), both disease...
Preprint
Full-text available
Perceptual decision-making is commonly studied using stimuli with different physical properties but of comparable affective value. Here, we investigate neural processes underlying human perceptual decisions in the affectively rich domain of pain using a drift-diffusion model in combination with a probabilistic cueing paradigm. This allowed us to ch...
Article
Full-text available
Objectives The neural mechanisms of pain in knee OA are not fully understood: some patients have neuropathic‐like pain, associated with central sensitisation. We aimed to identify central sensitisation using neuroimaging and PainDETECT, and relate it to post‐arthroplasty outcome. Methods Patients awaiting arthroplasty underwent quantitative sensor...
Article
Full-text available
Objective: To evaluate the impact of the QuinteT Recruitment Intervention (QRI) on recruitment in challenging randomized controlled trials (RCTs) that have applied the intervention. The QRI aims to understand recruitment difficulties and then implements "QRI actions" to address these as recruitment proceeds. Study design and setting: A mixed-met...
Data
Individual DPMS brainstem masks in functional space.
Article
Full-text available
The descending pain modulatory system (DPMS) constitutes a network of widely distributed brain regions whose integrated function is essential for effective modulation of sensory input to the central nervous system and behavioural responses to pain. Animal studies demonstrate that young rodents have an immature DPMS, but comparable studies have not...
Article
Pain is regulated endogenously through both opioid and non-opioid mechanisms. We hypothesized that two novel pain modulation tasks, one drawing on context/expectations and one using voluntary reappraisal, would show differing levels of opioid-dependence. Specifically, we expected that naloxone would block context-related analgesia, whereas mental i...
Preprint
Full-text available
Purpose: Spinal cord MRI at ultra-high field is hampered by time-varying magnetic fields associated with the breathing cycle, giving rise to ghosting artifacts in multi-shot acquisitions. Here, we suggest a correction approach based on linking the signal from a respiratory bellows to field changes inside the spinal cord. The information is used to...
Article
The prevalence of diabetes mellitus and its chronic complications continue to increase alarmingly. Consequently, the massive expenditure on diabetic distal symmetrical polyneuropathy (DSPN) and its sequelae, will also likely rise. Up to 50% of patients with diabetes develop DSPN, and about 20% develop neuropathic pain (painful-DSPN). Painful-DSPN c...
Article
Full-text available
Background: Pregnancy-induced analgesia is known to occur in association with the very high levels of estradiol and progesterone circulating during pregnancy. In women with natural ovulatory menstrual cycles, more modest rises in these hormones occur on a monthly basis. We therefore hypothesized that the high estradiol high progesterone state indic...