Early career postdoctoral researcher with an interest in mechanisms that may translate into potential therapeutic targets, namely: what takes place to effect poor recovery and the development of persistent pain; what is involved in the maintenance of persistent pain; and neuroimmune and endocrine factors in pain.
My doctoral thesis investigated the role of inflammation in recovery from fracture and its potential role in the development of complex regional pain syndrome (CRPS). Supervisors: Jarred Younger
The brain plays a key role in CRPS. A widely-‐studied brain region in pain research is the prima... more The brain plays a key role in CRPS. A widely-‐studied brain region in pain research is the primary somatosensory cortex (S1), a somatotopic map of our body’s surface which funcEonally reorganises in pain [1]. Changes in the S1 representaEon of the CRPS-‐affected body part have contributed to new CRPS treatments, e.g. graded motor imagery. This systemaEc review and meta-‐analysis aimed to determine whether CRPS is associated with: a) a change in the size of the S1 representaEon of the affected body part; b) altered S1 acEvity, in terms of acEvaEon levels and latency of responses.
Adult neurogenesis represents a mature brain’s capacity to integrate newly generated neurons into... more Adult neurogenesis represents a mature brain’s capacity to integrate newly generated neurons into functional circuits. Impairment of neurogenesis contributes to the pathophysiology of various mood and cognitive disorders such as depression and Alzheimer’s Disease. The hippocampal neurogenic niche hosts neural progenitors, glia, and vasculature, which all respond to intrinsic and environmental cues, helping determine their current state and ultimate fate. In this article we focus on the major immune communication pathways and mechanisms through which glial cells sense, interact with, and modulate the neurogenic niche. We pay particular attention to those related to the sensing of and response to innate immune danger signals. Receptors for danger signals were first discovered as a critical component of the innate immune system response to pathogens but are now also recognized to play a crucial role in modulating non-pathogenic sterile inflammation. In the neurogenic niche, viable, str...
The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life.... more The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells (NSCs), are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associated cognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has been the subject of intense investigation, generating both excitement and controversy. Identifying the core molecular machinery responsible for NSC preservation is of fundamental importance if we are to use neurogenesis to halt or reverse hippocampal age-related pathology. Here, we briefly overview the most frequently used mouse models to study hippocampal neurogenesis and then focus on a unique mouse model that allows NSC-specific studies based on their unique expression of lunatic fringe (Lfng). The Lfng-eGFP and Lfng(BAC)-CreERT2;RCL-tdT transgenic mice provide us with an excellent tool to resolve long-standing questions regarding the properties of NSCs, such as their specific molecular composition, potency, and plasticity, in isolation from any other cell in the hippocampal neurogenic niche.
Treatment-related sequelae following cranial irradiation have life changing impacts for patients ... more Treatment-related sequelae following cranial irradiation have life changing impacts for patients and their caregivers. Characterization of the basic response of human brain tissue to irradiation has been difficult due to a lack of preclinical models. The direct study of human brain tissue in vitro is becoming possible due to advances in stem cell biology, neuroscience, and tissue engineering with the development of organoids as novel model systems which enable experimentation with human tissue models. We sought to establish a cerebral organoid (CO) model to study the radioresponse of normal human brain tissue. COs were grown using human induced pluripotent stem cells and a modified Lancaster protocol. Compositional analysis during development of the COs showed expected populations of neurons and glia. We confirmed a population of microglia-like cells within the model positive for the makers Iba1 and CD68. After 2-months of maturation, COs were irradiated to 0, 10, and 20 Gy using a ...
The Journal of orthopaedic and sports physical therapy, Jan 12, 2018
Study Design Secondary analysis of a prospective cohort study. Background Worldwide, the incidenc... more Study Design Secondary analysis of a prospective cohort study. Background Worldwide, the incidence of wrist fracture is increasing. There are currently no externally validated prognostic models to inform early decision making for these patients. Objectives To develop and validate a prognostic model from a comprehensive range of candidate prognostic factors that can identify patients at risk of developing persistent pain following wrist or hand fracture. Methods We developed and validated a prognostic model using secondary data derived from a prospective cohort study (n=715) with recruitment sites in three metropolitan hospitals in Sydney, Australia. The primary outcome was persistent pain four months following the injury. We used a backwards stepwise regression analysis to develop the model in two hospitals (n=408) and externally validate it in a third hospital (n=307). To determine the accuracy of the model we assessed calibration and discrimination in accordance with the PROGRESS ...
The journal of pain : official journal of the American Pain Society, Jan 14, 2017
The purpose of this longitudinal blood sampling study was to examine relationships between sex ho... more The purpose of this longitudinal blood sampling study was to examine relationships between sex hormones and fibromyalgia pain. Eight women meeting case definition criteria for fibromyalgia provided venous blood samples and reported their fibromyalgia pain severity over 25 consecutive days. All women exhibited normal menstrual cycles and were not taking oral contraceptives. Cortisol, and the sex hormones estradiol, progesterone, and testosterone, were assayed from serum. A linear mixed model was used to determine if fluctuations of sex hormones were associated with changes in pain severity. In the entire sample, day-to-day changes in both progesterone (p = 0.002) and testosterone (p = 0.015) were significantly and inversely correlated with pain severity. There was no relationship between estradiol and pain (p = 0.551) or cortisol and pain (p = 0.633). These results suggest that progesterone and testosterone play a protective role in fibromyalgia pain severity. Sex and other hormones ...
To assess the effects of preclinic group education sessions and system redesign on tertiary pain ... more To assess the effects of preclinic group education sessions and system redesign on tertiary pain medicine units and patient outcomes. Prospective cohort study. Two public hospital multidisciplinary pain medicine units. People with persistent pain. A system redesign from a "traditional" model (initial individual medical appointments) to a model that delivers group education sessions prior to individual appointments. Based on Patient Triage Questionnaires patients were scheduled to attend Self-Training Educative Pain Sessions (STEPS), a two day eight hour group education program, followed by optional patient-initiated clinic appointments. Number of patients completing STEPS who subsequently requested individual outpatient clinic appointment(s); wait-times; unit cost per new patient referred; recurrent health care utilization; patient satisfaction; Global Perceived Impression of Change (GPIC); and utilized pain management strategies. Following STEPS 48% of attendees requested individual outpatient appointments. Wait times reduced from 105.6 to 16.1 weeks at one pain unit and 37.3 to 15.2 weeks at the second. Unit cost per new patient appointed reduced from $1,805 Australian Dollars (AUD) to AUD$541 (for STEPS). At 3 months, patients scored their satisfaction with "the treatment received for their pain" more positively than at baseline (change score=0.88; P=0.0003), GPIC improved (change score=0.46; P<0.0001) and mean number of active strategies utilized increased by 4.12 per patient (P=0.0004). The introduction of STEPS was associated with reduced wait-times and costs at public pain medicine units and increased both the use of active pain management strategies and patient satisfaction.
Background and purpose: Orofacial pain disorders are relatively uncommon and present a substantia... more Background and purpose: Orofacial pain disorders are relatively uncommon and present a substantial diagnostic challenge. In this case report we document the diagnosis and management of a patient with hemifacial pain who was referred to an interdisciplinary pain medicine unit. The purpose of this case report is twofold. First, we present complex regional pain syndrome (CRPS) as a potential differential diagnosis in cases of facial pain. Second, we demonstrate that contemporary management approaches for distal extremity CRPS can be successfully adapted to treat people with CRPS of the facial region.
Case description: The patient presented with hemifacial pain and concomitant motor and autonomic symptoms following a small laceration of the eyelid. Extensive specialist medical evaluations were undertaken to exclude an underlying structural pathology. Following detailed clinical assessments by a physical therapist, pain physician, and clinical psychologist, a diagnosis was made of CRPS involving the face.
Outcomes: The patient's pain was largely unresponsive to pharmacological agents. A modified graded motor imagery (GMI) program, together with desensitisation and discrimination training were commenced by the physical therapist and clinical psychologist. A positive clinical response was indicated by a decrease in allodynia, normalisation of motor control, and regained function in activities of daily living.
Discussion: Complex regional pain syndrome (CRPS) is an infrequently reported differential diagnosis that can be considered in patients presenting with persistent facial pain. In this case report, we highlight how careful examination and clinical decision making led us to employ an innovative therapeutic strategy to manage a challenging condition.
Background: Gulf War Illness (GWI) is a clinically heterogeneous chronic condition that affects m... more Background: Gulf War Illness (GWI) is a clinically heterogeneous chronic condition that affects many veterans of the 1990–1991 Persian Gulf War. One of the most prevalent and debilitating symptoms of GWI is abnormal fatigue. The mechanisms underlying GWI generally, and fatigue symptoms specifically, have yet to be conclusively identified, although immune system abnormalities are suspected to be involved. The first goal of this immune monitoring study was to determine if GWI is associated with higher absolute levels and daily variability of pro-inflammatory immune factors. The second goal was to explore the relationship between day-to-day immune marker fluctuations and daily self-reported fatigue severity. Methods: We recruited veterans with GWI and healthy veteran control (HV) participants to provide self-reported fatigue severity data and blood samples, over 25 consecutive days. We profiled inflammatory processes by using a longitudinal, daily immune-monitoring approach. For each day, serum cytokine and chemokine concentrations were determined using multiplex assays. Results: Seven veterans with GWI and eight healthy veteran control (HV) participants completed the study protocol. We found that GWI was associated with higher variability in the expression of eotaxin-1 (p < 0.001). For GWI participants, higher fatigue severity days were associated with greater IL-1β (p = 0.008) and IL-15 (p < 0.001). Conclusions: Our findings provide preliminary evidence that the immune system is involved in the pathophysiology of GWI. Longitudinal immune profiling approaches may be helpful in discovering targets for novel therapies in conditions such as GWI.
Upper limb fracture is a common musculoskeletal injury that can lead to marked pain-related disab... more Upper limb fracture is a common musculoskeletal injury that can lead to marked pain-related disability. Unlike other common painful musculoskeletal conditions, such as low back pain, little consideration has been given to the role that psychological variables may play in explaining the relationship between pain and disability during early fracture recovery. This cross-sectional study aimed to determine if psychological distress (symptoms of depression, anxiety, and/or stress) mediate the relationship between pain and disability in acute hand/wrist fractures. Self-report data from a consecutive sample of 594 patients with acute hand/wrist fracture were used. Mediation analyses were conducted to determine the role of depression, anxiety, and stress in the relationship between pain and disability, controlling for relevant demographic and fracture related variables. Depression and stress, but not anxiety, significantly mediated the relationship between pain and disability. That is, while each psychological distress variable was associated with pain (P<0.001), only depression (b1=0.27, P=0.03) and stress (b3=0.23, P=0.02) were significantly associated with disability, and fulfilled recommended criteria for establishing a mediating variable. Elevated depression and stress, but not anxiety, explain the relationship between pain and disability and may be novel targets for interventions designed to reduce pain-related disability after upper limb fracture. This study presents the mediating effect of psychological distress on the relationship between pain and disability in acute upper limb fracture. These factors may be novel targets for interventions designed to reduce pain-related disability after acute fracture.
Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as ... more Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone’s better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.
The brain plays a key role in CRPS. A widely-‐studied brain region in pain research is the prima... more The brain plays a key role in CRPS. A widely-‐studied brain region in pain research is the primary somatosensory cortex (S1), a somatotopic map of our body’s surface which funcEonally reorganises in pain [1]. Changes in the S1 representaEon of the CRPS-‐affected body part have contributed to new CRPS treatments, e.g. graded motor imagery. This systemaEc review and meta-‐analysis aimed to determine whether CRPS is associated with: a) a change in the size of the S1 representaEon of the affected body part; b) altered S1 acEvity, in terms of acEvaEon levels and latency of responses.
Adult neurogenesis represents a mature brain’s capacity to integrate newly generated neurons into... more Adult neurogenesis represents a mature brain’s capacity to integrate newly generated neurons into functional circuits. Impairment of neurogenesis contributes to the pathophysiology of various mood and cognitive disorders such as depression and Alzheimer’s Disease. The hippocampal neurogenic niche hosts neural progenitors, glia, and vasculature, which all respond to intrinsic and environmental cues, helping determine their current state and ultimate fate. In this article we focus on the major immune communication pathways and mechanisms through which glial cells sense, interact with, and modulate the neurogenic niche. We pay particular attention to those related to the sensing of and response to innate immune danger signals. Receptors for danger signals were first discovered as a critical component of the innate immune system response to pathogens but are now also recognized to play a crucial role in modulating non-pathogenic sterile inflammation. In the neurogenic niche, viable, str...
The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life.... more The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells (NSCs), are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associated cognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has been the subject of intense investigation, generating both excitement and controversy. Identifying the core molecular machinery responsible for NSC preservation is of fundamental importance if we are to use neurogenesis to halt or reverse hippocampal age-related pathology. Here, we briefly overview the most frequently used mouse models to study hippocampal neurogenesis and then focus on a unique mouse model that allows NSC-specific studies based on their unique expression of lunatic fringe (Lfng). The Lfng-eGFP and Lfng(BAC)-CreERT2;RCL-tdT transgenic mice provide us with an excellent tool to resolve long-standing questions regarding the properties of NSCs, such as their specific molecular composition, potency, and plasticity, in isolation from any other cell in the hippocampal neurogenic niche.
Treatment-related sequelae following cranial irradiation have life changing impacts for patients ... more Treatment-related sequelae following cranial irradiation have life changing impacts for patients and their caregivers. Characterization of the basic response of human brain tissue to irradiation has been difficult due to a lack of preclinical models. The direct study of human brain tissue in vitro is becoming possible due to advances in stem cell biology, neuroscience, and tissue engineering with the development of organoids as novel model systems which enable experimentation with human tissue models. We sought to establish a cerebral organoid (CO) model to study the radioresponse of normal human brain tissue. COs were grown using human induced pluripotent stem cells and a modified Lancaster protocol. Compositional analysis during development of the COs showed expected populations of neurons and glia. We confirmed a population of microglia-like cells within the model positive for the makers Iba1 and CD68. After 2-months of maturation, COs were irradiated to 0, 10, and 20 Gy using a ...
The Journal of orthopaedic and sports physical therapy, Jan 12, 2018
Study Design Secondary analysis of a prospective cohort study. Background Worldwide, the incidenc... more Study Design Secondary analysis of a prospective cohort study. Background Worldwide, the incidence of wrist fracture is increasing. There are currently no externally validated prognostic models to inform early decision making for these patients. Objectives To develop and validate a prognostic model from a comprehensive range of candidate prognostic factors that can identify patients at risk of developing persistent pain following wrist or hand fracture. Methods We developed and validated a prognostic model using secondary data derived from a prospective cohort study (n=715) with recruitment sites in three metropolitan hospitals in Sydney, Australia. The primary outcome was persistent pain four months following the injury. We used a backwards stepwise regression analysis to develop the model in two hospitals (n=408) and externally validate it in a third hospital (n=307). To determine the accuracy of the model we assessed calibration and discrimination in accordance with the PROGRESS ...
The journal of pain : official journal of the American Pain Society, Jan 14, 2017
The purpose of this longitudinal blood sampling study was to examine relationships between sex ho... more The purpose of this longitudinal blood sampling study was to examine relationships between sex hormones and fibromyalgia pain. Eight women meeting case definition criteria for fibromyalgia provided venous blood samples and reported their fibromyalgia pain severity over 25 consecutive days. All women exhibited normal menstrual cycles and were not taking oral contraceptives. Cortisol, and the sex hormones estradiol, progesterone, and testosterone, were assayed from serum. A linear mixed model was used to determine if fluctuations of sex hormones were associated with changes in pain severity. In the entire sample, day-to-day changes in both progesterone (p = 0.002) and testosterone (p = 0.015) were significantly and inversely correlated with pain severity. There was no relationship between estradiol and pain (p = 0.551) or cortisol and pain (p = 0.633). These results suggest that progesterone and testosterone play a protective role in fibromyalgia pain severity. Sex and other hormones ...
To assess the effects of preclinic group education sessions and system redesign on tertiary pain ... more To assess the effects of preclinic group education sessions and system redesign on tertiary pain medicine units and patient outcomes. Prospective cohort study. Two public hospital multidisciplinary pain medicine units. People with persistent pain. A system redesign from a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;traditional&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; model (initial individual medical appointments) to a model that delivers group education sessions prior to individual appointments. Based on Patient Triage Questionnaires patients were scheduled to attend Self-Training Educative Pain Sessions (STEPS), a two day eight hour group education program, followed by optional patient-initiated clinic appointments. Number of patients completing STEPS who subsequently requested individual outpatient clinic appointment(s); wait-times; unit cost per new patient referred; recurrent health care utilization; patient satisfaction; Global Perceived Impression of Change (GPIC); and utilized pain management strategies. Following STEPS 48% of attendees requested individual outpatient appointments. Wait times reduced from 105.6 to 16.1 weeks at one pain unit and 37.3 to 15.2 weeks at the second. Unit cost per new patient appointed reduced from $1,805 Australian Dollars (AUD) to AUD$541 (for STEPS). At 3 months, patients scored their satisfaction with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;the treatment received for their pain&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; more positively than at baseline (change score=0.88; P=0.0003), GPIC improved (change score=0.46; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and mean number of active strategies utilized increased by 4.12 per patient (P=0.0004). The introduction of STEPS was associated with reduced wait-times and costs at public pain medicine units and increased both the use of active pain management strategies and patient satisfaction.
Background and purpose: Orofacial pain disorders are relatively uncommon and present a substantia... more Background and purpose: Orofacial pain disorders are relatively uncommon and present a substantial diagnostic challenge. In this case report we document the diagnosis and management of a patient with hemifacial pain who was referred to an interdisciplinary pain medicine unit. The purpose of this case report is twofold. First, we present complex regional pain syndrome (CRPS) as a potential differential diagnosis in cases of facial pain. Second, we demonstrate that contemporary management approaches for distal extremity CRPS can be successfully adapted to treat people with CRPS of the facial region.
Case description: The patient presented with hemifacial pain and concomitant motor and autonomic symptoms following a small laceration of the eyelid. Extensive specialist medical evaluations were undertaken to exclude an underlying structural pathology. Following detailed clinical assessments by a physical therapist, pain physician, and clinical psychologist, a diagnosis was made of CRPS involving the face.
Outcomes: The patient's pain was largely unresponsive to pharmacological agents. A modified graded motor imagery (GMI) program, together with desensitisation and discrimination training were commenced by the physical therapist and clinical psychologist. A positive clinical response was indicated by a decrease in allodynia, normalisation of motor control, and regained function in activities of daily living.
Discussion: Complex regional pain syndrome (CRPS) is an infrequently reported differential diagnosis that can be considered in patients presenting with persistent facial pain. In this case report, we highlight how careful examination and clinical decision making led us to employ an innovative therapeutic strategy to manage a challenging condition.
Background: Gulf War Illness (GWI) is a clinically heterogeneous chronic condition that affects m... more Background: Gulf War Illness (GWI) is a clinically heterogeneous chronic condition that affects many veterans of the 1990–1991 Persian Gulf War. One of the most prevalent and debilitating symptoms of GWI is abnormal fatigue. The mechanisms underlying GWI generally, and fatigue symptoms specifically, have yet to be conclusively identified, although immune system abnormalities are suspected to be involved. The first goal of this immune monitoring study was to determine if GWI is associated with higher absolute levels and daily variability of pro-inflammatory immune factors. The second goal was to explore the relationship between day-to-day immune marker fluctuations and daily self-reported fatigue severity. Methods: We recruited veterans with GWI and healthy veteran control (HV) participants to provide self-reported fatigue severity data and blood samples, over 25 consecutive days. We profiled inflammatory processes by using a longitudinal, daily immune-monitoring approach. For each day, serum cytokine and chemokine concentrations were determined using multiplex assays. Results: Seven veterans with GWI and eight healthy veteran control (HV) participants completed the study protocol. We found that GWI was associated with higher variability in the expression of eotaxin-1 (p < 0.001). For GWI participants, higher fatigue severity days were associated with greater IL-1β (p = 0.008) and IL-15 (p < 0.001). Conclusions: Our findings provide preliminary evidence that the immune system is involved in the pathophysiology of GWI. Longitudinal immune profiling approaches may be helpful in discovering targets for novel therapies in conditions such as GWI.
Upper limb fracture is a common musculoskeletal injury that can lead to marked pain-related disab... more Upper limb fracture is a common musculoskeletal injury that can lead to marked pain-related disability. Unlike other common painful musculoskeletal conditions, such as low back pain, little consideration has been given to the role that psychological variables may play in explaining the relationship between pain and disability during early fracture recovery. This cross-sectional study aimed to determine if psychological distress (symptoms of depression, anxiety, and/or stress) mediate the relationship between pain and disability in acute hand/wrist fractures. Self-report data from a consecutive sample of 594 patients with acute hand/wrist fracture were used. Mediation analyses were conducted to determine the role of depression, anxiety, and stress in the relationship between pain and disability, controlling for relevant demographic and fracture related variables. Depression and stress, but not anxiety, significantly mediated the relationship between pain and disability. That is, while each psychological distress variable was associated with pain (P<0.001), only depression (b1=0.27, P=0.03) and stress (b3=0.23, P=0.02) were significantly associated with disability, and fulfilled recommended criteria for establishing a mediating variable. Elevated depression and stress, but not anxiety, explain the relationship between pain and disability and may be novel targets for interventions designed to reduce pain-related disability after upper limb fracture. This study presents the mediating effect of psychological distress on the relationship between pain and disability in acute upper limb fracture. These factors may be novel targets for interventions designed to reduce pain-related disability after acute fracture.
Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as ... more Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone’s better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.
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Case description: The patient presented with hemifacial pain and concomitant motor and autonomic symptoms following a small laceration of the eyelid. Extensive specialist medical evaluations were undertaken to exclude an underlying structural pathology. Following detailed clinical assessments by a physical therapist, pain physician, and clinical psychologist, a diagnosis was made of CRPS involving the face.
Outcomes: The patient's pain was largely unresponsive to pharmacological agents. A modified graded motor imagery (GMI) program, together with desensitisation and discrimination training were commenced by the physical therapist and clinical psychologist. A positive clinical response was indicated by a decrease in allodynia, normalisation of motor control, and regained function in activities of daily living.
Discussion: Complex regional pain syndrome (CRPS) is an infrequently reported differential diagnosis that can be considered in patients presenting with persistent facial pain. In this case report, we highlight how careful examination and clinical decision making led us to employ an innovative therapeutic strategy to manage a challenging condition.
the 1990–1991 Persian Gulf War. One of the most prevalent and debilitating symptoms of GWI is abnormal fatigue.
The mechanisms underlying GWI generally, and fatigue symptoms specifically, have yet to be conclusively identified,
although immune system abnormalities are suspected to be involved. The first goal of this immune monitoring study
was to determine if GWI is associated with higher absolute levels and daily variability of pro-inflammatory immune
factors. The second goal was to explore the relationship between day-to-day immune marker fluctuations and daily
self-reported fatigue severity.
Methods: We recruited veterans with GWI and healthy veteran control (HV) participants to provide self-reported
fatigue severity data and blood samples, over 25 consecutive days. We profiled inflammatory processes by using a
longitudinal, daily immune-monitoring approach. For each day, serum cytokine and chemokine concentrations were
determined using multiplex assays.
Results: Seven veterans with GWI and eight healthy veteran control (HV) participants completed the study protocol.
We found that GWI was associated with higher variability in the expression of eotaxin-1 (p < 0.001). For GWI
participants, higher fatigue severity days were associated with greater IL-1β (p = 0.008) and IL-15 (p < 0.001).
Conclusions: Our findings provide preliminary evidence that the immune system is involved in the pathophysiology
of GWI. Longitudinal immune profiling approaches may be helpful in discovering targets for novel therapies in
conditions such as GWI.
This study presents the mediating effect of psychological distress on the relationship between pain and disability in acute upper limb fracture. These factors may be novel targets for interventions designed to reduce pain-related disability after acute fracture.
Case description: The patient presented with hemifacial pain and concomitant motor and autonomic symptoms following a small laceration of the eyelid. Extensive specialist medical evaluations were undertaken to exclude an underlying structural pathology. Following detailed clinical assessments by a physical therapist, pain physician, and clinical psychologist, a diagnosis was made of CRPS involving the face.
Outcomes: The patient's pain was largely unresponsive to pharmacological agents. A modified graded motor imagery (GMI) program, together with desensitisation and discrimination training were commenced by the physical therapist and clinical psychologist. A positive clinical response was indicated by a decrease in allodynia, normalisation of motor control, and regained function in activities of daily living.
Discussion: Complex regional pain syndrome (CRPS) is an infrequently reported differential diagnosis that can be considered in patients presenting with persistent facial pain. In this case report, we highlight how careful examination and clinical decision making led us to employ an innovative therapeutic strategy to manage a challenging condition.
the 1990–1991 Persian Gulf War. One of the most prevalent and debilitating symptoms of GWI is abnormal fatigue.
The mechanisms underlying GWI generally, and fatigue symptoms specifically, have yet to be conclusively identified,
although immune system abnormalities are suspected to be involved. The first goal of this immune monitoring study
was to determine if GWI is associated with higher absolute levels and daily variability of pro-inflammatory immune
factors. The second goal was to explore the relationship between day-to-day immune marker fluctuations and daily
self-reported fatigue severity.
Methods: We recruited veterans with GWI and healthy veteran control (HV) participants to provide self-reported
fatigue severity data and blood samples, over 25 consecutive days. We profiled inflammatory processes by using a
longitudinal, daily immune-monitoring approach. For each day, serum cytokine and chemokine concentrations were
determined using multiplex assays.
Results: Seven veterans with GWI and eight healthy veteran control (HV) participants completed the study protocol.
We found that GWI was associated with higher variability in the expression of eotaxin-1 (p < 0.001). For GWI
participants, higher fatigue severity days were associated with greater IL-1β (p = 0.008) and IL-15 (p < 0.001).
Conclusions: Our findings provide preliminary evidence that the immune system is involved in the pathophysiology
of GWI. Longitudinal immune profiling approaches may be helpful in discovering targets for novel therapies in
conditions such as GWI.
This study presents the mediating effect of psychological distress on the relationship between pain and disability in acute upper limb fracture. These factors may be novel targets for interventions designed to reduce pain-related disability after acute fracture.