ORCID Profile
0000-0002-4993-5101
Current Organisation
University of Queensland
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 02-08-2018
DOI: 10.1002/FEE.1934
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.JPAIN.2019.03.001
Abstract: Central sensitization is considered to have a pathophysiological role in chronic low back pain (LBP). Whether in iduals with increased central sensitization early in their condition are more likely to develop persistent pain or whether it increases over time is unclear. This study aimed to determine whether sensory profiles during acute LBP differ between in iduals who did and did not recover by 6 months and to identify subgroups associated with outcomes. In iduals with acute LBP (<2 weeks of onset N = 99) underwent pain threshold (heat/cold ressure) and conditioned pain modulation testing after completing questionnaires related to pain/disability, sleep, and psychological status. Sensory measures were compared during the acute phase (baseline) and longitudinally (baseline/6 months) between unrecovered (greater or unchanged pain and disability), partially recovered (improved but not recovered pain and/or disability), and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of sensory sensitivity alone, and with psychological and sleep data, using hierarchical clustering and related the clusters to outcome (pain/disability) at 3 and 6 months. No sensory measure at either time point differed between groups. Two subgroups were identified that associated with more ("high sensitivity") or less ("high sensitivity and negative psychological state") recovery. These data seem to suggest that central sensitization during the acute phase resolves for many patients, but is a precursor to the transition to chronicity when combined with other psychological features. PERSPECTIVE: Central sensitization signs during early acute LBP does not necessarily precede poor outcome, but may be sustained in conjunction with other psychological factors and facilitate pain persistence.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.BBI.2016.10.003
Abstract: Systemic inflammation is linked with development and persistence of many pathological pain states. Although chronic phase inflammatory responses are well reported, the acute phase has received limited attention. Here we investigated circulating pro-inflammatory cytokines and C-reactive protein (CRP), and explored their relationships with symptom severity and other factors in acute low back pain (LBP). Ninety-nine in iduals within two weeks of onset of acute LBP and 55 pain-free controls completed questionnaires related to their pain (visual analogue scale, VAS) and disability, behaviour, sleep quality and psychological status. CRP, interleukin-6 (IL-6), tumor necrosis factor (TNF) and interleukin-1β (IL-1β) were measured from serum s les. Biomarkers were compared between LBP and control participants, and in a separate analysis, for those with "high-pain" (VAS ⩾4) and "low-pain" (VAS <4). The relationships between biomarkers and all other variables, including other cytokines/CRP were assessed. CRP was higher in LBP than controls and in those with high- than low-pain (p<0.01). IL-6 was higher in those with high- than low-pain (p<0.05), but not controls. Various pain and non-pain factors were associated with each biomarker differently. These findings suggest systemic CRP and IL-6 are important contributors to inflammation in the early post-onset phase of LBP and that various factors can shape these responses.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2020
DOI: 10.1186/S13104-020-05356-Z
Abstract: Low back pain (LBP) is one of the most disabling and costly conditions worldwide. It remains unclear why many in iduals experience persistent and recurrent symptoms after an acute episode whereas others do not. A longitudinal cohort study was established to address this problem. We aimed to (1) evaluate whether promising and potentially modifiable biological, psychological, social and behavioural factors, along with their possible interactions, predict LBP outcome after an acute episode (2) compare these factors between in iduals with and without acute LBP and (3) evaluate the time-course of changes in these factors from LBP onset. This paper outlines the methodology and compares baseline characteristics between acute LBP and control, and LBP participants with and without follow-up. 133 in iduals with acute LBP and 74 pain-free in iduals participated. Bio-psycho-social and behavioural measures were collected at baseline and 3-monthly for 12 months (LBP) or 3 months (control). Pain and disability were recorded fortnightly. Baseline characteristics were mostly similar between those who did and did not return for follow-up. Initial analyses of this cohort have revealed important insights into the pathways involved in acute-to-chronic LBP. These and future findings will provide new targets for treatment and prevention of persistent and recurrent LBP.
Publisher: Elsevier BV
Date: 10-2018
Publisher: Springer Science and Business Media LLC
Date: 19-02-2018
DOI: 10.1007/S00586-018-5490-7
Abstract: Prospective longitudinal study. To determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of low back pain (LBP) differ between in iduals who did and did not recover by 6 months and to identify sub-groups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery. Systemic inflammation is observed in chronic LBP and may contribute to the transition from acute to persistent LBP. Longitudinal studies are required to determine whether changes present early or develop over time. Psychological and/or sleep-related factors may be related. In iduals within 2 weeks of onset of acute LBP (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP, tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1β, and completed questionnaires related to pain, disability, sleep, and psychological status. LBP participants repeated measurements at 6 months. Biomarkers were compared between LBP and control participants at baseline, and in longitudinal (baseline/6 months) analysis, between unrecovered (≥pain and disability), partially recovered (reduced pain and/or disability) and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of inflammatory, psychological, sleep, and pain data using hierarchical clustering and related the clusters to recovery (% change in pain) at 6 months. CRP was higher in acute LBP than controls at baseline. In LBP, baseline CRP was higher in the recovered than non-recovered groups. Conversely, TNF was higher at both time-points in the non-recovered than recovered groups. Two sub-groups were identified that associated with more ("inflammatory oor sleep") or less ("high TNF/depression") recovery. This is the first evidence of a relationship between an "acute-phase" systemic inflammatory response and recovery at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but specific elevation of TNF, along with depressive symptoms, was associated with bad recovery. Depression and TNF may have a two-way relationship. These slides can be retrieved under Electronic Supplementary Material.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.SPINEE.2021.09.006
Abstract: In idual characteristics can influence outcomes after injury. Our previous work in in iduals with early-acute low back pain (LBP) identified subgroups (clusters) with specific biopsychosocial features that recovered poorly or well by 6 months. This study extends on that work by revealing the short- and long-term trajectories of recovery and systemic inflammation of these participant clusters: (1) "inflammatory & poor sleep" (Cluster 1), "high TNF & depression" (Cluster 2), "high pain & high pain-related fear" (Cluster 3), and "low pain & low pain-related fear" (Cluster 4). Longitudinal cohort study. Eighty-three in iduals within 2 weeks of an acute episode of LBP - grouped into their a priori-defined cluster. General participant characteristics (sex, age, body mass index, smoking history, previous LBP history) self-reported LBP (0-10 numerical rating scale, LBP-related disability (Roland-Morris Disability Questionnaire), depression (Center for Epidemiological Studies Depression Scale, pain catastrophizing (Pain Catastrophizing Scale), fear avoidance (Fear Avoidance Beliefs Questionnaire), pain self-efficacy (Pain Self-Efficacy Questionnaire), and sleep (Pittsburgh Sleep Quality Index) systemic inflammatory biomarkers (C-reactive protein [CRP], interleukin-6 [IL-6], interleukin-1β, tumor necrosis factor [TNF]). Participants provided blood for the measurement of CRP/cytokines, and completed questionnaires related to their pain/disability, psychological and sleep status. Blood measures were repeated 3-monthly for 9 months, and pain/disability were self-reported fortnightly for 12 months. Recovery (change in pain) and CRP/cytokines were longitudinally compared between clusters using mixed-models. Associations between baseline factors and follow-up CRP/cytokines levels were assessed with multiple regression. Clusters 1 and 2 were associated, but oppositely, with recovery over the 12-months. Cluster 1 reported most recovery at every 3-monthly interval, whereas Cluster 2 reported least recovery. Cluster 1 had elevated CRP (and IL-6) at baseline that continued to decrease from 3 to 9 months. TNF was elevated early and persistently in Cluster 2. Baseline factors other than inflammation generally failed to predict follow-up inflammation. Findings support the early role of CRP (and perhaps IL-6) in control of inflammation and recovery, and a pathological role of persistent TNF overexpression, which may be perpetuated by depressive-like behaviors.
Publisher: Elsevier BV
Date: 11-2019
Publisher: Springer Science and Business Media LLC
Date: 13-04-2023
Publisher: University of Queensland Library
Publisher: MDPI AG
Date: 07-07-2021
DOI: 10.3390/IJMS22147299
Abstract: Musculoskeletal conditions are known to involve biological, psychological, social and, often, lifestyle elements. However, these domains are generally considered in isolation from each other. This siloed approach is unlikely to be adequate to understand the complexity of these conditions and likely explains a major component of the disappointing effects of treatment. This paper presents a hypothesis that aims to provide a foundation to understand the interaction and integration between these domains. We propose a hypothesis that provides a plausible link between psychology and lifestyle factors with tissue level effects (such as connective tissue dysregulation/accumulation) in musculoskeletal conditions that is founded on understanding the molecular basis for interaction between systemic and local inflammation. The hypothesis provides plausible and testable links between mind and body, for which empirical evidence can be found for many aspects. We present this hypothesis from the perspective of connective tissue biology and pathology (fibrosis), the role of inflammation locally (tissue level), and how this inflammation is shaped by systemic inflammation through bidirectional pathways, and various psychological and lifestyle factors via their influence on systemic inflammation. This hypothesis provides a foundation for new consideration of the development and refinement of personalized multidimensional treatments for in iduals with musculoskeletal conditions.
Publisher: Springer Science and Business Media LLC
Date: 04-08-2023
DOI: 10.1038/S41413-023-00280-X
Abstract: Low back pain (LBP) is the world’s leading cause of disability and is increasing in prevalence more rapidly than any other pain condition. Intervertebral disc (IVD) degeneration and facet joint osteoarthritis (FJOA) are two common causes of LBP, and both occur more frequently in elderly women than in other populations. Moreover, osteoarthritis (OA) and OA pain, regardless of the joint, are experienced by up to twice as many women as men, and this difference is lified during menopause. Changes in estrogen may be an important contributor to these pain states. Receptors for estrogen have been found within IVD tissue and nearby joints, highlighting the potential roles of estrogen within and surrounding the IVDs and joints. In addition, estrogen supplementation has been shown to be effective at ameliorating IVD degeneration and OA progression, indicating its potential use as a therapeutic agent for people with LBP and OA pain. This review comprehensively examines the relationship between estrogen and these pain conditions by summarizing recent preclinical and clinical findings. The potential molecular mechanisms by which estrogen may relieve LBP associated with IVD degeneration and FJOA and OA pain are discussed.
Publisher: Oxford University Press (OUP)
Date: 31-03-2020
DOI: 10.1093/PM/PNAA052
Abstract: Cytokines such as tumor necrosis factor (TNF) contribute to the transition from acute to persistent pain. Despite increasing incidence of obesity and its linkage with chronic pain and inflammation, cytokines predominantly produced by adipose tissue (adipokines) have received little attention. Here we aimed to explore the longitudinal trajectory of adipokines from the onset of acute low back pain (LBP) and identify combinations of adipokines and/or other features that predict outcome. In iduals with acute LBP (less than two weeks after onset) who had either recovered (no pain, N = 15) or remained unrecovered (no reduction/increase in pain, N = 13) at six months and 15 controls were retrospectively selected from a larger prospective cohort. Participants provided blood for the measurement of TNF, interleukin-6 (IL-6), resistin, visfatin, adiponectin, leptin, and C-reactive protein (CRP), and completed questionnaires related to pain/disability, depression, and sleep at baseline. LBP participants repeated measurements at six months. Compared with controls, acute LBP in iduals had higher TNF and CRP but lower adiponectin. In LBP, unrecovered in iduals had higher TNF at both time points, but lower CRP at baseline and leptin at six months. Although combined low CRP, high TNF, and depressive symptoms at baseline predicted poor recovery, the primary adipokines leptin, resistin, visfatin, and adiponectin did not. Primary adipokines did not add to the prediction of poor LBP outcome that has been identified for the combination of low CRP, high TNF, and depressive symptoms in acute LBP. Whether adipokines play a role in LBP persistence in overweight/obese in iduals requires investigation.
Publisher: Springer Science and Business Media LLC
Date: 08-02-2019
DOI: 10.1007/S00586-019-05902-9
Abstract: Chronic low back pain causes structural remodelling and inflammation in the multifidus muscle. Collagen expression is increased in the multifidus of humans with lumbar disc degeneration. However, the extent and mechanisms underlying the increased fibrotic activity in the multifidus are unknown. Physical activity reduces local inflammation that precedes multifidus fibrosis during intervertebral disc degeneration (IDD), but its effect on amelioration of fibrosis is unknown. This study aimed to assess the development of fibrosis and its underlying genetic network during IDD and the impact of physical activity. Wild-type and SPARC-null mice were either sedentary or housed with a running wheel, to allow voluntary physical activity. At 12 months of age, IDD was assessed with MRI, and multifidus muscle s les were harvested from L2 to L6. In SPARC-null mice, the L1/2 and L3/4 discs had low and high levels of IDD, respectively. Thus, multifidus s les from L2 and L4 were allocated to low- and high-IDD groups compared to assess the effects of IDD and physical activity on connective tissue and fibrotic genes. High IDD was associated with greater connective tissue thickness and dysregulation of collagen-III, fibronectin, CTGF, substance P, TIMP1 and TIMP2 in the multifidus muscle. Physical activity attenuated the IDD-dependent increased connective tissue thickness and reduced the expression of collagen-I, fibronectin, CTGF, substance P, MMP2 and TIMP2 in SPARC-null animals and wild-type mice. Collagen-III and TIMP1 were only reduced in wild-type animals. These data reveal the fibrotic networks that promote fibrosis in the multifidus muscle during chronic IDD. Furthermore, physical activity is shown to reduce fibrosis and regulate the fibrotic gene network. These slides can be retrieved under Electronic Supplementary Material.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JPAIN.2014.11.005
Abstract: Reduced pain perception during painful stimulation to another body region (ie, conditioned pain modulation [CPM]) is considered important for pain modulation and development of pain disorders. The various methods used to study CPM limit comparison of findings. We investigated the influence of key methodologic variations on CPM and the properties of CPM when the back is used for the test stimulus or the conditioning stimulus (CS). Two different test stimuli (pressure pain threshold and pain response to suprathreshold heat [Pain-45, ie, pain rated at 45 on a 0-100 numeric rating scale]) were assessed before and during application of a noxious or non-noxious (sham) CS. Eight blocks of trials varied the anatomic location (back and forearms) and arrangement (body side) of the stimuli. Pressure pain threshold (as the test stimulus) increased during application of noxious, but not non-noxious, CS when stimuli were applied to opposite body sides or heterotopic sites on one body side. Inconsistent with pain-induced CPM, Pain-45 decreased during both noxious and non-noxious CS. These findings indicate that 1) pressure pain threshold can be more confidently interpreted with respect to CPM evoked by a painful stimulus than Pain-45, 2) the back and forearm are equally effective as sites for stimuli, and 3) stimuli arrangement does not influence CPM, except for identical anatomic regions on the same body side. This study indicates that pressure pain threshold as the test stimulus provides a more valid measure of pain-induced CPM than pain response to a suprathreshold heat stimulus. Induction and magnitude of CPM is independent of stimuli arrangement, as long as ipsilateral homotopic sites are avoided. These findings clarify methods to study CPM.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.JPAIN.2018.02.017
Abstract: Generalized hyperalgesia and impaired pain modulation are reported in chronic low back pain (LBP). Few studies have tested whether these features are present in the acute phase. This study aimed to test for differences in pain presentation in early-acute LBP and evaluate the potential contribution of other factors to variation in sensitivity. In iduals within 2 weeks of onset of acute LBP (n = 126) and pain-free controls (n = 74) completed questionnaires related to their pain, disability, behavior, and psychological status before undergoing conditioned pain modulation (CPM) and pain threshold (heat, cold, and pressure) testing at the back and forearm/thumb. LBP participants were more sensitive to heat and cold at both sites and pressure at the back than controls, without differences in CPM. Only those with high-pain (numeric rating scale ≥4) were more sensitive to heat at the forearm and pressure at the back. Four subgroups with distinct features were identified: "high sensitivity," "low CPM efficacy," "high sensitivity/low CPM efficacy," and "low sensitivity/high CPM efficacy." Various factors such as sleep and alcohol were associated with each pain measure. Results provide evidence for generalized hyperalgesia in many, but not all, in iduals during acute LBP, with variation accounted for by several factors. Specific pain phenotypes provide candidate features to test in longitudinal studies of LBP outcome. Sensory changes indicative of increased/decreased central processing of pain and nociceptive input presented differently between in iduals with acute LBP and were related to factors such as sleep and alcohol. This may underlie variation in outcome and suggest potential for early identification of in iduals with poor long-term outcome.
Publisher: Public Library of Science (PLoS)
Date: 12-05-2022
DOI: 10.1371/JOURNAL.PONE.0268381
Abstract: Postural control of the trunk is critical for performance of everyday activities and the health of spinal tissues. Although some studies report that in iduals with low back pain (LBP) have poorer/compromised postural control than pain-free in iduals when sitting on an unstable surface, others do not. Analyses commonly lack the statistical power to evaluate the relevance of features that could impact the performance of postural control, such as sex, age, anthropometrics, pain intensity or disability. This paper outlines a protocol for a systematic review with an in idual participant data (IPD) meta-analysis that aims to synthesise the evidence and evaluate differences of postural control measures between in iduals with and without LBP during unstable sitting. A systematic review with IPD meta-analysis will be conducted according to PRISMA-IPD guidelines. To identify relevant studies, electronic databases and the reference lists of included articles will be screened. Unstable seat movements are derived from centre of pressure (CoP) data using a force plate or angle of the seat using motion systems/sensors. The comprehensiveness of reporting and methodological quality of included studies will be assessed. Analysis will involve a descriptive analysis to synthesise the findings of all included studies and a quantitative synthesis using two-stage IPD meta-analysis of studies that include both in iduals with and without LBP for which IPD set can be obtained from authors. Analyses will include consideration of confounding variables. Exemption from ethical approval was obtained for this review (University of Queensland, ID: 2019003026). PROSPERO ID: CRD42021124658 .
Publisher: Springer Science and Business Media LLC
Date: 30-01-2020
DOI: 10.1186/S12891-020-3085-Z
Abstract: Musculoskeletal disorders can result from prolonged repetitive and/or forceful movements. Performance of an upper extremity high repetition high force task increases serum pro-inflammatory cytokines and upper extremity sensorimotor declines in a rat model of work-related musculoskeletal disorders. Since one of the most efficacious treatments for musculoskeletal pain is exercise, this study investigated the effectiveness of treadmill running in preventing these responses. Twenty-nine young adult female Sprague-Dawley rats were used. Nineteen were trained for 5 weeks to pull a lever bar at high force (15 min/day). Thirteen went on to perform a high repetition high force reaching and lever-pulling task for 10 weeks (10-wk HRHF 2 h/day, 3 days/wk). From this group, five were randomly selected to undergo forced treadmill running exercise (TM) during the last 6 weeks of task performance (10-wk HRHF+TM, 1 h/day, 5 days/wk). Results were compared to 10 control rats and 6 rats that underwent 6 weeks of treadmill running following training only (TR-then-TM). Voluntary task and reflexive sensorimotor behavioral outcomes were assessed. Serum was assayed for inflammatory cytokines and corticosterone, reach limb median nerves for CD68+ macrophages and extraneural thickening, and reach limb flexor digitorum muscles and tendons for pathological changes. 10-wk HRHF rats had higher serum levels of IL-1α, IL-1β and TNFα, than control rats. In the 10-wk HRHF+TM group, IL-1β and TNFα were lower, whereas IL-10 and corticosterone were higher, compared to 10-wk HRHF only rats. Unexpectedly, several voluntary task performance outcomes (grasp force, reach success, and participation) worsened in rats that underwent treadmill running, compared to untreated 10-wk HRHF rats. Examination of forelimb tissues revealed lower cellularity within the flexor digitorum epitendon but higher numbers of CD68+ macrophages within and extraneural fibrosis around median nerves in 10-wk HRHF+TM than 10-wk HRHF rats. Treadmill running was associated with lower systemic inflammation and moderate tendinosis, yet higher median nerve inflammation/fibrosis and worse task performance and sensorimotor behaviors. Continued loading of the injured tissues in addition to stress-related factors associated with forced running/exercise likely contributed to our findings.
No related grants have been discovered for David Klyne.