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Gerdle B.,Pain and Rehabilitation Center | Forsgren M.F.,Linköping University | Bengtsson A.,Linköping University | Dahlqvist Leinhard O.,Linköping University | And 5 more authors.
European Journal of Pain (United Kingdom) | Year: 2013

Background and Methods: Fibromyalgia (FMS) has a prevalence of approximately 2% in the population. Central alterations have been described in FMS, but there is not consensus with respect to the role of peripheral factors for the maintenance of FMS. 31P Magnetic Resonance Spectroscopy (31P-MRS) has been used to investigate the metabolism of phosphagens in muscles of FMS patients, but the results in the literature are not in consensus. The aim was to investigate the quantitative content of phosphagens and pH in resting quadriceps muscle of patients with FMS (n = 19) and in healthy controls (Controls; n = 14) using 31P-MRS. It was also investigated whether the concentrations of these substances correlated with measures of pain and/or physical capacity. Results: Significantly lower concentrations of adenosine triphosphate (ATP) and phosphocreatinine (PCr; 28-29% lower) were found in FMS. No significant group differences existed with respect to inorganic phosphate (Pi), Pi/PCr and pH. The quadriceps muscle fat content was significantly higher in FMS than in Controls [FMS: 9.0 ± 0.5% vs. Controls: 6.6 ± 0.6%; (mean ± standard error); P = 0.005]. FMS had significantly lower hand and leg capacity according to specific physical test, but there were no group differences in body mass index, subjective activity level and in aerobic fitness. In FMS, the specific physical capacity in the leg and the hand correlated positively with the concentrations of ATP and PCr; no significant correlations were found with pain intensities. Conclusions: Alterations in intramuscular ATP, PCr and fat content in FMS probably reflect a combination of inactivity related to pain and dysfunction of muscle mitochondria. © 2013 European Federation of International Association for the Study of Pain Chapters.


Fornander L.,Linköping University | Ghafouri B.,Linköping University | Ghafouri B.,Pain and Rehabilitation Center | Lindahl M.,Linköping University | Graff P.,Linköping University
International Archives of Occupational and Environmental Health | Year: 2013

Purpose: Occurrence of airway irritation among indoor swimming pool personnel was investigated. The aims of this study were to assess trichloramine exposure levels and exhaled nitric oxide in relation to the prevalence of airway symptoms in swimming pool facilities and to determine protein effects in the upper respiratory tract. Methods: The presence of airway symptoms related to work was examined in 146 individuals working at 46 indoor swimming pool facilities. Levels of trichloramine, as well as exhaled nitric oxide, were measured in five facilities with high prevalence of airway irritation and four facilities with no airway irritation among the personnel. Nasal lavage fluid was collected, and protein profiles were determined by a proteomic approach. Results: 17 % of the swimming pool personnel reported airway symptoms related to work. The levels of trichloramine in the swimming pool facilities ranged from 0.04 to 0.36 mg/m3. There was no covariance between trichloramine levels, exhaled nitric oxide and prevalence of airway symptoms. Protein profiling of the nasal lavage fluid showed that the levels alpha-1-antitrypsin and lactoferrin were significantly higher, and S100-A8 was significantly lower in swimming pool personnel. Conclusions: This study confirms the occurrence of airway irritation among indoor swimming pool personnel. Our results indicate altered levels of innate immunity proteins in the upper airways that may pose as potential biomarkers. However, swimming pool facilities with high prevalence of airway irritation could not be explained by higher trichloramine exposure levels. Further studies are needed to clarify the environmental factors in indoor swimming pools that cause airway problems and affect the immune system. © 2012 Springer-Verlag.


Gerdle B.,Linköping University | Larsson B.,Linköping University | Forsberg F.,Linköping University | Ghafouri N.,Linköping University | And 4 more authors.
Clinical Journal of Pain | Year: 2014

BACKGROUND: Chronic widespread pain (CWP), including fibromyalgia syndrome (FM), is associated with prominent negative consequences. CWP has been associated with alterations in the central processing of nociception. Whereas some researchers consider CWP/FM as a central hyperexcitability pain condition, others suggest that the central alterations are maintained by peripheral nociceptive input. Microdialysis can be used in vivo to study muscle alterations in chronic myalgia. AIM: The aim of the study was to investigate the plasma and interstitial concentrations of metabolites and algesics in the trapezius muscle of women with CWP and in pain-free women (CON). MATERIALS AND METHODS: Seventeen women with CWP and 24 CON went through a clinical examination and completed a questionnaire; the pressure pain thresholds in the upper and lower extremities were registered. Microdialysis was conducted in the trapezius muscle, and a blood sample was drawn. Muscle blood flow, interstitial muscle concentrations, and plasma concentrations of lactate, pyruvate, glutamate, glucose, and glycerol (not in the plasma) were determined. RESULTS: CWP patients had significantly increased interstitial muscle (P=0.02 to 0.001) and plasma (P=0.026 to 0.017) concentrations of lactate and glutamate. No significant differences existed in blood flow between CWP and CON. The interstitial concentrations - but not the plasma levels - of glutamate and lactate correlated significantly with aspects of pain such as pressure pain thresholds of the trapezius (R=0.22) and tibialis anterior (R=0.18) and the mean pain intensity (R=0.10) in CWP but not in CON. CONCLUSIONS: The present study supports the suggestion that aspects of pain and central alterations in CWP/FM are influenced by peripheral tissue alterations. Copyright © 2013 by Lippincott Williams & Wilkins.


Ghafouri N.,Linköping University | Ghafouri N.,Pain and Rehabilitation Center | Ghafouri N.,Umeå University | Ghafouri B.,Linköping University | And 8 more authors.
Pain | Year: 2013

Chronic widespread pain (CWP) is a complex condition characterized by central hyperexcitability and altered descending control of nociception. However, nociceptive input from deep tissues is suggested to be an important drive. N-Acylethanolamines (NAEs) are endogenous lipid mediators involved in regulation of inflammation and pain. Previously we have reported elevated levels of the 2 NAEs, the peroxisome proliferator-activated receptor type-α ligand N-palmitoylethanolamine (PEA) and N-stearoylethanolamine (SEA) in chronic neck/shoulder pain (CNSP). In the present study, the levels of PEA and SEA in women with CWP (n = 18), CNSP (n = 34) and healthy controls (CON, n = 24) were investigated. All subjects went through clinical examination, pressure pain threshold measurements and induction of experimental pain in the tibialis anterior muscle. Microdialysis dialysate of the trapezius was collected before and after subjects performed a repetitive low-force exercise and analyzed by mass spectrometry. The levels of PEA and SEA in CNSP were significantly higher post exercise compared with CWP, and both pre and post exercise compared with CON. Levels of both NAEs decreased significantly pre to post exercise in CWP. Intercorrelations existed between aspects of pain intensity and sensitivity and the level of the 2 NAEs in CWP and CNSP. This is the first study demonstrating that CNSP and CWP differ in levels of NAEs in response to a low-force exercise which induces pain. Increases in pain intensity as a consequence of low-force exercise were associated with low levels of PEA and SEA in CNSP and CWP. These results indicate that PEA and SEA have antinociceptive roles in humans. © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.


Borsbo B.,Linköping University | Borsbo B.,County Hospital Ryhov | Liedberg G.M.,Linköping University | Wallin M.,Linköping University | And 2 more authors.
Journal of Pain Research | Year: 2012

Purpose: To investigate the presence of subgroups in chronic whiplash-associated disorders (WAD) based on pain thresholds for pressure (PPT), cold (CPT), and heat (HPT) and to compare these subgroups with respect to symptomatology, disability, and health aspects. Methods: Two groups of female subjects - patients with chronic WAD (n  =   28) and healthy controls (CON; n  = 29) - were investigated. Quantitative sensory testing (QST) for thermal thresholds and algometry for PPT at four sites in the body (over the trapezius and tibialis anterior bilaterally) were determined. Habitual pain intensities, psychological strain, disability, and health aspects were registered using a questionnaire. Results: A cluster analysis based on PPT, CPT, and HPT identified two subgroups of chronic WAD: one sensitive subgroup (s-WAD; n = 21), and one less sensitive subgroup (ls-WAD; n  = 6). S-WAD displayed widespread hyperalgesia, whereas ls-WAD had localized hyperalgesia in the neck area, with tendencies to supernormal values in remote areas of the body. Generally, s-WAD had a significantly worse situation than the CON with respect to symptomatology, disability, and health aspects. The ls-WAD group was intermediary between s-WAD and CON in these aspects. Conclusion: Different explanations, eg, severity of the pain condition per se, etiological factors, and pre-trauma differences in pain sensitivity, may exist for the differences in pain thresholds between the two subgroups. Future research should investigate the role of pain thresholds in the chronic stage to determine the efficacy of treatment interventions. © 2012 Börsbo et al publisher and licensee Dove Medical Press Ltd.


Backryd E.,Linköping University | Backryd E.,Pain and Rehabilitation Center | Ghafouri B.,Linköping University | Ghafouri B.,Pain and Rehabilitation Center | And 4 more authors.
Pain Medicine (United States) | Year: 2014

Objective: Pain medicine still lacks mechanism-specific biomarkers to guide diagnosis and treatment, and defective top-down modulation is an important factor in the pathophysiology of chronic pain conditions. Using modern analytical tools and advanced multivariate statistical analysis, the aim of this study was to revisit two classical potential biomarkers of pro- and anti-nociception in humans (substance P and beta-endorphin), focusing particularly on the cerebrospinal fluid (CSF). Design: Cross-sectional, comparative, observational study. Subjects: Patients with chronic, post-traumatic and/or post-surgical, neuropathic pain refractory to conventional treatment (N=15) and healthy controls (N=19) were included. Methods: Samples were taken from CSF and blood, and levels of substance P and beta-endorphin were investigated using a Luminex technology kit. Results: We found low levels of beta-endorphin in the CSF of neuropathic pain patients (66±11pcg/mL) compared with healthy controls (115±14pcg/mL) (P=0.017). Substance P levels in the CSF did not differ (20±2pcg/mL, 26±2, P=0.08). However, our multivariate data analysis showed that belonging to the patient group was associated with low levels of both substances in the CSF. A higher correlation between the levels of beta-endorphin and substance P in CSF was found in healthy controls than in patients (rs=0.725, P<0.001 vs rs=0.574, P=0.032). Conclusions: Patients with chronic neuropathic pain due to trauma or surgery had low levels of beta-endorphin in the CSF. We speculate that this could indicate a defective top-down modulation of pain in chronic neuropathic pain. Our results also illustrate the importance of taking a system-wide, multivariate approach when searching for biomarkers. © 2014 Original Research Article Wiley Periodicals, Inc.


Alfoldi P.,Linköping University | Alfoldi P.,Pain and Rehabilitation Center | Wiklund T.,Linköping University | Wiklund T.,Pain and Rehabilitation Center | And 2 more authors.
Disability and Rehabilitation | Year: 2014

Purpose: This study investigates the prevalence of insomnia and its relationship to other symptoms and health aspects in patients with chronic pain. Methods: Patients with chronic pain conditions (n=845) referred to a multidisciplinary pain centre completed surveys provided by the Swedish quality registry for pain rehabilitation (SQRP). The SQRP collects data on socio-demographics, health status, symptoms of pain, mood and insomnia and life satisfaction. Results: The majority of patients (65.3%) had clinical insomnia according to the insomnia severity index (ISI). Insomnia correlated significantly but weakly with pain, depression, anxiety and coping; the strongest multivariate correlations were found with depression and anxiety followed by pain interference and pain severity. Pain intensity, depression and anxiety correlated stronger than ISI with respect to the two investigated aspects of health. Conclusions: The prevalence of insomnia is high in patients with chronic pain conditions, but the level of importance in relation to other symptoms for health aspects is low, and the associations with other important symptoms are relatively weak. One way to increase the effects of multimodal rehabilitation programs may be to provide interventions directed specifically at insomnia rather than focusing only on interventions that address pain, depression and anxiety.Implications for RehabilitationThe prevalence of insomnia is high in patients with complex chronic pain conditions.Relatively low correlations existed between insomnia and pain intensity, depression, anxiety and other psychological aspects.Pain intensity, anxiety and depression were more important for perceived health aspects than insomnia.One way to increase the effects of multimodal rehabilitation programs may be to also include interventions directed directly to insomnia. © 2014 Informa UK Ltd. All rights reserved.


Gerdle B.,Linköping University | Gerdle B.,Pain and Rehabilitation Center | Ghafouri B.,Linköping University | Ernberg M.,Karolinska Institutet | And 2 more authors.
Journal of Pain Research | Year: 2014

Chronic musculoskeletal pain conditions are multifaceted, and approximately 20% of the adult population lives with severe chronic pain, with a higher prevalence in women and in lower income groups. Chronic pain is infuenced by and interacts with physical, emotional, psychological, and social factors, and a biopsychosocial framework is increasingly applied in clinical practice. However, there is still a lack of assessment procedures based on the activated neurobiological pain mechanisms (ie, the biological part of the biopsychosocial model of pain), which may be a necessary step for further optimizing outcomes after treatments for patients with chronic pain. It has been suggested that chronic pain conditions are mainly driven by alterations in the central nervous system with little or no peripheral stimuli or nociception. In contrast, other authors argue that such central alterations are driven by peripheral alterations and nociceptive input. Microdialysis is an in vivo method for studying local tissue alterations and allows for sampling of substances in the interstitium of the muscle, where nociceptor free nerve endings are found close to the muscle fibers. The extracellular matrix plays a key role in physiologic functions of cells, including the primary afferent nociceptor. The present review mainly concerns the results of microdialysis studies and how they can contribute to the understanding of activated peripheral nociceptive and pain mechanisms in humans with chronic pain. The primary aim was to review molecular studies using microdialysis for the investigation of human chronic muscle pain, ie, chronic masticatory muscle pain, chronic trapezius myalgia, chronic whiplash-associated disorders, and chronic widespread pain/fbromyalgia syndrome. Several studies clearly showed elevated levels of serotonin, glutamate, lactate, and pyruvate in localized chronic myalgias and may be potential biomarkers. These results indicate that peripheral muscle alterations are parts of the activated pain mechanisms in common chronic pain conditions. Muscle alterations have been reported in fbromyalgia syndrome and chronic widespread pain, but more studies are needed before definite conclusions can be drawn. For other substances, results are inconclusive across studies and patient groups. © 2014 Gerdle et al.


PubMed | Karolinska Institutet, Pain and Rehabilitation Center and Linköping University
Type: | Journal: Neuroscience letters | Year: 2016

Peripheral nerve injuries result in reorganization within the contralateral hemisphere. Furthermore, recent animal and human studies have suggested that the plastic changes in response to peripheral nerve injury also include several areas of the ipsilateral hemisphere. The objective of this study was to map the inter-hemispheric plasticity in response to median nerve injury, to investigate normal differences in contra- and ipsilateral activation, and to study the impact of event-related or blocked functional magnetic resonance imaging (fMRI) design on ipsilateral activation. Four patients with median nerve injury at the wrist (injured and epineurally sutured >2 years earlier) and ten healthy volunteers were included. 3T fMRI was used to map the hemodynamic response to brain activity during tactile stimulation of the fingers, and a laterality index (LI) was calculated. Stimulation of Digits II-III of the injured hand resulted in a reduction in contralateral activation in the somatosensory area SI. Patients had a lower LI (0.210.15) compared to healthy controls (0.600.26) indicating greater ipsilateral activation of the primary somatosensory cortex. The spatial dispersion of the coordinates for areas SI and SII was larger in the ipsilateral than in the contralateral hemisphere in the healthy controls, and was increased in the contralateral hemisphere of the patients compared to the healthy controls. There was no difference in LI between the event-related and blocked paradigms. In conclusion, patients with median nerve injury have increased ipsilateral SI area activation, and spatially more dispersed contralateral SI activation during tactile stimulation of their injured hand. In normal subjects ipsilateral activation has larger spatial distribution than the contralateral. Previous findings in patients performed with the blocked fMRI paradigm were confirmed. The increase in ipsilateral SI activation may be due to an interhemispheric disinhibition associated with changes in the afferent signal inflow to the contralateral primary somatosensory cortex.


Hamza M.,Virginia Commonwealth University | Doleys D.,Pain and Rehabilitation Center | Wells M.,Sheltering Arms Rehabiliation Center | Weisbein J.,Virginia Commonwealth University | And 6 more authors.
Pain Medicine (United States) | Year: 2012

Objective. Long-term follow-up with the use of low-dose opioids in intrathecal (IT) drug delivery system (DDS) for the treatment of intractable, severe chronic nonmalignant pain. Design. This is a prospective, cohort long-term outcome study. Intervention. The intervention was the implantation of DDS. Method and patients. A total of 61 consecutive patients (60% females, 40% males) with a mean age of 59.2 years and a mean duration of symptoms prior to implant of 6.2 years were referred for implant of DDS for severe intractable noncancer pain. After adequate patient evaluation, each underwent a trial with IT opioids. Three patients failed the trial and 58 patients were implanted. Follow-up was 36 months, with intervals at 6, 12, 18, 24, and 36 months. The Brief Pain Inventory was used for follow-up assessment criteria at baseline prior to implant as well as throughout the duration of the study. Outcome Measures. Outcome measures included self-reported pain scores (worst and average), functional improvement, and IT dose, and oral opioid consumption. Results. We observed a statistically significant reduction in both worst and average pain from baseline (8.91 and 7.47 at baseline) throughout the duration of the study (4.02 and 3.41, respectively, at 36 months) (P=0.012 and P<0.001, respectively). We also documented a statistically significant improvement in physical and behavioral function. All subjects showed a significant reduction in the oral opioid consumption. The dose of IT opioids remained low and virtually unchanged for 36 months of follow-up: 1.4 morphine equivalent/day at 6 months and 1.48 at 36 months. Oral opioid averaged 128.9mg of morphine equivalent/patient/day at baseline to 3.8 at 3 month and remained at the same level throughout the study. Conclusion. Low-dose IT opioid can provide sustained significant improvement in pain and function for long-term follow-up in chronic noncancer pain. © 2012 Wiley Periodicals, Inc.

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