Thomas Graven-Nielsen's research while affiliated with Aalborg University and other places

Publications (454)

Article
Multifocal transcranial direct current stimulation (tDCS) targeting several brain regions is promising for inducing cortical plasticity. It remains unknown whether multifocal tDCS aimed at the resting-state motor network (network-tDCS) can revert N2-P2 cortical responses otherwise attenuated during prolonged experimental pain. Thirty-eight healthy...
Article
Background: A subset of osteoarthritis patients will experience chronic postoperative pain after total knee arthroplasty (TKA), but the source of pain is unclear. The aim of this exploratory study was to assess patients with and without postoperative pain after TKA using magnetic resonance imaging (MRI), quantitative sensory testing (QST), clinica...
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Objective We explored differences in postural stability between subgroups of patients with low back pain (LBP) and varying risk levels for developing chronicity measured using the Subgroups for Targeted Treatment (STarT) Back Tool. Methods This was a cross-sectional, single-session, double-blind experimental study among 65 participants who had LBP...
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Purpose of review: Chronic pain is the most prevalent symptomatic disease worldwide. Nonpharmacological interventions, such as noninvasive neuromodulation (NIN), have gained scientific evidence to support their use as an add-on strategy to pharmacological pain management. The most studied NIN technique is repetitive transcranial magnetic stimulati...
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Predicting the development of chronic low back pain (LBP) at the time of an acute episode remains challenging. The Understanding persistent Pain Where it ResiDes (UPWaRD) study aimed to identify neurobiological and psychological risk factors for chronic LBP. Individuals with acute LBP (N=120) participated in a prospective cohort study with six-mont...
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Neck pain is a common musculoskeletal problem often accompanied by reduced exercise-induced hypoalgesia (EIH) or hyperalgesia compared to an asymptomatic population. This study investigated EIH in a healthy population during experimental neck pain. Forty participants were randomized into this double-blinded parallel-group study. On four separate te...
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Objective: To explore the associations between habitual self-reported physical activity, pain sensitivity and patient-reported outcomes (including pain intensity) in patients with chronic pain. Design: Cross-sectional, experimental study. Subjects: Patients (n = 78), age range 18-65 years, with different chronic pain conditions (> 3 months) were c...
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Objectives The posterior-superior insula (PSI) has been shown to be a safe and potentially effective target for neuromodulation in peripheral neuropathic pain (PNP) in humans and animal models. However, it remains unknown whether there is a measurable responder profile to PSI stimulation. Two factors were hypothesized to influence the response of r...
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High definition transcranial direct current stimulation (HD-tDCS) targeting brain areas involved in pain processing has shown analgesic effects in some chronic pain conditions, but less modulatory effect on mechanical and thermal pain thresholds in asymptomatic subjects. This double-blinded study assessed the HD-tDCS effects on experimental pain an...
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Classification of musculoskeletal pain based on underlying pain mechanisms (nociceptive, neuropathic, and nociplastic pain) is challenging. In the absence of a gold standard, verification of features that could aid in discrimination between these mechanisms in clinical practice and research depends on expert consensus. This Delphi expert consensus...
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The angular gyrus (AG) is a common hub in the pain networks. The role of the AG during pain perception, however, is still unclear. This crossover study examined the effect of tonic pain on resting state functional connectivity (rsFC) of the AG under eyes closed (EC) and eyes open (EO). It included two sessions (placebo/pain) separated by 24 hours....
Preprint
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Background Despite chronic low back pain (LBP) being considered a biopsychosocial condition for diagnosis and management, few studies have investigated neurophysiological or neurobiological risk factors thought to underpin the transition from acute to chronic LBP. The aim of this cohort profile is to describe the methodology, compare baseline chara...
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Pathophysiological causes of low back pain (LBP) remain generally unclear, so focus has shifted to psychosocial features and central pain processing. Effects of attentional and affective manipulation on conditioned pain modulation (CPM) and tonic pain perception were examined in thirty recurrent LBP patients in two sessions, one with and one withou...
Preprint
Full-text available
Predicting the development of chronic low back pain (LBP) at the time of an acute episode remains challenging. The Understanding persistent Pain Where it ResiDes (UPWaRD) study aimed to identify neurobiological and psychological risk factors for chronic LBP. Individuals with acute LBP (N=120) participated in a prospective cohort study with six-mont...
Article
Homeostatic plasticity complements synaptic plasticity by stabilising neural activity within a physiological range. In humans, homeostatic plasticity is investigated using two blocks of non-invasive brain stimulation (NIBS) with an interval without stimulation between blocks. The aim of this systematic review and meta-analysis was to investigate th...
Article
Peak alpha frequency (PAF) reduces during cutaneous pain, but no studies have investigated PAF during movement-related muscle pain. Whether high-pain sensitive (HPS) individuals exhibit a more pronounced PAF response to pain than low-pain sensitive (LPS) individuals is unclear. As a pain model, twenty-four participants received nerve growth factor...
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Introduction: Multi-site pain has not been investigated among adolescents suffering from knee pain. This study aimed to examine the trajectory of pain in adolescents with knee-pain, to determine if multi-site pain in adolescents together with other established prognostic factors (frequency of pain, sex, sports participation, Health Related Quality...
Article
Muscle pain can be associated with altered central pain processing, leading to hyperalgesia both locally and at distant body sites. The role of endogenous inhibitory mechanisms in hyperalgesia associated with muscle pain remains unclear. This study investigated the influence of conditioned pain modulation (CPM) on hyperalgesia at multiple body site...
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Background Endogenous pain inhibitory mechanisms are known to reduce pain intensity, but whether they influence the size and distribution of pain referral is unclear. This study aimed to determine if referred pain is reduced by applying a remote, conditioning painful stimulus. Methods Twenty‐four healthy men participated in this randomized, crosso...
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Aberrant synaptic plasticity is hypothesised to underpin chronic pain. Yet, synaptic plasticity regulated by homeostatic mechanisms have received limited attention in pain. We investigated homeostatic plasticity in the human primary motor cortex (M1) of 21 healthy individuals in response to experimentally induced muscle pain for several days. Exper...
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Chronic low back pain (CLBP) is highly disabling, but often without identifiable source. Focus has been on impaired anti-nociceptive mechanisms contributing to pain maintenance, though methods of targeting this impairment remain limited. This randomised-controlled cross-over pilot trial used active versus sham medial prefrontal cortex (mPFC) high-d...
Article
Abstract Objective: Altered balance in nociception in response to noxious stimuli is commonly reported in chronic low back pain (LBP). However, it is unclear whether an improvement in the clinical presentation is contingent on a reduction in pain sensitivity. This study investigated whether the quantitative sensory testing (QST) profile changes in...
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Chronic low back pain (CLBP) is often without clear underlying pathology. Affective disturbance and dysfunctional pain mechanisms, commonly observed in populations with CLBP, have, therefore, been suggested as potential contributors to CLBP development and maintenance. However, little consensus exists on how these features interact and if they can...
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Background: Antinociceptive effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) have been extensively studied in the past years. However, M1 does not work in isolation, but it rather interacts within a network, the so-called resting-state motor network. Objective: To explore the anti-nociceptive effects o...
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Acute pain elicits a well-known inhibitory effect on upper limb corticomotor excitability, whereas the temporal effects of lower-limb experimental pain and pain in a remote limb are less clear. The aim of this study was to compare the temporal corticomotor excitability changes in the upper and lower limbs in response to acute upper and lower limb p...
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For decades, basic research on the underlying mechanisms of nociception has held promise to translate into efficacious treatments for patients with pain. Despite great improvement in the understanding of pain physiology and pathophysiology, translation to novel, effective treatments for acute and chronic pain has however been limited, and they rema...
Article
High-definition transcranial direct current stimulation (HD-tDCS) of brain areas related to pain processing may provide analgesic effects evident in the sensory detection and pain thresholds. The somatosensory sensitivity was assessed following HD-tDCS targeting the primary motor cortex (M1) and/or the dorsolateral prefrontal cortex (DLPFC). Eighty...
Article
Objectives Exercise therapy is recommended for low back pain (LBP) although the immediate effects on pain are highly variable. In 96 individuals with LBP this cross‐sectional study explored 1) the magnitude of exercise‐induced hypoalgesia (EIH), and 2) measures of pain sensitivity and clinical pain manifestations in individuals reporting a clinical...
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Objective: Nociception caused by injuries may sensitize central mechanisms causing expanded pain areas. After recovery, the status of such pain distribution and sensitivity mechanisms is unknown. The present study investigated whether individuals who have fully recovered from a distal radius fracture demonstrate increased pain sensitivity and expa...
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Objective: Nerve growth factor (NGF) is essential for generating and potentiating pain responses. This double-blinded crossover study assessed NGF-evoked pain in healthy humans after repeated NGF injections in the tibialis anterior (TA) muscle compared with control injections of isotonic saline. Subjects: Twenty healthy subjects participated in...
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Purpose: Some individuals with chronic pain find daily life sensations (eg, noise, light, or touch) aversive. This amplification of multisensory sensations has been associated with centrally mediated plasticity; for example, greater multisensory sensitivity (MSS) occurs in patients with fibromyalgia than rheumatoid arthritis. However, whether MSS...
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Objectives: Patients with low back pain (LBP) often demonstrate pain sensitization, high degree of pain catastrophizing, and psychological distress. This study investigated if pain sensitization mechanisms, the pain catastrophizing scale (PCS), and Start Back Screening Tool (SBST) were associated with pain in recurrent LBP patients 12-weeks after...
Article
Phantom limb pain (PLP) may be relieved using a visual representation of an intact limb. However, patients with distorted (telescoped) phantoms seem unable to associate with visualizations of intact limbs. A virtual arm visualization was matched to the individual's phantom perception and controlled in an augmented reality (AR) intervention. Seven P...
Article
Nociceptive withdrawal reflex (NWR) is a protective reaction to a noxious stimulus, resulting in withdrawal of the affected area and thus preventing potential tissue damage. This involuntary reaction consists of neural circuits, biomechanical strategies and muscle activity that ensure an optimal withdrawal. Studies of lower limb NWR indicate that t...
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Background Osgood-Schlatter disease (OSD) affects 1 in 10 adolescents. There is a lack of evidence-based interventions, and passive approaches (eg, rest and avoidance of painful activities) are often prescribed. Purpose To investigate an intervention consisting of education on activity modification and knee-strengthening exercises designed for ado...
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Background Diffuse noxious inhibitory controls (DNIC) as measured in rat and conditioned pain modulation (CPM), the supposed psychophysical paradigm of DNIC measured in humans, are unique manifestations of an endogenous descending modulatory pathway that is activated by application of a noxious conditioning stimulus. The predictive value of the hum...
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Background: Hypogonadism is prevalent during opioid treatment, but the effect of testosterone replacement treatment (TRT) on body composition, pain perception, and adrenal function is unclear. Purpose: To measure changes in body composition, pain perception, quality of life and adrenal function after TRT or placebo in opioid treated men with chroni...
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Chronic musculoskeletal pain is a common problem globally. Current evidence suggests that maladapted central pain pathways are associated with pain chronicity following e.g. post-operative pain after knee replacement. Other factors such as low mood, anxiety and tendency to catastrophize are also important contributors. We aimed to investigate brain...
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Patellofemoral pain (PFP) is a common complaint among young sports active adolescents. This study evaluated the longitudinal changes in pro-nociceptive and anti-nociceptive mechanisms in young adolescents with PFP, their impact on prognosis and responsiveness to treatment. Adolescents (N=151, aged 10-14 years) diagnosed with PFP were compared to ag...
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Study design: Cross-sectional study. Background: Patellofemoral pain (PFP) and Osgood-Schlatter disease (OSD) are common in adolescents, but we lack knowledge on these conditions and their impact in young adolescents (<15 years). Objectives: Compare pain, physical activity, quality of life, strength and knee function between adolescents with P...
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Background: This study investigated 1) if a prolonged noxious stimulus (24-hr topical capsaicin) in healthy adults would impair central pain inhibitory and facilitatory systems measured as a reduction in conditioned pain modulation (CPM) and enhancement of temporal summation of pain (TSP) and 2) if acute pain relief or exacerbation (cooling and he...
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Altered pro-nociceptive and anti-nociceptive mechanisms are often implicated in painful conditions and have been increasingly studied over the past decade. For some painful conditions alterations are well-established, but in low back pain (LBP) populations there remains considerable debate whether these mechanisms are altered. The present systemati...
Preprint
Chronic musculoskeletal pain is a common problem globally. Current evidence suggests that maladaptive modulation of central pain pathways is associated with pain chronicity following e.g. chronic post-operative pain after knee replacement. Other factors such as low mood, anxiety and tendency to catastrophize seem to also be important contributors....
Article
Background: Impaired sensorimotor ability has been demonstrated in recurrent neck pain patients. It is however not clear if cervical joint motion and pressure pain sensitivity in recurrent neck pain patients are different from asymptomatic controls. Methods: Cervical flexion and extension motions were examined by video-fluoroscopy and pressure p...
Article
Objectives: The aim of this study was to compare the acute effects of isometric versus dynamic resistance exercise on pain during a pain-provoking activity, and exercise-induced hypoalgesia in participants with patellar tendinopathy. Design: This study was a pre-registered randomised crossover study. Participants were blinded to the study hypoth...
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Background and aims Neck pain can impair perception of cervical movement, but how this is affected by attention is unknown. In this study, the effects of experimental neck pain on head repositioning accuracy during standardized head movements were investigated. Methods Experimental neck pain was induced by injecting hypertonic saline into the righ...
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Purpose To quantify how postural stability is modified during experimental pain while performing different cognitively demanding tasks. Methods Sixteen healthy young adults participated in the experiment. Pain was induced by intramuscular injection of hypertonic saline solution (1 mL, 6%) in both vastus medialis and vastus lateralis muscles (0.9%...
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Experimental pain inhibits primary motor cortex (M1) excitability. Attenuating pain-related inhibition of M1 excitability may be useful during rehabilitation in individuals with pain. One strategy to attenuate M1 excitability is to influence prefrontal and premotor cortex activity. Working memory tasks, e.g. the two-back task (TBT), engage prefront...
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Background: Patellofemoral pain (PFP) is a common knee pain condition where hip and knee exercises help improve treatment outcomes. This study compared the acute effect of hip versus knee exercises on anti-nociceptive and pro-nociceptive mechanisms in young females with long-standing PFP. Methods: In this randomized cross-over study, 29 females...
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Low back pain (LBP) has been inconsistently associated with enhanced pro-nociceptive and impaired anti-nociceptive mechanisms. It remains unknown whether alterations are causal, consequential or coincidental to pain presence. This study investigated pro-nociceptive and anti-nociceptive mechanisms in recurrent LBP (RLBP) patients across painful and...
Article
Background: Intramuscular injection of Nerve Growth Factor (NGF) may influence the responsiveness of active chemo-sensitive channels affecting muscle pain sensitivity. This double-blinded crossover study in healthy humans assessed contraction-evoked pain responses and pain sensitivity during acute ischemia in the tibialis anterior (TA) muscle befo...
Preprint
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Unaccustomed eccentric exercise leads to impaired microvascular function but the underlying mechanism is unknown. In this study, we evaluated the role of oxidative stress and of nitric oxide (NO) bioavailability. Thirty young men and women performed eccentric contractions of the tibialis anterior (TA) muscle (ECC), with the contralateral leg servin...
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Background: Efficacy of pain modulation is assessed as the difference in pain sensitivity during a painful conditioning, compared to before (conditioning pain modulation, CPM). Attention can be assessed with the Stroop-task, in which participants report the number of words on a screen; either congruent or incongruent with the value of the words. A...
Article
Background: Patellofemoral pain (PFP) affects 7% of adolescents, especially those who are highly active. Exercise-focused treatments show limited effect and overlook activity modification and load management. As many adolescents continue at high levels of sports despite pain, a new strategy addressing this problem is warranted. Purpose: To inves...
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Introduction Low back pain (LBP) is the leading cause of disability worldwide, with prevalence doubling in the past 14 years. To date, prognostic screening tools display poor discrimination and offer no net benefit of screening over and above a ‘treat all’ approach. Characteristics of the primary sensory (S1) and motor (M1) cortices may predict the...
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Musculoskeletal pain is associated with altered motor control that despite short-term benefit, is hypothesised to have long-term consequences, contributing to the development of chronic pain. However, data on how motor control is altered when pain is sustained beyond a transient event are scarce. Here, we investigated motor adaptation, and its rela...
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Purpose: The remodeling of functional neuronal connectivity in chronic widespread pain (CWP) patients remains largely unexplored. This study aimed to investigate functional connectivity in CWP patients in brain networks related to chronic pain for changes related to pain sensitivity, psychological strain, and experienced pain. Patients and methods:...
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The 10 Hz repetitive transcranial magnetic stimulation (10 Hz-rTMS) to the left dorsolateral prefrontal cortex produces analgesia, probably by activating the pain modulation system. A newer rTMS paradigm, called theta burst stimulation (TBS), has been developed. Unlike 10 Hz-rTMS, prolonged continuous TBS (pcTBS) mimics endogenous theta rhythms, wh...
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Musculoskeletal pain reduces corticomotor excitability (CE) and methods modulating such CE reduction remain elusive. This study aimed to modulate pain-induced CE reduction by performing action observation and motor imagery (AOMI) during experimental muscle pain. Twelve healthy subjects participated in three cross-over and randomized sessions separa...
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Background Pro‐nociceptive and anti‐nociceptive mechanisms are commonly assessed in clinical and experimental pain studies, while their potential interaction is not well understood. Objectives Investigate the effect of conditioning pain modulation (CPM) on temporal summation of pain (TSP). Methods Twenty healthy participants underwent cuff algome...
Article
Background: Although the cervical interspinous ligament is a potential source of neck pain, the effects on cervical joint motion and pressure pain sensitivity has never been investigated. The understanding of the relationship will broaden our understanding of cervical biomechanics and improve diagnosis and treatment of neck pain. Methods: Fluoro...
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Introduction:. Joint position sense (JPS) is impaired in clinical musculoskeletal pain conditions, but when this impairment develops in the transition from initial to prolonged pain is not known. Objectives:. This study assessed whether progressively developing sustained experimentally induced muscle pain impacts JPS in healthy individuals. Methods...
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Purpose of review: The purpose of this review is to summarize recent findings on conditioned pain modulation (CPM) in humans with a focus on methodology, factors modulating CPM, and the potential for CPM as a clinical marker for pain progression. Recent findings: CPM can be evoked by combining different stimulus modalities with good reliability;...
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Exercise is considered an important component of effective chronic pain management and it is well-established that long-term exercise training provides pain relief. In healthy, pain-free populations, a single bout of aerobic or resistance exercise typically leads to exercise-induced hypoalgesia (EIH), a generalized reduction in pain and pain sensit...
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Purpose Exercise decreases pain sensitivity known as exercise-induced hypoalgesia (EIH). However, the consistency of EIH after an acute exercise protocol based on subjective ratings of perceived exertion has been questioned. Objectives were to compare the effect on pressure pain thresholds (PPTs) after bicycling with work-rate at the lactate thresh...
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Background: Antidepressants may increase the risk of fractures through negative effects on the musculoskeletal system that could be hindered by vitamin D supplements. Objectives: To study the pleiotropic effects of daily vitamin D supplementation in depressed patients treated with citalopram (patients) and healthy controls. Design: Randomised doubl...
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Intramuscular injection of nerve growth factor (NGF) causes muscle hyperalgesia without immediate pain. This double-blinded, randomized study assessed pain and muscle hypersensitivity after a single-site bolus NGF injection (5 µg) compared with 5 spatially distributed, low-dose NGF injections (1 µg, 4 cm distance) into the tibialis anterior (TA) mu...