Torsten Gordh - Academia.edu (original) (raw)
Papers by Torsten Gordh
Pain, 2019
Two recent studies suggest that experimental pain sensitivity is associated with low-grade system... more Two recent studies suggest that experimental pain sensitivity is associated with low-grade systemic inflammation. However, only 2 biomarkers have been identified, and the studies were conducted in adult individuals where confounding effects of comorbid diseases cannot be excluded. We therefore tested associations between pain sensitivity and 119 inflammation-related serum biomarkers in 827 healthy adolescents (15-19 years) in the population-based Tromsø Study: Fit Futures. The main outcome measure was cold-pressor pain tolerance (CPT), tested by placing the dominant hand in circulating cold (3°C) water for a maximum of 105 seconds. Secondary outcomes were heat and pressure pain threshold and tolerance. Twelve proteins and 6 fatty acids were significantly associated with CPT after adjustment for possible confounding factors and correction for multiple comparisons. Of these, all fatty acids and 10 proteins were protective, ie, higher biomarkers levels were associated with increased CP...
Acta Anaesthesiologica Scandinavica, 2014
During recent decades, the increasing use of opioids for chronic non‐cancer pain has raised conce... more During recent decades, the increasing use of opioids for chronic non‐cancer pain has raised concerns regarding tolerance, addiction, and importantly cognitive dysfunction. Current research suggests that the somatotrophic axis could play an important role in cognitive function. Administration of growth hormone (GH) to GH‐deficient humans and experimental animals has been shown to result in significant improvements in cognitive capacity. In this report, a patient with cognitive disabilities resulting from chronic treatment with opioids for neuropathic pain received recombinant human growth hormone (rhGH) replacement therapy. A 61‐year‐old man presented with severe cognitive dysfunction after long‐term methadone treatment for intercostal neuralgia and was diagnosed with GH insufficiency by GH releasing hormone‐arginine testing. The effect of rhGH replacement therapy on his cognitive capacity and quality of life was investigated. The hippocampal volume was measured using magnetic resona...
Disability and Rehabilitation, May 16, 2023
Journal of Applied Toxicology, 2017
Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic... more Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected. Mice of both sexes were exposed to two doses of paracetamol (30 + 30 mg kg-1 , 4 h apart) on postnatal days (PND) 3, 10 or 19. Spontaneous behavior, when introduced to a new home environment, was observed at the age of 2 months. We show that adverse effects on adult behavior and cognitive function occurred in both male and female mice exposed to paracetamol on PND 3 and 10, but not when exposed on PND 19. These neurodevelopmental time points in mice correspond to the beginning of the third trimester of pregnancy and the time around birth in humans, supporting existing human data. Considering that paracetamol is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for future research and, ultimately, for clinical practice.
Purpose: Positron emission tomography with the radioligand [11C]D-deprenyl has shown an increased... more Purpose: Positron emission tomography with the radioligand [11C]D-deprenyl has shown an increased signal at the location of pain in patients with ankle sprains, rheumatoid arthritis and chronic whi ...
Biomedicines
Trigeminal neuralgia (TN) is a severe type of facial pain. A neurovascular conflict between crani... more Trigeminal neuralgia (TN) is a severe type of facial pain. A neurovascular conflict between cranial nerve V and a nearby vessel is the main pathophysiological mechanism, but additional factors are likely necessary to elicit TN. In this study, the primary aim was to explore differences in protein expression in the cerebrospinal fluid (CSF) of TN patients in relation to controls. Methods: Sixteen TN patients treated with microvascular decompression and 16 control patients undergoing spinal anesthesia for urological conditions were included. Lumbar CSF was collected preoperatively for the TN patients and before spinal anesthesia for the controls. A multiplexed proximity extension analysis of 91 CSF proteins was conducted using Proseek Multiplex Development 96, including biomarkers of cell communication, cell death, neurogenesis, and inflammation Results: The TN patients and the controls were of similar age, sex, and burden of co-morbidities. The TN patients exhibited higher concentrati...
The Journal of Pain
The main cause of trigeminal neuralgia (TN) is compression of a blood vessel at the root entry zo... more The main cause of trigeminal neuralgia (TN) is compression of a blood vessel at the root entry zone of the trigeminal nerve. However, a neurovascular conflict does not seem to be the only etiology and other mechanisms are implicated in the development of the disease. We hypothesized that TN patients may have distinct protein expression in the CSF. In this study, lumbar CSF from TN patients (n=17), scheduled to undergo microvascular decompression (MVD), and from controls (n=20) was analyzed and compared with mass spectrometry-based shotgun proteomics. 2552 unique proteins were identified of which 46 were significantly altered (26 increased, and 20 decreased, q-value < 0.05) in TN patients compared with controls. An over-representation analysis showed proteins involved in high-density lipoprotein (HDL), such as APOA-4, APOM and APOA-1, and the extracellular region, including proteins involved in the complement cascade to be over-represented. We conclude that TN patients have distinct protein expression in the CSF compared to controls. The pathophysiological background of the protein alterations found in this study warrants further investigation in future studies. Perspective: In this article, cerebrospinal fluid from patients with trigeminal neuralgia was analyzed using in depth shotgun proteomics, revealing 46 differentially expressed proteins compared to controls. Among these, apolipoproteins and proteins involved in the complement system were elevated and significantly over-represented, implying an inflammatory component in the pathophysiology of the disease.
Scandinavian Journal of Pain, 2019
Background and aims Aside from the long term side effects of a nerve injury in the upper extremit... more Background and aims Aside from the long term side effects of a nerve injury in the upper extremity with devastating consequences there is often the problem of chronic neuropathic pain. The studies concerning the prevalence of persistent pain of neuropathic origin after peripheral nerve injuries are sparse. The prevalence and risk factors associated with chronic neuropathic pain after nerve injuries in the upper extremity were assessed. Methods A standardized data collection template was employed prospectively and retrospectively for all patients with traumatic nerve injuries accepted at the Hand Surgery Department, Uppsala, Sweden between 2010 and 2018. The template included demographic data, pain diagnosis, type of injured nerve, level of injury, date of the lesion and repair, type of procedure, reoperation, time since the procedure, S-LANSS questionnaire (Self report-Leeds Assessment of Neuropathic Symptoms and Signs), RAND-36 (Item short form health survey), QuickDASH (Disability...
Scandinavian Journal of Pain, 2017
Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pai... more Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pain patients (CPP) [1, 2]. In the present study we investigated the plasma inflammatory profile in severely impaired chronic pain patients. In addition we studied if there were any alterations in inflammation patterns at one-year follow up, after the patients had taken part in a CBT-ACT based 4 weeks in-hospital pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well characterized chronic pain patients. Plasma from matched healthy blood donors were used as controls. At one year after the treatment program, 28 of the patients were available for follow up. Instead of only analyzing single inflammation-related substances, we used a new multiplex panel enabling the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines (Proseek Inflammation, Olink, Uppsala, Sweden). Multivariate statistics were used for analysis. Results Clear si...
Behavioral Sleep Medicine, 2015
Cognitive behavioral therapy produces significant and long-lasting improvement for individuals wi... more Cognitive behavioral therapy produces significant and long-lasting improvement for individuals with insomnia, but treatment resources are scarce. A &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;stepped care&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; approach has therefore been proposed, but knowledge is limited on how to best allocate patients to different treatment steps. In this study, 66 primary-care patients with insomnia attended a low-end treatment step: manual-guided cognitive behavioral therapy (CBT) for insomnia delivered by ordinary primary-care personnel. Based on clinically significant treatment effects, subjects were grouped into treatment responders or nonresponders. Baseline data were analyzed to identify predictors for treatment success. Long total sleep time at baseline assessment was the only statistically significant predictor for becoming a responder, and sleep time may thus be important to consider before enrolling patients in low-end treatments.
Scandinavian Journal of Pain, 2012
Background/aims An objective correlate of ongoing painful process in peripheral tissue would repr... more Background/aims An objective correlate of ongoing painful process in peripheral tissue would represent a progress in the analysis of pain. The aim of this study was to investigate if the extent of the injury and inflammation in musculoskeletal injuries can be visualized, quantified and followed over time using positron emission tomography (PET) with the radioligand [11C]-D-deprenyl. Methods Eight otherwise healthy patients with unilateral ankle sprain were PET-imaged acutely and followed up twice, first a month and then up to over one year after injury. Results Acutely [11C]-D-deprenyl uptake was significantly increased by a factor 10.7 (range 2.9–37.3) in the injury sites as compared to the intact ankle. During healing [11C]-D-deprenyl uptake was reduced, but not normalized until after 11 months. Conclusions Patients experiencing persistent pain showed prolonged [11C]-D-deprenyl uptake in the injury sites. Thus, PET can be used to visualize, quantify and follow painful processes in...
![Research paper thumbnail of Elevated [11C]-D-Deprenyl Uptake in Chronic Whiplash Associated Disorder Suggests Persistent Musculoskeletal Inflammation](https://attachments.academia-assets.com/87019582/thumbnails/1.jpg)
](PLoS ONE, 2011
There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods sel... more There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer 11 C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II) and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that 11 C-D-deprenyl is a promising tracer for these purposes.
Pain, 2010
Neurokinin 1 (NK1) receptors are involved in pain and anxiety behaviors in animals, but little is... more Neurokinin 1 (NK1) receptors are involved in pain and anxiety behaviors in animals, but little is known about central alterations in this receptor system in human pain. With positron emission tomography, using a [11]-Carbon labeled NK1 receptor antagonist, we demonstrate attenuated NK1 receptor availability in frontal, insular and cingulate cortex, as well as the hippocampus, amygdala and the periaqueductal gray area in patients with chronic pain. The reduced availability was most pronounced in the ventromedial prefrontal cortex (vmPFC), where attenuations correlated to measures of fear and avoidance of movement. Further, vmPFC NK1 levels also displayed opposing influences in patients as compared to controls on regional cerebral blood flow in the anterior cingulate. We conclude that the central NK1 receptor system is altered in human chronic pain. The results suggest that NK1 receptors in the vmPFC modulate motor inhibition, and contribute to fear and avoidance of movement.
Journal of Neural Transmission, 2006
The possibility that oxidative stress participates in heat shock protein 72 kD (HSP 72) expressio... more The possibility that oxidative stress participates in heat shock protein 72 kD (HSP 72) expression following a focal trauma to the spinal cord was examined using a potent antioxidant compound H-290=51 in a rat model. A focal spinal cord injury (SCI) inflicted by making a longitudinal incision on the right dorsal horn of the T10-T11 segment under equithesin anaesthesia resulted in profound upregulation of HSP 72 expression in the adjacent spinal cord segments T9 and T12. This expression of HSP was most marked in the ipsilateral cord at 5 h after SCI. Pretreatment with H-290=51 (50 mg=kg, p.o.) 30 min before SCI markedly attenuated HSP expression in the spinal cord seen at 5 h. The motor functions of traumatized rats were also improved in the drug treated group. At this time, structural changes in the spinal cord and edema formation were considerable reduced compared to the untreated traumatized rats. Taken together, these observations suggest that (i) oxidative stress participates in HSP response following trauma, and (ii) the antiox-idant compound H-290=51 attenuates cellular stress, improves motor functions and induces considerable neuroprotection in the early phase of SCI. Further studies using postinjury treatment with H-290=51 is needed to explore its therapeutic potentials in clinical settings.
Anesthesiology, 2010
Before the introduction of lidocaine, the choice of local anesthetics was limited. Procaine was m... more Before the introduction of lidocaine, the choice of local anesthetics was limited. Procaine was most commonly used and offered less toxicity than cocaine, but it had a short duration of action. Tetracaine had substantial systemic toxicity, limiting its use largely to spinal anesthesia. An agent with low toxicity, a quick onset, and a longer duration of action was needed. This article reports the initial clinical trials with the newly synthesized lidocaine. The first trials were wheal tests on the forearms of human volunteers. Lidocaine anesthesia duration was markedly longer than that produced by procaine. Lidocaine was first tested for infiltration anesthesia in many short procedures performed in the emergency department, followed by major procedures, including those for goiter and hernia in the operating room. Consistent success was observed in both environments. Lidocaine was then tested for conduction anesthesia using brachial plexus and mandibular, sacral, and paravertebral blocks. Its onset was again substantially faster and longer lasting than that of procaine. Lidocaine also provided good spinal and surface anesthesia of the cornea. T HIS article is based mainly on an interview with Torsten
Chronic inflammation in whiplash patients: Evidence from [11C]D-deprenyl Positron Emission Tomogr... more Chronic inflammation in whiplash patients: Evidence from [11C]D-deprenyl Positron Emission Tomography
PLoS ONE, 2013
In response to pain, neurokinin 1 (NK1) receptor availability is altered in the central nervous s... more In response to pain, neurokinin 1 (NK1) receptor availability is altered in the central nervous system. The NK1 receptor and its primary agonist, substance P, also play a crucial role in peripheral tissue in response to pain, as part of neurogenic inflammation. However, little is known about alterations in NK1 receptor availability in peripheral tissue in chronic pain conditions and very few studies have been performed on human beings. Ten subjects with chronic tennis elbow were therefore examined by positron emission tomography (PET) with the NK1 specific radioligand [ 11 C]GR205171 before and after treatment with graded exercise. The radioligand signal intensity was higher in the affected arm as compared with the unaffected arm, measured as differences between the arms in volume of voxels and signal intensity of this volume above a reference threshold set as 2.5 SD above mean signal intensity of the unaffected arm before treatment. In the eight subjects examined after treatment, pain ratings decreased in all subjects but signal intensity decreased in five and increased in three. In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings. The increased NK1 receptor availability is interpreted as part of ongoing neurogenic inflammation and may have correlation to the pathogenesis of chronic tennis elbow.
European Journal of Pain, 2009
The neural pathogenic mechanisms involved in mediating chronic pain and whiplash associated disor... more The neural pathogenic mechanisms involved in mediating chronic pain and whiplash associated disorders (WAD) after rear impact car collisions are largely unknown. This study&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s first objective was to compare resting state regional cerebral blood flow (rCBF) by means of positron emission tomography with (15)O labelled water in 21 WAD patients with 18 healthy, pain-free controls. A second objective was to investigate the relations between brain areas with altered rCBF to pain experience, somatic symptoms, posttraumatic stress symptoms and personality traits in the patient group. Patients had heightened resting rCBF bilaterally in the posterior parahippocampal and the posterior cingulate gyri, in the right thalamus and the right medial prefrontal gyrus as well as lowered tempero-occipital blood flow compared with healthy controls. The altered rCBF in the patient group was correlated to neck disability ratings. We thus suggest an involvement of the posterior cingulate, parahippocampal and medial prefrontal gyri in WAD and speculate that alterations in the resting state are linked to an increased self-relevant evaluation of pain and stress.
PAIN Reports
Introduction and Objectives: We previously found that women report more pain after knee arthrosco... more Introduction and Objectives: We previously found that women report more pain after knee arthroscopic procedures than men. It remains unclear whether this is due to different biochemical responses or nociceptive mechanisms. Methods: We analyzed acute pain-related inflammatory markers in a clinical model of patient self-reported pain immediately after knee surgery. To simultaneously measure 92 inflammatory biomarkers, we used the proximity extension assay with the Proseek Multiplex Inflammation I panel (Olink Bioscience, Uppsala, Sweden). Knee surgery was performed under general anesthesia with propofol and remifentanil. Analgesic drugs were only administered on patient request. Results: Women were 4.9 times more likely to report moderate or severe pain than men (95% confidence interval, 1.2-19.6, P 5 0.024). Patient age, preoperative pain, and surgery duration were not significant factors. We analyzed synovial fluids from 44 patients (23 women, 21 men). After false discovery rate correction, MMP-10 was the only biomarker that was higher among men (P 5 0.01). Linear discriminant analysis showed that 3 proteins (IL-8, CCL-4, and MCP-2) were expressed at higher levels in men, with differences of .1 normalized protein expression. No proteins were overexpressed by .1 normalized protein expression in women. Conclusion: Acute pain after knee arthroscopy was more intense in women, but pro-inflammatory biomarkers and MMP-10 were higher in men. Further knowledge of cytokine function is required before concluding that the disparities in biomarker expression are clinically unimportant. The similar biochemical signaling between sexes suggests that central mechanisms are of greater importance in sex-specific joint pain perception.
Pain, 2019
Two recent studies suggest that experimental pain sensitivity is associated with low-grade system... more Two recent studies suggest that experimental pain sensitivity is associated with low-grade systemic inflammation. However, only 2 biomarkers have been identified, and the studies were conducted in adult individuals where confounding effects of comorbid diseases cannot be excluded. We therefore tested associations between pain sensitivity and 119 inflammation-related serum biomarkers in 827 healthy adolescents (15-19 years) in the population-based Tromsø Study: Fit Futures. The main outcome measure was cold-pressor pain tolerance (CPT), tested by placing the dominant hand in circulating cold (3°C) water for a maximum of 105 seconds. Secondary outcomes were heat and pressure pain threshold and tolerance. Twelve proteins and 6 fatty acids were significantly associated with CPT after adjustment for possible confounding factors and correction for multiple comparisons. Of these, all fatty acids and 10 proteins were protective, ie, higher biomarkers levels were associated with increased CP...
Acta Anaesthesiologica Scandinavica, 2014
During recent decades, the increasing use of opioids for chronic non‐cancer pain has raised conce... more During recent decades, the increasing use of opioids for chronic non‐cancer pain has raised concerns regarding tolerance, addiction, and importantly cognitive dysfunction. Current research suggests that the somatotrophic axis could play an important role in cognitive function. Administration of growth hormone (GH) to GH‐deficient humans and experimental animals has been shown to result in significant improvements in cognitive capacity. In this report, a patient with cognitive disabilities resulting from chronic treatment with opioids for neuropathic pain received recombinant human growth hormone (rhGH) replacement therapy. A 61‐year‐old man presented with severe cognitive dysfunction after long‐term methadone treatment for intercostal neuralgia and was diagnosed with GH insufficiency by GH releasing hormone‐arginine testing. The effect of rhGH replacement therapy on his cognitive capacity and quality of life was investigated. The hippocampal volume was measured using magnetic resona...
Disability and Rehabilitation, May 16, 2023
Journal of Applied Toxicology, 2017
Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic... more Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected. Mice of both sexes were exposed to two doses of paracetamol (30 + 30 mg kg-1 , 4 h apart) on postnatal days (PND) 3, 10 or 19. Spontaneous behavior, when introduced to a new home environment, was observed at the age of 2 months. We show that adverse effects on adult behavior and cognitive function occurred in both male and female mice exposed to paracetamol on PND 3 and 10, but not when exposed on PND 19. These neurodevelopmental time points in mice correspond to the beginning of the third trimester of pregnancy and the time around birth in humans, supporting existing human data. Considering that paracetamol is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for future research and, ultimately, for clinical practice.
Purpose: Positron emission tomography with the radioligand [11C]D-deprenyl has shown an increased... more Purpose: Positron emission tomography with the radioligand [11C]D-deprenyl has shown an increased signal at the location of pain in patients with ankle sprains, rheumatoid arthritis and chronic whi ...
Biomedicines
Trigeminal neuralgia (TN) is a severe type of facial pain. A neurovascular conflict between crani... more Trigeminal neuralgia (TN) is a severe type of facial pain. A neurovascular conflict between cranial nerve V and a nearby vessel is the main pathophysiological mechanism, but additional factors are likely necessary to elicit TN. In this study, the primary aim was to explore differences in protein expression in the cerebrospinal fluid (CSF) of TN patients in relation to controls. Methods: Sixteen TN patients treated with microvascular decompression and 16 control patients undergoing spinal anesthesia for urological conditions were included. Lumbar CSF was collected preoperatively for the TN patients and before spinal anesthesia for the controls. A multiplexed proximity extension analysis of 91 CSF proteins was conducted using Proseek Multiplex Development 96, including biomarkers of cell communication, cell death, neurogenesis, and inflammation Results: The TN patients and the controls were of similar age, sex, and burden of co-morbidities. The TN patients exhibited higher concentrati...
The Journal of Pain
The main cause of trigeminal neuralgia (TN) is compression of a blood vessel at the root entry zo... more The main cause of trigeminal neuralgia (TN) is compression of a blood vessel at the root entry zone of the trigeminal nerve. However, a neurovascular conflict does not seem to be the only etiology and other mechanisms are implicated in the development of the disease. We hypothesized that TN patients may have distinct protein expression in the CSF. In this study, lumbar CSF from TN patients (n=17), scheduled to undergo microvascular decompression (MVD), and from controls (n=20) was analyzed and compared with mass spectrometry-based shotgun proteomics. 2552 unique proteins were identified of which 46 were significantly altered (26 increased, and 20 decreased, q-value < 0.05) in TN patients compared with controls. An over-representation analysis showed proteins involved in high-density lipoprotein (HDL), such as APOA-4, APOM and APOA-1, and the extracellular region, including proteins involved in the complement cascade to be over-represented. We conclude that TN patients have distinct protein expression in the CSF compared to controls. The pathophysiological background of the protein alterations found in this study warrants further investigation in future studies. Perspective: In this article, cerebrospinal fluid from patients with trigeminal neuralgia was analyzed using in depth shotgun proteomics, revealing 46 differentially expressed proteins compared to controls. Among these, apolipoproteins and proteins involved in the complement system were elevated and significantly over-represented, implying an inflammatory component in the pathophysiology of the disease.
Scandinavian Journal of Pain, 2019
Background and aims Aside from the long term side effects of a nerve injury in the upper extremit... more Background and aims Aside from the long term side effects of a nerve injury in the upper extremity with devastating consequences there is often the problem of chronic neuropathic pain. The studies concerning the prevalence of persistent pain of neuropathic origin after peripheral nerve injuries are sparse. The prevalence and risk factors associated with chronic neuropathic pain after nerve injuries in the upper extremity were assessed. Methods A standardized data collection template was employed prospectively and retrospectively for all patients with traumatic nerve injuries accepted at the Hand Surgery Department, Uppsala, Sweden between 2010 and 2018. The template included demographic data, pain diagnosis, type of injured nerve, level of injury, date of the lesion and repair, type of procedure, reoperation, time since the procedure, S-LANSS questionnaire (Self report-Leeds Assessment of Neuropathic Symptoms and Signs), RAND-36 (Item short form health survey), QuickDASH (Disability...
Scandinavian Journal of Pain, 2017
Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pai... more Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pain patients (CPP) [1, 2]. In the present study we investigated the plasma inflammatory profile in severely impaired chronic pain patients. In addition we studied if there were any alterations in inflammation patterns at one-year follow up, after the patients had taken part in a CBT-ACT based 4 weeks in-hospital pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well characterized chronic pain patients. Plasma from matched healthy blood donors were used as controls. At one year after the treatment program, 28 of the patients were available for follow up. Instead of only analyzing single inflammation-related substances, we used a new multiplex panel enabling the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines (Proseek Inflammation, Olink, Uppsala, Sweden). Multivariate statistics were used for analysis. Results Clear si...
Behavioral Sleep Medicine, 2015
Cognitive behavioral therapy produces significant and long-lasting improvement for individuals wi... more Cognitive behavioral therapy produces significant and long-lasting improvement for individuals with insomnia, but treatment resources are scarce. A &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;stepped care&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; approach has therefore been proposed, but knowledge is limited on how to best allocate patients to different treatment steps. In this study, 66 primary-care patients with insomnia attended a low-end treatment step: manual-guided cognitive behavioral therapy (CBT) for insomnia delivered by ordinary primary-care personnel. Based on clinically significant treatment effects, subjects were grouped into treatment responders or nonresponders. Baseline data were analyzed to identify predictors for treatment success. Long total sleep time at baseline assessment was the only statistically significant predictor for becoming a responder, and sleep time may thus be important to consider before enrolling patients in low-end treatments.
Scandinavian Journal of Pain, 2012
Background/aims An objective correlate of ongoing painful process in peripheral tissue would repr... more Background/aims An objective correlate of ongoing painful process in peripheral tissue would represent a progress in the analysis of pain. The aim of this study was to investigate if the extent of the injury and inflammation in musculoskeletal injuries can be visualized, quantified and followed over time using positron emission tomography (PET) with the radioligand [11C]-D-deprenyl. Methods Eight otherwise healthy patients with unilateral ankle sprain were PET-imaged acutely and followed up twice, first a month and then up to over one year after injury. Results Acutely [11C]-D-deprenyl uptake was significantly increased by a factor 10.7 (range 2.9–37.3) in the injury sites as compared to the intact ankle. During healing [11C]-D-deprenyl uptake was reduced, but not normalized until after 11 months. Conclusions Patients experiencing persistent pain showed prolonged [11C]-D-deprenyl uptake in the injury sites. Thus, PET can be used to visualize, quantify and follow painful processes in...
PLoS ONE, 2011
There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods sel... more There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer 11 C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II) and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that 11 C-D-deprenyl is a promising tracer for these purposes.
Pain, 2010
Neurokinin 1 (NK1) receptors are involved in pain and anxiety behaviors in animals, but little is... more Neurokinin 1 (NK1) receptors are involved in pain and anxiety behaviors in animals, but little is known about central alterations in this receptor system in human pain. With positron emission tomography, using a [11]-Carbon labeled NK1 receptor antagonist, we demonstrate attenuated NK1 receptor availability in frontal, insular and cingulate cortex, as well as the hippocampus, amygdala and the periaqueductal gray area in patients with chronic pain. The reduced availability was most pronounced in the ventromedial prefrontal cortex (vmPFC), where attenuations correlated to measures of fear and avoidance of movement. Further, vmPFC NK1 levels also displayed opposing influences in patients as compared to controls on regional cerebral blood flow in the anterior cingulate. We conclude that the central NK1 receptor system is altered in human chronic pain. The results suggest that NK1 receptors in the vmPFC modulate motor inhibition, and contribute to fear and avoidance of movement.
Journal of Neural Transmission, 2006
The possibility that oxidative stress participates in heat shock protein 72 kD (HSP 72) expressio... more The possibility that oxidative stress participates in heat shock protein 72 kD (HSP 72) expression following a focal trauma to the spinal cord was examined using a potent antioxidant compound H-290=51 in a rat model. A focal spinal cord injury (SCI) inflicted by making a longitudinal incision on the right dorsal horn of the T10-T11 segment under equithesin anaesthesia resulted in profound upregulation of HSP 72 expression in the adjacent spinal cord segments T9 and T12. This expression of HSP was most marked in the ipsilateral cord at 5 h after SCI. Pretreatment with H-290=51 (50 mg=kg, p.o.) 30 min before SCI markedly attenuated HSP expression in the spinal cord seen at 5 h. The motor functions of traumatized rats were also improved in the drug treated group. At this time, structural changes in the spinal cord and edema formation were considerable reduced compared to the untreated traumatized rats. Taken together, these observations suggest that (i) oxidative stress participates in HSP response following trauma, and (ii) the antiox-idant compound H-290=51 attenuates cellular stress, improves motor functions and induces considerable neuroprotection in the early phase of SCI. Further studies using postinjury treatment with H-290=51 is needed to explore its therapeutic potentials in clinical settings.
Anesthesiology, 2010
Before the introduction of lidocaine, the choice of local anesthetics was limited. Procaine was m... more Before the introduction of lidocaine, the choice of local anesthetics was limited. Procaine was most commonly used and offered less toxicity than cocaine, but it had a short duration of action. Tetracaine had substantial systemic toxicity, limiting its use largely to spinal anesthesia. An agent with low toxicity, a quick onset, and a longer duration of action was needed. This article reports the initial clinical trials with the newly synthesized lidocaine. The first trials were wheal tests on the forearms of human volunteers. Lidocaine anesthesia duration was markedly longer than that produced by procaine. Lidocaine was first tested for infiltration anesthesia in many short procedures performed in the emergency department, followed by major procedures, including those for goiter and hernia in the operating room. Consistent success was observed in both environments. Lidocaine was then tested for conduction anesthesia using brachial plexus and mandibular, sacral, and paravertebral blocks. Its onset was again substantially faster and longer lasting than that of procaine. Lidocaine also provided good spinal and surface anesthesia of the cornea. T HIS article is based mainly on an interview with Torsten
Chronic inflammation in whiplash patients: Evidence from [11C]D-deprenyl Positron Emission Tomogr... more Chronic inflammation in whiplash patients: Evidence from [11C]D-deprenyl Positron Emission Tomography
PLoS ONE, 2013
In response to pain, neurokinin 1 (NK1) receptor availability is altered in the central nervous s... more In response to pain, neurokinin 1 (NK1) receptor availability is altered in the central nervous system. The NK1 receptor and its primary agonist, substance P, also play a crucial role in peripheral tissue in response to pain, as part of neurogenic inflammation. However, little is known about alterations in NK1 receptor availability in peripheral tissue in chronic pain conditions and very few studies have been performed on human beings. Ten subjects with chronic tennis elbow were therefore examined by positron emission tomography (PET) with the NK1 specific radioligand [ 11 C]GR205171 before and after treatment with graded exercise. The radioligand signal intensity was higher in the affected arm as compared with the unaffected arm, measured as differences between the arms in volume of voxels and signal intensity of this volume above a reference threshold set as 2.5 SD above mean signal intensity of the unaffected arm before treatment. In the eight subjects examined after treatment, pain ratings decreased in all subjects but signal intensity decreased in five and increased in three. In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings. The increased NK1 receptor availability is interpreted as part of ongoing neurogenic inflammation and may have correlation to the pathogenesis of chronic tennis elbow.
European Journal of Pain, 2009
The neural pathogenic mechanisms involved in mediating chronic pain and whiplash associated disor... more The neural pathogenic mechanisms involved in mediating chronic pain and whiplash associated disorders (WAD) after rear impact car collisions are largely unknown. This study&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s first objective was to compare resting state regional cerebral blood flow (rCBF) by means of positron emission tomography with (15)O labelled water in 21 WAD patients with 18 healthy, pain-free controls. A second objective was to investigate the relations between brain areas with altered rCBF to pain experience, somatic symptoms, posttraumatic stress symptoms and personality traits in the patient group. Patients had heightened resting rCBF bilaterally in the posterior parahippocampal and the posterior cingulate gyri, in the right thalamus and the right medial prefrontal gyrus as well as lowered tempero-occipital blood flow compared with healthy controls. The altered rCBF in the patient group was correlated to neck disability ratings. We thus suggest an involvement of the posterior cingulate, parahippocampal and medial prefrontal gyri in WAD and speculate that alterations in the resting state are linked to an increased self-relevant evaluation of pain and stress.
PAIN Reports
Introduction and Objectives: We previously found that women report more pain after knee arthrosco... more Introduction and Objectives: We previously found that women report more pain after knee arthroscopic procedures than men. It remains unclear whether this is due to different biochemical responses or nociceptive mechanisms. Methods: We analyzed acute pain-related inflammatory markers in a clinical model of patient self-reported pain immediately after knee surgery. To simultaneously measure 92 inflammatory biomarkers, we used the proximity extension assay with the Proseek Multiplex Inflammation I panel (Olink Bioscience, Uppsala, Sweden). Knee surgery was performed under general anesthesia with propofol and remifentanil. Analgesic drugs were only administered on patient request. Results: Women were 4.9 times more likely to report moderate or severe pain than men (95% confidence interval, 1.2-19.6, P 5 0.024). Patient age, preoperative pain, and surgery duration were not significant factors. We analyzed synovial fluids from 44 patients (23 women, 21 men). After false discovery rate correction, MMP-10 was the only biomarker that was higher among men (P 5 0.01). Linear discriminant analysis showed that 3 proteins (IL-8, CCL-4, and MCP-2) were expressed at higher levels in men, with differences of .1 normalized protein expression. No proteins were overexpressed by .1 normalized protein expression in women. Conclusion: Acute pain after knee arthroscopy was more intense in women, but pro-inflammatory biomarkers and MMP-10 were higher in men. Further knowledge of cytokine function is required before concluding that the disparities in biomarker expression are clinically unimportant. The similar biochemical signaling between sexes suggests that central mechanisms are of greater importance in sex-specific joint pain perception.