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  • 1.
    Biurrun Manresa, Jose A.
    et al.
    Aalborg University, Denmark.
    Sörensen, Jan
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Faculty of Medicine and Health Sciences.
    Andersen, Ole K.
    Aalborg University, Denmark.
    Arendt-Nielsen, Lars
    Aalborg University, Denmark.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Dynamic Changes in Nociception and Pain Perception After Spinal Cord Stimulation in Chronic Neuropathic Pain Patients2015In: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 31, no 12, p. 1046-1053Article in journal (Refereed)
    Abstract [en]

    Objectives: Patients with an implanted spinal cord stimulation (SCS) system for pain management present an opportunity to study dynamic changes in the pain system in a situation where patients are not stimulated (ie, experiencing severe pain) compared with a situation in which patients have just been stimulated (ie, pain free or greatly reduced pain). The aims of this study were (1) to determine if there are differences in nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) before and after SCS; and (2) to establish if these differences are related to psychological factors associated with chronic pain. Methods: Seventeen volunteers with chronic neuropathic pain participated in the experiment. Electrical stimuli were applied to assess the NWR-T and the EP-T. In addition, psychological factors (ie, pain characteristics, depression, anxiety, and disability indexes) were also recorded. The NWR-T and EP-T were assessed with the SCS system off (at least 8 h before the experiment), and then reassessed 1 hour after the SCS system was turned on. Results: Ongoing pain intensity ratings decreased (P=0.018), whereas the NWR-T increased (P=0.028) after the SCS was turned on, whereas no significant difference was found for EP-T (P=0.324). Psychological factors were significant predictors for EP-T but not for NWR-T. Discussion: The results of this study suggest that pain relief after SCS is partially mediated by a decrease in the excitability of dorsal horn neurons in the spinal cord.

  • 2.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Sörensen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Gerdle, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Nerve block as analgesia forneoplastic brachial plexopathy2010In: European Journal of Palliative Care, ISSN 1352-2779, E-ISSN 1479-0793, Vol. 17, no 5, p. 218-220Article in journal (Other academic)
    Abstract [en]

    Brachial plexus nerve blocks are performed to treat patients with chronic pain referable to the brachial plexus. The needle insertion and trajectory are based on palpation of surface landmarks. Occasionally, the surface landmarks are difficult to identify owing to body habitus or anatomic alterations secondary to surgery or radiation therapy. The intent of this manuscript is to describe a technique for brachial plexus block guided with computed tomography and to report our initial results for regional pain management.

  • 3.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Sörensen, Jan
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ziconotide Trialing by Intrathecal Bolus Injections: An Open-Label Non-Randomized Clinical Trial in Postoperative/Posttraumatic Neuropathic Pain Patients Refractory to Conventional Treatment2015In: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 18, no 5, p. 404-413Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this open-label, non-randomized, clinical trial was to evaluate the feasibility of trialing ziconotide by intrathecal bolus injections. Material and Methods: Twenty-three patients, who had peripheral neuropathic pain refractory to pharmacological treatment and were under consideration for Spinal Cord Stimulation, received up to three ziconotide bolus injections according to a comprehensive algorithm. After a first injection of 2.5g, the patients progressed in the algorithm depending on the presence or absence of pain reduction and significant adverse events. A patient was considered a "responder" if experiencing pain reduction and no significant adverse event on two consecutive occasions at the same dosage. Results: We found a low proportion of responders (13%). However 30% of patients experienced greater than= 30% pain reduction on a least one injection, yielding a number needed to treat of similar to 3 for clinically significant pain relief. Pain intensity changed significantly over time (0-6h) (p = 0.047) after a mean ziconotide dose of 2.75 mu g. Adverse events were as expected, and no serious adverse event occurred. We did not find any statistical association between response to Spinal Cord Stimulation and response to ziconotide. Conclusions: Ziconotide bolus injection trialing seems feasible, but the proportion of responders in the present study was low. Adverse events were as expected, and no serious adverse event occurred. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (slow tissue penetration due to high hydrophilicity) calls the rationale for bolus trialing into question.

  • 4.
    Gerdle, Björn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Sörensen, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Radiofrekvensbehandling2006In: Metoder för behandling av långvarig smärta: En systematisk litteraturöversikt / [ed] Statens beredning för medicinsk utvärdering, Stockholm: Statens beredning för medicinsk utvärdering (SBU) , 2006, p. 339-343Chapter in book (Other academic)
    Abstract [sv]

    I denna rapport sammanfattas det vetenskapliga underlaget för behandling av långvariga smärttillstånd. Smärta vid cancer innefattas inte. Smärtlindrande effekter, liksom biverkningar och andra negativa konsekvenser av behandling berörs samt hälsoekonomiska aspekter.

  • 5. Graven-Nielsen, T.
    et al.
    Sörensen, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Henriksson, Karl-Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Bengtsson, M.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Arendt-Nielsen, L.
    Central hyperexcitability in fibromyalgia1999In: Journal of Musculoskeletal Pain, ISSN 1058-2452, E-ISSN 1540-7012, Vol. 7, p. 261-267Article in journal (Refereed)
  • 6. Graven-Nilsen, T
    et al.
    Aspegren Kendall, Sally
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine/Pain Clinic. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Henriksson, Karl-Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine/Pain Clinic. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Bengtsson, M
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Sörensen, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Johnson, A
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Gerdle, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine/Pain Clinic. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Arendt-Nielsen, L
    Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients2000In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 85, no 3, p. 483-491Article in journal (Refereed)
    Abstract [en]

    Central mechanisms related to referred muscle pain and temporal summation of muscular nociceptive activity are facilitated in fibromyalgia syndrome (FMS) patients. The present study assessed the effects of an NMDA-antagonist (ketamine) on these central mechanisms. FMS patients received either i.v. placebo or ketamine (0.3 mg/kg, Ketalar(«)) given over 30 min on two separate occasions. Habitual pain intensity was assessed on a visual analogue scale (VAS). Initially, 29 FMS patients received ketamine or isotonic saline to determine which patients were ketamine responders (>50% decrease in pain intensity at rest by active drug on two consecutive VAS assessments). Fifteen out of 17 ketamine-responders were included in the second part of the study. Before and after ketamine or placebo, experimental local and referred pain was induced by intramuscular (i.m.) infusion of hypertonic saline (0.7 ml, 5%) into the tibialis anterior (TA) muscle. The saline-induced pain intensity was assessed on an electronic VAS, and the distribution of pain drawn by the subject. In addition, the pain threshold (PT) to i.m. electrical stimulation was determined for single stimulus and five repeated (2 Hz, temporal summation) stimuli. The pressure PT of the TA muscle was determined, and the pressure PT and pressure pain tolerance threshold were determined at three bilaterally located tenderpoints (knee, epicondyle, and mid upper trapezius). VAS scores of pain at rest were progressively reduced during ketamine infusion compared with placebo infusion. Pain intensity (area under the VAS curve) to the post-drug infusion of hypertonic saline was reduced by ketamine (-18.4▒0.3% of pre-drug VAS area) compared with placebo (29.9▒18.8%, P<0.02). Local and referred pain areas were reduced by ketamine (-12.0▒14.6% of pre-drug pain areas) compared with placebo (126.3▒83.2%, P<0.03). Ketamine had no significant effect on the PT to single i.m. electrical stimulation. However, the span between the PT to single and repeated i.m. stimuli was significantly decreased by the ketamine (-42.3▒15.0% of pre-drug PT) compared with placebo (50.5▒49.2%, P<0.03) indicating a predominant effect on temporal summation. Mean pressure pain tolerance from the three paired tenderpoints was increased by ketamine (16.6▒6.2% of pre-drug thresholds) compared with placebo (-2.3▒4.9%, P<0.009). The pressure PT at the TA muscle was increased after ketamine (42.4▒9.2% of pre-drug PT) compared with placebo (7.0▒6.6%, P<0.011). The present study showed that mechanisms involved in referred pain, temporal summation, muscular hyperalgesia, and muscle pain at rest were attenuated by the NMDA-antagonist in FMS patients. It suggested a link between central hyperexcitability and the mechanisms for facilitated referred pain and temporal summation in a sub-group of the fibromyalgia syndrome patients. Whether this is specific for FMS patients or a general phenomena in painful musculoskeletal disorders is not known. Copyright (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.

  • 7.
    Henriksson, Karl-Gösta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Sörensen, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    The promise of N-methyl-D-aspartate receptor antagonists in fibromyalgia2002In: Rheumatic Disease Clinics of North America, ISSN 0889-857X, E-ISSN 1558-3163, Vol. 28, no 2, p. 343-351Article in journal (Refereed)
    Abstract [en]

    There is strong evidence that intravenous administration of ketamine following a standardized protocol could be used as a diagnostic test for a central sensitization in the central nervous system in patients with FM. The combination of a weak opioid and an NMDA-receptor antagonist with few side effects is presently a promise for treatment of pain in a subgroup of patients with FM. The response to intravenously administered ketamine may help select patients for this treatment modality.

  • 8.
    Kalman, Sigga
    et al.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Österberg, Anders
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Sörensen, Jan
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Boivie, Jörgen
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Bertler, Åke
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Morphine responsiveness in a group of well-defined multiple sclerosis patients: a study with i.v. morphine2002In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 6, no 1, p. 69-80Article in journal (Refereed)
    Abstract [en]

    Pain in multiple sclerosis (MS) is more common than has previously been believed. About 28% of all MS patients suffer from central pain (CP), a pain that is difficult to treat. In the present study we have investigated the responsiveness of this pain to morphine. Fourteen opioid-free patients (eight woman and six men) with constant, non-fluctuating, long-lasting CP caused by MS were investigated. Placebo (normal saline), morphine and naloxone were given intravenously in a standardized manner. The study design was non-randomized, single blind and placebo controlled. Ten patients experienced less than 50% pain reduction by placebo and less than 50% pain reduction by morphine. Four patients were opioid responders, i.e. had minimal or no effect on pain by placebo, >50% pain reduction after morphine and >25% pain increase after naloxone, given intravenously following morphine. However, this response was obtained after high doses of morphine (43 mg, 47 mg, 50 mg and 25 mg; mean 41 mg). Thus, compared with nociceptive pain, only a minority of the patients with CP due to MS responded to morphine and only at high doses. The present results are in accord with experimental studies indicating that neuropathic pain is poorly responsive but not totally unresponsive to opioids. The results do not support the routine use of strong opioids in MS patients with CP.

  • 9.
    Kalso, Eija
    et al.
    Helsinki university, Finland.
    Allan, Laurie
    Northwick Park Hospital, Harrow, UK.
    Dobrogowski, Jan
    Medical college, Jagiellonian University, Krakow Poland.
    Johnson, Martin
    Ashville Medical Centre, Barnsley, UK.
    Krcevski-Skvarc, Nevenka
    Teaching Hospital, Maribor, Slovenia.
    Macfarlane, Gary J
    Univesity of Manchester, UK.
    Mick, Gérard
    Pain Centre, Neurological Hospital, Lyon, France.
    Ortolani, Sergio
    Instituto Auxologico, Milan, Italy.
    Perrot, Serge
    Rheumatology Department, Hospital Tarnier, Paris, France.
    Perucho, Alfredo
    Unidad del Dolor, Hospital Ramon y Cajal, Madrid, Spain.
    Semmons, Ian
    Action on Pain, Norfolk, UK.
    Sörensen, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Do strong opioids have a role in the early management of back pain? Recommendations from a European expert panel2005In: Current Medical Research and Opinion, ISSN 0300-7995, E-ISSN 1473-4877, Vol. 21, no 11, p. 1819-1828Article in journal (Other academic)
    Abstract [en]

    Background: Since chronic low back pain (CLBP) is a complex biopsychosocial problem the ideal treatment is multimodal and multidisciplinary. However, in many countries, primary-care physicians care for many people with CLBP and have a pivotal role in selecting patients for more intensive treatments when these are available. Guidelines on the general use of strong opioids in chronic non-cancer pain have been published but, until now, no specific guidelines were available on their use in chronic low back pain. Given the prevalence of CLBP, and the complex nature of this multifactorial condition, it was felt that specific, evidence-based recommendations, with a focus on primary-care treatment, would be helpful. Methods: An expert panel drawn from across Europe including pain specialists, anaesthetists, neurologists, rheumatologists, a general practitioner, an epidemiologist and the chairman of a pain charity was therefore convened. The aim of the group was to develop evidence-based recommendations that could be used as a framework for more specific guidelines to reflect local differences in the availability of specialist pain services and in the legal status and availability of strong opioids. Statements were based on published evidence (identified by a literature search) wherever possible, and supported by clinical experience when suitable evidence was lacking. Recommendations: Strong opioids have a role in the treatment of low back pain when other treatments have failed. They should be prescribed as part of a multimodal, and ideally interdisciplinary, treatment plan. The aim of treatment should be to relieve pain and facilitate rehabilitation.

  • 10.
    Lemming, Dag
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences.
    Graven-Nielsen, T.
    Sörensen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences.
    Arendt-Nielsen, L.
    Gerdle, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences.
    Facilitated temporal summation and generalized hyperalgesia in whiplash associated disorder2008Article in journal (Refereed)
  • 11.
    Lemming, Dag
    et al.
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Graven-Nielsen, Thomas
    Aalborg University, Denmark .
    Sörensen, Jan
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Arendt-Nielsen, Lars
    Aalborg University, Denmark .
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Widespread pain hypersensitivity and facilitated temporal summation of deep tissue pain in whiplash associated disorder: an explorative study of women2012In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 44, no 8, p. 648-657Article in journal (Refereed)
    Abstract [en]

    Objective: Widespread deep tissue pain hyperalgesia was evaluated in women with chronic whiplash associated disorder (n=25) and controls (n=10) using computerized cuff pressure algometry and hypertonic saline infusion. Methods: A pneumatic double-chamber cuff was placed around: (i) the arm and (ii) the leg. Cuff inflation rate was constant and the pain intensity was registered continuously on a visual analogue scale (VAS); thresholds of detection and tolerance were extracted. For assessment of spatial summation the protocol was repeated with a single-chamber cuff inflated around the leg. Temporal summation of pain was assessed from the leg with constant cuff pressure stimulation at 2 different pressure intensities for 10 min. Hypertonic saline was infused in the tibialis anterior muscle. Results: Cuff pressure pain thresholds were lower in subjects with whiplash associated disorder compared with controls (pless than0.05). Tonic pressure stimulation evoked higher maximal VAS and larger areas under the VAS curve in subjects with whiplash associated disorder compared with controls (pless than0.05). The pain threshold and tolerance were higher during single cuff than double cuff stimulation. The area under the VAS curve after intramuscular saline infusion was larger in whiplash associated disorder (pless than0.05). Conclusion: The results indicated widespread hyperalgesia in chronic whiplash associated disorder and facilitated temporal summation outside the primary pain area, suggesting involvement of central sensitization.

  • 12.
    Lemming, Dag
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences.
    Sörensen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences.
    Graven-Nielsen, Thomas
    Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Denmark.
    Arendt-Nielsen, Lars
    Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Denmark.
    Gerdle, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences.
    The responses to pharmacological challenges and experimental pain in patients with chronic whiplash-associated pain2005In: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 21, no 5, p. 412-421Article in journal (Refereed)
    Abstract [en]

    Objectives: This study evaluates the analgesic responses to intravenous administration of morphine, lidocaine, and ketamine and their relations to duration of chronic pain after whiplash trauma. In addition, experimental muscle pain sensitivity and its correlation to pain duration and pharmacological responses were assessed.

    Methods: Thirty-three patients with diagnosed whiplash-associated disorder grade II in the chronic stage, according to the Quebec classification, were included. The pharmacological evaluation was performed in a randomized, double-blind, cross-over design and consisted of a 30-minute period of intravenous administration of morphine (0.3 mg/kg), lidocaine (5 mg/kg), ketamine (0.3 mg/kg), or placebo (isotonic saline). Intensity ratings of habitual pain on a visual analogue scale were taken before, during, and after the infusion. The patients were classified as nonresponders, placebo-responders, or responders (minimum 50% decrease of pain intensity) of the drugs. Pressure pain thresholds and intramuscular and cutaneous electrical stimulation pain thresholds were measured. The pain intensity during experimental muscle pain by intramuscular hypertonic saline was also recorded. Experimental pain assessments were performed on the lower legs outside the habitual painful area.

    Results: Thirty patients completed the study; 2 were placebo responders and 10 were nonresponders. Of 18 responders, there were 15 morphine responders, 11 lidocaine responders, and 14 ketamine responders. In the patients with whiplash-associated disorder duration less than 2 years, 7 responded to morphine, 5 to lidocaine, and 8 to ketamine. In the patients with pain duration longer than 2 years, 8 responded to morphine, 6 to lidocaine, and 6 to ketamine. Thus, no pattern with respect to pain duration was found. Seventeen patients participated in the experimental pain assessment, and no significant differences in the variables of the intramuscular and cutaneous stimulation and intramuscular-induced pain with respect to response to the pharmacological challenges or whiplash-associated disorder duration existed.

    Discussion: The pharmacological challenges identified subgroups of patients with chronic whiplash-associated disorder that might be considered before instituting therapeutic interventions or research. However, the pattern of responses to the pharmacological challenges did not show any clear relationships with pain duration or the experimental pain tests.

  • 13.
    Lemming, Dag
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Sörensen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Graven-Nielsen, Thomas
    Center for Sensory-Motor Interaction (SMI), Laboratory for Experimental Pain Research, Aalborg University, Denmark.
    Lauber, Rolf
    Department of Anesthesiology, University Hospital, Bern, Switzerland.
    Arendt-Nielsen, Lars
    Center for Sensory-Motor Interaction (SMI), Laboratory for Experimental Pain Research, Aalborg University, Denmark.
    Gerdle, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Managing chronic whiplash associated pain with a combination of low-dose opioid (remifentanil) and NMDA-antagonist (ketamine)2007In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 11, no 7, p. 719-732Article in journal (Refereed)
    Abstract [en]

    The aim was to investigate the efficacy of a combination of low-dose remifentanil (REMI) and ketamine (KET) compared to the single drugs and placebo (P) on whiplash associated pain (WAD) in a double-blind, randomized, placebo-controlled, cross-over study.

    Twenty patients with chronic (>1 year) WAD were included. Four different drug combinations were tested in four sessions: placebo/placebo (P/P), placebo/remifentanil (P/REMI), ketamine/placebo (KET/P) and ketamine/remifentanil (KET/REMI). Target concentrations were 1 and 2 ng/ml (stepwise) for remifentanil and 100 ng/ml for ketamine.

    Habitual pain intensity was assessed on a visual analogue scale (VAS). Experimental pain was assessed with electrical stimulation (single and repeated) of tibialis anterior (TA) muscle, pressure pain algometry applied over infraspinatus (IS) and TA muscles and VAS scores after intramuscular hypertonic saline infusion in TA.

    KET/REMI significantly reduced habitual pain. KET/REMI infused at low REMI target concentration (1 ng/ml) significantly elevated electrical intramuscular pain thresholds (single and repeated). Pain thresholds to electrical stimulation were similarly increased by both P/REMI and KET/REMI at 2 ng/ml target concentration. Pressure pain thresholds were increased by both KET/REMI and P/REMI. VAS-scores after intramuscular saline were also similarly decreased by both REMI combinations. Seven out of 20 subjects were non-responders (<50% pain relief). No correlation was found between effects on spontaneous pain and experimental pain.

    KET/REMI showed an analgesic effect on habitual pain. Experimental pain was attenuated by both combinations containing the opioid, however, KET seemed to enhance the effect of REMI on electrical pain thresholds when a low REMI target concentration was used.

  • 14.
    Persson, Mats
    et al.
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Sörensen, Jan
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Whiplash Associated Disorders (WAD): Responses to pharmacological challenges and psychometric tests2012In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 3, no 3, p. 151-163Article in journal (Refereed)
    Abstract [en]

    Objectives

    The present study challenges chronic WhiplashAssociatedDisorders (WAD)-subjects to a pharmacological intravenous (i.v.) test with morphine, ketamine, and active placebo (midazolam). The aim was to describe the short-term responses to drugs and the assumed heterogeneity in the patterns of responses. We related the different responder groups to the results from psychometrictests.

    Methods

    The study includes 95 patients, all with chronic WAD and referred to our departments. They answered a questionnaire including the following psychometric instruments relevant for chronic pain: Beck Depression Inventory, Coping Strategies Questionnaire, Multidimensional Pain Inventory, Life Satisfaction Checklist, SF36 and EuroQol. The subjects also went through sessions with separate infusions of morphine (0.3 mg/kg), ketamine (0.3 mg/kg) and midazolam (0.05 mg/kg). Infusion time was 30 min followed by a 2-h post-infusion assessment. Assessments were made using a Visual Analogue Scale (VAS) for pain intensity and unpleasantness and by statements of per cent pain relieved. A categorical pain rating scale was also used. A positive response was defined as ≥50% decrease of the VAS-level on two consecutive assessment points during the test sessions, anything less was a non response. The placebo responders were defined as those with a positive response to the active placebo infusion.

    Results

    The tests were completed by 94 subjects and 26% of these were placebo responders. Among the placebo non responders, 47% responded to morphine, 41% to ketamine, 25% to both drugs and 37% to neither morphine nor ketamine (pain intensity assessments). Similar proportions were found in the assessments of pain unpleasantness and per cent pain relieved. Approximately one in four subjects (27%, pain intensity assessment) did not respond to any of the drugs tested. This relatively high proportion of non responders seemed to be worst cases in some aspects of the psychometrictests. Generally, this non responder group had a trend to score worse for most items in the psychometrictests with some reaching significance in a univariate analysis. This result was confirmed in a multivariate context, although the results indicated only small differences between the groups. All three substances showed significant pain relief compared to baseline on all assessment points. On most variables, morphine and ketamine were significantly more effective compared to the active placebo.

    Conclusions

    There are different subgroups among subjects with chronic WAD with variations in responses to i.v. morphine, ketamine, and midazolam (active placebo). Subjects with chronic WAD who did not respond to any of the drugs tested scored badly in some aspects of the psychometric instruments.

    Implications

    The present study confirms one aspect of the heterogeneity in the population with chronic WAD. The study does not elucidate precise pain mechanisms but taken together with other studies exploring other aspects, it stresses the importance of individualizing the assessment and treatment of subjects with chronic WAD. A common clinical experience is that depression, anxiety and maladaptive coping strategies often are obstacles for successful medical treatment of chronic pain. The present study supports this experience and emphasizes the need for assessment of psychometric variables when planning the treatment of chronic WAD.

  • 15.
    Rosendahl, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Larsson, Britt
    Kristiansen, Jesper
    Peolsson, Michael
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine.
    Sögaard, Karen
    Kjaer, Michael
    Sörensen, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Gerdle, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Increase in muscle nociceptive substances and anaerobic metabolism in patients with trapezius myalgia: Microdialysis in rest and during exercise2004In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 112, no 3, p. 324-334Article in journal (Refereed)
    Abstract [en]

    Local metabolic changes are suggested to be involved in muscle pain development in humans. Nineteen women with chronic work-related trapezius myalgia (TM) and 20 healthy female controls (CON) were studied during baseline rest, 20 min repetitive low-force exercise, and 120 min recovery. Interstitial serotonin (5-HT), glutamate, lactate, pyruvate, and blood flow were determined by microdialysis in the trapezius muscle. Baseline pressure pain threshold (PPT) was lower (143±18 (TM) vs. 269±17 (CON) kPa) (mean±SEM), pain intensity (visual analogue scale, VAS) higher (33±5 vs. 2±1 mm), muscle 5-HT higher (22.9±6.7 vs. 3.8±1.3 nmol/l), and glutamate higher (47±3 vs. 36±4 μmol/l) in TM than in CON (all P<0.05), whereas muscle blood flow was similar in groups. Furthermore, muscle pyruvate was higher (180±15 vs. 135±12 μmol/l) and lactate higher (4.4±0.3 vs. 3.1±0.3 mmol/l) in TM than in CON (P<0.001). In response to exercise, VAS and glutamate increased in both TM and CON (all P<0.05). In TM only, lactate and pyruvate increased significantly (P<0.02), whereas blood flow increased to similar levels in both groups. During the initial 20 min recovery period, blood flow remained increased in TM (P<0.005) whereas it decreased to baseline levels in CON. In conclusion, patients with chronic work-related TM have increased levels of muscle 5-HT and glutamate that were correlated to pain intensity (r=0.55, P<0.001) and PPT (r=-0.47, P<0.001), respectively. In addition, TM was associated with increased anaerobic metabolism, whereas a normal rise in blood flow was seen with exercise. These findings indicate that peripheral nociceptive processes are active in work-related TM. © 2004 International Association for the Study of Pain.

  • 16.
    Rosendal, Lars
    et al.
    Arbetsmiljöinstitutet, Köpenhamn, Danmark.
    Kristiansen, Jesper
    Arbetsmiljöinstitutet, Köpenhamn, Danmark.
    Gerdle, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Sögaard, Karen
    Arbetsmiljöinstitutet, Köpenhamn, Danmark.
    Peolsson, Michael
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine.
    Kjaer, Michael
    Bispebjerg sjukhus, Köpenhamn, Danmark.
    Sörensen, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Larsson, Britt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Increased levels of interstitial potassium but normal levels of muscle IL-6 and LDH in patients with trapezius myalgia2005In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 119, no 1-3, p. 201-209Article in journal (Refereed)
    Abstract [en]

    The mechanisms behind the development of work-related trapezius pain are suggested to involve both peripheral and central components, but the specific contribution of alterations in muscle nociceptive and other substances is not clear. Female patients with chronic trapezius myalgia (N=19, TM) and female controls (N=20, CON) were studied at rest, during 20 min repetitive low-force exercise and recovery, and had their interstitial concentrations of potassium (K+), lactate dehydrogenase (LDH), interleukin-6 (IL-6) and collagen turnover determined in the trapezius muscle by the microdialysis technique. K+ levels were at all time points higher in TM than in CON (P<0.0001). Baseline levels of LDH and IL-6 were similar in both groups. In response to exercise pain intensity, rated perceived exertion, and the concentrations of K+, LDH and IL-6 increased significantly in both groups. [K+] immediately decreased to baseline levels in CON but remained elevated during the first 20 min of recovery in TM (P<0.01) whereafter it returned to baseline level. In all subjects taken together mean [K+] correlated negatively with pressure pain threshold of trapezius (P<0.001), positively with mean pain intensity VAS (P<0.001) and mean perceived exertion (P<0.001). Rises in muscle LDH and IL-6 as well as the anabolic ratio for collagen type I was not significantly different between groups. In conclusion, patients with chronic pain in the trapezius muscle had increased levels of interstitial potassium. This finding could be causally related to myalgia or secondary to pain due to deconditioned muscle or altered muscle activity pattern. © 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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