Eija Kalso

Helsinki University Central Hospital, Helsinki, Uusimaa, Finland

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Publications (150)732.43 Total impact

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    ABSTRACT: Background Patients with widespread unilateral chronic pain associated with recurrent herpes simplex virus (HSV) infections show functional and/or structural changes in the insula, anterior cingulate cortex, frontal and prefrontal cortices, as well as the thalamus, suggesting central dysfunction of the pain system in these patients. Central pain has been associated with attenuated laser-evoked cortical responses. We aimed to clarify whether the observed deficient activation of these areas to acute nociceptive stimuli is due to a lesion at a lower level of pain processing pathways.Methods We explored the functional integrity of the ascending nociceptive pathways by recording the cortical-evoked responses to noxious laser stimulation using magnetoencephalography and electroencephalography in eight patients (age 41–51 years, mean 46) with recurrent HSV infections and a history of chronic, spontaneous, widespread unilateral pain, and in nine age-matched healthy control subjects.ResultsThe cortical-evoked fields of the HSV patients originating from the secondary somatosensory and posterior parietal cortices, as well as the evoked potentials recorded from the midline, did not differ from those of the control subjects, indicating functionally intact ascending nociceptive pathways.Conclusions The present results show that our patients with chronic hemibody pain do not show signs of spinothalamic tract lesion. This indicates normal processing of sensory aspects of painful stimuli, while higher pain processing areas show altered activation. We conclude that normal laser-evoked magnetic fields (LEF) or laser-evoked potentials (LEP) may not exclude central pain condition.
    European journal of pain (London, England) 08/2015; 19(8). DOI:10.1002/ejp.642 · 2.93 Impact Factor
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    ABSTRACT: Chronic pain affects a large proportion of the population, imposing significant individual distress and a considerable burden on society, yet treatment is not always instituted and/or adequate. Comprehensive multidisciplinary management based on the biopsychosocial model of pain has been shown to be clinically effective and cost-efficient, but is not widely available. A literature review of stakeholder groups revealed many reasons for this, including: i.) many patients believe healthcare professionals lack relevant knowledge, and consultations are rushed, ii.) general practitioners consider that pain management has a low priority and is under-resourced, iii.) pain specialists cite non-adherence to evidence-based treatment, sub-optimal prescribing, and chronic pain not being regarded as a disease in its own right, iv.) nurses', pharmacists' and physiotherapists' skills are not fully utilised, and v.) psychological therapy is employed infrequently and often too late. Many of the issues relating to physicians could be addressed by improving medical training, both at undergraduate and postgraduate levels - for example, by making pain medicine a compulsory core subject of the undergraduate medical curriculum. This would improve physician/patient communication, increase the use of standardised pain assessment tools, and allow more patients to participate in treatment decisions. Patient care would also benefit from improved training for other multidisciplinary team members; for example, nurses could provide counselling and follow-up support, psychologists offer coping skills training, and physiotherapists have a greater role in rehabilitation. Equally important measures include the widespread adoption of a patient-centred approach, chronic pain being recognised as a disease in its own right, and the development of universal guidelines for managing chronic non-cancer pain. Perhaps the greatest barrier to improvement is lack of political will at both national and international level. Some powerful initiatives and collaborations are currently lobbying policy-making bodies to raise standards and reduce unnecessary pain - it is vital they continue.
    Current Medical Research and Opinion 07/2015; 31(9):1-37. DOI:10.1185/03007995.2015.1072088 · 2.65 Impact Factor
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    ABSTRACT: Background Oxycodone is increasingly being used in combination with pregabalin. Pregabalin use is prevalent in opioid-dependent individuals. A high number of deaths caused by the co-use of gabapentinoids and opioids occur. It is not known whether pregabalin affects concentrations of oxycodone or morphine in the central nervous system.Methods Effects of pregabalin on acute oxycodone or morphine-induced antinociception, tolerance and sedation were studied using tail-flick, hot plate and rotarod tests in male Sprague–Dawley rats. Concentrations of pregabalin, opioids and their major metabolites in the brain were quantified by mass spectrometry.ResultsIn the hot plate test, morphine (2.5 mg/kg, s.c.) caused antinociception of 28% maximum possible effect (MPE), whereas pregabalin (50 mg/kg, i.p.) produced 8–10% MPE. Co-administration of pregabalin and morphine resulted in antinociception of 63% MPE. Oxycodone (0.6 mg/kg s.c.) produced antinociception of 18% MPE, which increased to 39% MPE after co-administration with pregabalin. When pregabalin 10 mg/kg was administered before oxycodone (0.6 mg/kg, s.c.) or morphine (2.5 mg/kg), only the effect of oxycodone was potentiated in the tail-flick and the hot plate tests. Brain concentrations of the opioids, their major metabolites and pregabalin were unchanged. Pregabalin co-administration (50 mg/kg, i.p., once daily) did not prevent the development of morphine tolerance.Conclusions Pregabalin potentiated antinociceptive and sedative effects of oxycodone and morphine in acute nociception. Co-administration of pregabalin with the opioids did not affect the brain concentrations of oxycodone or morphine. Pregabalin did not prevent morphine tolerance.
    European journal of pain (London, England) 05/2015; DOI:10.1002/ejp.728 · 2.93 Impact Factor
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  • Survey of Anesthesiology 04/2015; 59(2):98-99. DOI:10.1097/01.SA.0000461276.90838.5a
  • J Hotta · H Harno · L Nummenmaa · E Kalso · R Hari · N Forss
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    ABSTRACT: Movement accuracy is ensured by interaction between motor, somatosensory, and visual systems. In complex regional pain syndrome (CRPS), this interaction is disturbed. To explore CRPS patients' visual perception of actions, we investigated how these patients evaluate the applied force in observed hand actions of another person. Nineteen patients suffering from unilateral upper-limb CRPS and 19 healthy control subjects viewed six different videos of left- and right-hand actions. They were asked to evaluate the applied force in each hand action, as well as their subjective sensations of unpleasantness and pain during the observation. The patients overestimated the force applied in the videos: the ratings were two times as large as in the control subjects for actions performed with the hand corresponding to the patients' affected hand, and 1.5 times as large for actions corresponding to their healthy hand. The control subjects considered the stimuli neutral and painless, whereas the patients rated them unpleasant. Moreover, the patients felt increased pain during viewing actions performed with the hand corresponding to their affected side. The overestimation of force was related to the elicited unpleasantness and pain, but not to the patients' muscle strength. We propose that the overestimation of force is explained both by the pain elicited by the observation and by the abnormal sensorimotor integration that is associated with perception of increased effort. This visually elicited unpleasantness and painfulness may promote avoidance of viewing own actions, further impairing the patients' motor performance. © 2015 European Pain Federation - EFIC®
    European journal of pain (London, England) 03/2015; DOI:10.1002/ejp.669 · 2.93 Impact Factor
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    ABSTRACT: Low-dose ketamine is a lucrative therapeutic approach in cancer pain, perioperative treatment of pain, and management of treatment-resistant depression. The analgesic potency of its main metabolite norketamine is thought to be one third that of ketamine. However, few studies exist on the pharmacokinetics of orally administered S-ketamine. In our study, 11 healthy volunteers received S-ketamine 0.25 mg/kg orally and 0.125 mg/kg intravenously. S-ketamine and norketamine concentrations were measured up to 23.5 h post-dose. A population pharmacokinetic model was built to describe S-ketamine and norketamine pharmacokinetics. A three-compartment model for both S-ketamine and norketamine best described the data. To accommodate for the extensive formation of norketamine after oral S-ketamine, a separate presystemic absorption-phase component was included in addition to its systemic formation. The oral bioavailability of S-ketamine was low, 8 % (11 % interindividual variability), and its clearance was high, 95 L/h/70 kg (13 % interindividual variability). Simulations suggested that after oral dosing, norketamine AUC at steady state is 16.5 times higher than that of S-ketamine. Given that the analgesic effect of S-ketamine is due to both S-ketamine and norketamine, relatively small oral doses of S-ketamine can be assumed to be a feasible alternative to repeated intravenous dosing, for example in the setting of chronic pain.
    European Journal of Clinical Pharmacology 03/2015; 71(4). DOI:10.1007/s00228-015-1826-y · 2.97 Impact Factor
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    ABSTRACT: Background and purpose: The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental approach: Morphine minipumps (6 mg·day(-1) ) induced tolerance during 5 days in Sprague-Dawley rats, after which s.c. ketamine (10 mg·kg(-1) ) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key results: In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and implications: The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans.
    British Journal of Pharmacology 10/2014; 172(11). DOI:10.1111/bph.12974 · 4.84 Impact Factor
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    ABSTRACT: In 2010, a quarter of direct healthcare cost in Europe were spent on brain diseases. The importance of preventing and treating brain diseases and maintaining of functional capacity of the brain will increase in our society with ageing population and with increasing cognitive requirements of modern working life. Public funding of basic and clinical neuroscience has, however, frozen to levels achieved years ago, clinical research of brain diseases being at a particular risk. Research projects directed to prevention, treatment, and rehabilitation of brain diseases will pay off, also when assessed by economic measures.
    Duodecim; lääketieteellinen aikakauskirja 10/2014; 130(17):1721-30.
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    ABSTRACT: Context Measuring opioid concentrations in pain treatment is warranted in situations where optimal opioid analgesia is difficult to reach. Objectives To assess the usefulness of oral fluid (OFL) as an alternative to plasma in opioid concentration monitoring in cancer patients on chronic opioid therapy. Methods We collected OFL and plasma samples from 64 cancer patients on controlled-release (CR) oral morphine, CR oral oxycodone or transdermal (TD) fentanyl for pain. Samples were obtained on up to five separate days. Results A total of of 213 OFL and plasma samples were evaluable. All patients had detectable amounts of the CR or TD opioid in both plasma and OFL samples. The plasma concentrations of oxycodone and fentanyl (determination coefficient R2 = 0.628 and 0.700, respectively), but not morphine (R2 = 0.292), were moderately well correlated to the daily opioid doses. In contrast to morphine and fentanyl (mean OFL/plasma ratio 2.0 and 3.0, respectively), the OFL oxycodone concentrations were significantly higher than the respective plasma concentrations (mean OFL/plasma ratio 14.9). An active transporter could explain the much higher OFL versus plasma concentrations of oxycodone compared with morphine and fentanyl. Conclusion OFL analysis is well suited for detecting the studied opioids. For morphine and fentanyl, an approximation of the plasma opioid concentrations is obtainable, whereas for oxycodone, the OFL/plasma concentration relationship is too variable for reliable approximation results.
    Journal of Pain and Symptom Management 09/2014; DOI:10.1016/j.jpainsymman.2014.09.004 · 2.80 Impact Factor
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    ABSTRACT: Unlabelled: Most clinically used opioids are mu-opioid receptor agonists. Therefore, genetic variation of the OPRM1 gene that encodes the mu-opioid receptor is of great interest for understanding pain management. A polymorphism 118A>G (rs1799971) within the OPRM1 gene results in a missense mutation and affects the function of the receptor. We studied the association between the 118A>G polymorphism and oxycodone analgesia and pain sensitivity in 1,000 women undergoing breast cancer surgery. Preoperatively, experimental cold and heat pain sensitivities were tested. Postoperative pain was assessed at rest and during motion. Intravenous oxycodone analgesia was titrated first by a research nurse and on the ward using a patient-controlled analgesia device. The primary endpoint was the amount of oxycodone needed for the first state of adequate analgesia. For each patient, the 118A>G polymorphism was genotyped using the Sequenom MassARRAY (Sequenom, San Diego, CA). The association between this variant and the pain phenotypes was tested using linear regression. The 118A>G variant was associated significantly with the amount of oxycodone requested for adequate analgesia (P = .003, β = .016). Collectively, oxycodone consumption was highest in individuals having the GG genotype (.16 mg/kg), lowest for those with the AA genotype (.12 mg/kg), and moderate for those having the AG genotype (.13 mg/kg). Furthermore, the G allele was associated with higher postoperative baseline pain ratings (P = .001, β = .44). No evidence of association with other pain phenotypes examined was observed. Perspective: This study demonstrates that the OPRM1 118A>G polymorphism was associated with the amount of oxycodone required in the immediate postoperative period. Although a significant factor for determining oxycodone requirement, the 118A>G polymorphism alone explained less than 1% of the variance. No association was found between 118A>G and experimental pain
    Journal of Pain 09/2014; 15(12). DOI:10.1016/j.jpain.2014.09.002 · 4.01 Impact Factor
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    ABSTRACT: Background: This review evaluates trials of antidepressants for acute and chronic postsurgical pain. Methods: Trials were systematically identified using predefined inclusion and exclusion criteria. Extracted data included the following: pain at rest and with movement, adverse effects, and other outcomes. Results: Fifteen studies (985 participants) of early postoperative pain evaluated amitriptyline (three trials), bicifadine (two trials), desipramine (three trials), duloxetine (one trial), fluoxetine (one trial), fluradoline (one trial), tryptophan (four trials), and venlafaxine (one trial). Three studies (565 participants) of chronic postoperative pain prevention evaluated duloxetine (one trial), escitalopram (one trial), and venlafaxine (one trial). Heterogeneity because of differences in drug, dosing regimen, outcomes, and/or surgical procedure precluded any meta-analyses. Superiority to placebo was reported in 8 of 15 trials for early pain reduction and 1 of 3 trials for chronic pain reduction. The majority of positive trials did not report sufficient data to estimate treatment effect sizes. Many studies had inadequate size, safety evaluation/reporting, procedure specificity, and movement-evoked pain assessment. Conclusions: There is currently insufficient evidence to support the clinical use of antidepressants-beyond controlled investigations-for treatment of acute, or prevention of chronic, postoperative pain. Multiple positive trials suggest the therapeutic potential of antidepressants, which need to be replicated. Other nontrial evidence suggests potential safety concerns of perioperative antidepressant use. Future studies are needed to better define the risk-benefit ratio of antidepressants in postoperative pain management. Higher-quality trials should optimize dosing, timing and duration of antidepressant treatment, trial size, patient selection, safety evaluation and reporting, procedure specificity, and assessment of movement-evoked pain relevant to postoperative functional recovery.
    Anesthesiology 09/2014; 121(3):591-608. DOI:10.1097/ALN.0000000000000307 · 5.88 Impact Factor
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    ABSTRACT: Objective: We describe the frequency, duration, clinical characteristics, and radiologic correlates of central poststroke pain (CPSP) in young ischemic stroke survivors in a prospective study setting. Methods: A questionnaire of pain and sensory abnormalities and EQ-5D quality-of-life questionnaire were sent to all 824 surviving and eligible patients of the Helsinki Young Stroke Registry. Patients (n = 58) with suspected CPSP were invited to a clinical visit and filled in the PainDETECT, Brief Pain Inventory, and Beck Depression Inventory questionnaires. Results: Of the included 824 patients, 49 had CPSP (5.9%), 246 patients (29.9%) had sensory abnormality without CPSP, and 529 patients (64.2%) had neither sensory abnormality nor CPSP. The median follow-up time from stroke was 8.5 years (interquartile range 5.0-12.1). Patients with CPSP had low quality of life compared to those with sensory abnormality without CPSP (p = 0.007) as well as to those with no sensory abnormality and no CPSP (p < 0.001). Forty (82%) of the patients with CPSP had concomitant other pain. CPSP was associated with moderate (p < 0.001) and severe (p < 0.001) stroke symptoms, but there was no difference in age at stroke onset or subtype of stroke according to the TOAST classification between the groups. Stroke localization was not correlated with CPSP. Conclusions: Late persistent CPSP was found in 5.9% of young stroke survivors and was associated with concomitant other pain, impaired quality of life, and moderate or severe stroke symptoms.
    Neurology 08/2014; 83(13). DOI:10.1212/WNL.0000000000000818 · 8.29 Impact Factor
  • Andrew Moore · Philip Wiffen · Eija Kalso
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    ABSTRACT: Clinical question: Are antiepileptic drugs associated with reduced pain intensity in patients with neuropathic pain or fibromyalgia? Bottom line: In treating diabetic neuropathy and postherpetic neuralgia compared with placebo, gabapentin and pregabalin are associated with a modest increase in the number of patients experiencing meaningful pain reduction. In treating fibromyalgia, compared with placebo, pregabalin alone is associated with a small increase in the number of patients experiencing meaningful pain reduction. There is insufficient evidence for other antiepileptics.
    JAMA The Journal of the American Medical Association 07/2014; 312(2):182-3. DOI:10.1001/jama.2014.6336 · 35.29 Impact Factor
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    ABSTRACT: Background and aims Thoracotomies can cause severe pain, which persists in 21–67% of patients. We investigated whether NSAID + intravenous patient-controlled analgesia (IV-PCA) with morphine is an efficacious alternative to thoracic epidural analgesia (TEA). We also wanted to find out whether an extended controlled pain management protocol within a clinical study can decrease the incidence of persistent post-thoracotomy pain. Methods Thirty thoracotomy patients were randomized into 3 intervention groups with 10 patients in each. G1: preoperative diclofenac 75 mg orally + 150 mg/24 h IV for 44 h, then PO; G2: valdecoxib 40 mg orally + parecoxib 80 mg/24 h IV for 44 h, then PO. IV-PCA morphine was available in groups 1 and 2 during pleural drainage, and an intercostal nerve block at the end of surgery was performed; G3: paracetamol + patient controlled epidural analgesia (PCEA) with a background infusion of bupivacaine with fentanyl. After PCA/PCEA oxycodone PO was provided when needed. These patients were contacted one week, 3 and 6 months after discharge. Patients (N = 111) not involved in the study were treated according to hospital practice and served as a control group. The control patients’ data from the perioperative period were extracted, and a prospective follow-up questionnaire at 6 months after surgery similar to the intervention group was mailed. Results The intended sample size was not reached in the intervention group because of the global withdrawal of valdecoxib, and the study was terminated prematurely. At 6 months 3% of the intervention patients and 24% of the control patients reported persistent pain (p < 0.01). Diclofenac and valdecoxib provided similar analgesia, and in the combined NSAID group (diclofenac + valdecoxib) movement-related pain was milder in the PCEA group compared with the NSAID group. The duration of pain after coughing was shorter in the PCEA group compared with the NSAID + IV-PCA group. The only patient with persistent pain at 6 months postoperatively had a considerably longer duration of pain after coughing than the other Study patients. The patients with mechanical hyperalgesia had more pain on movement. Conclusions Both PCEA and NSAID + IV-PCA morphine provided sufficient analgesia with little persistent pain compared with the incidence of persistent pain in the control group. High quality acute pain management and follow-up continuing after discharge could be more important than the analgesic method per se in preventing persistent post-thoracotomy pain. In the acute phase the measurement of pain when coughing and the duration of pain after coughing could be easy measures to recognize patients having a higher risk for persistent post-thoracotomy pain. Implications To prevent persistent post-thoracotomy pain, the extended protocol for high quality pain management in hospital covering also the sub-acute phase at home, is important. This study also provides some evidence that safe and effective alternatives to thoracic epidural analgesia do exist. The idea to include the standard “as usual” care patients as a control group and to compare them with the intervention patients provides valuable information of the added value of being a study patient, and deserves further consideration in future studies.
    Scandinavian Journal of Pain 07/2014; 5(4). DOI:10.1016/j.sjpain.2014.07.001
  • Clinical Neurophysiology 06/2014; 125:S311. DOI:10.1016/S1388-2457(14)51025-5 · 3.10 Impact Factor
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    ABSTRACT: Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine whether a treatment is likely to be efficacious for a given indication and thus whether it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge in designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost-effective manner. An IMMPACT consensus meeting was convened to discuss design considerations for POC trials in analgesia, with a focus on maximizing power with limited resources and participants. We present general design aspects to consider including patient population, active comparators and placebos, study power, pharmacokinetic-pharmacodynamic relationships, and minimization of missing data. Efficiency of single-dose studies for treatments with rapid onset is discussed. The trade-off between parallel-group and crossover designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages of more recent trial designs, including N-of-1 designs, enriched designs, adaptive designs, and sequential parallel comparison designs, are summarized, and recommendations for consideration are provided. More attention to identifying efficient yet powerful designs for POC clinical trials of chronic pain treatments may increase the percentage of truly efficacious pain treatments that are advanced to confirmatory trials while decreasing the percentage of ineffective treatments that continue to be evaluated rather than abandoned.
    Pain 05/2014; 155(9). DOI:10.1016/j.pain.2014.05.025 · 5.21 Impact Factor
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    ABSTRACT: Abstract Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients' reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient's rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms - not simply based on pain intensity, as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level.
    Current Medical Research and Opinion 05/2014; 30(9):1-0. DOI:10.1185/03007995.2014.925439 · 2.65 Impact Factor
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    ABSTRACT: Pregabalin (PRG) and gabapentin (GBP) are used in the treatment of neuropathic pain and epilepsy, and PRG also in generalized anxiety disorder. There is increasing evidence that PRG possesses considerable abuse potential. PRG may have a higher addiction potential than GBP due to its rapid absorption and faster onset of action. Our objective is to estimate the proportion of all PRG- and GBP-related fatalities attributable to PRG and GBP abuse. We investigated all medico-legal death cases in Finland in which PRG or GBP was found in postmortem toxicology during 2010-2011. PRG was found in 316 cases and GBP in 43 cases. Drug abuse was associated with 48.1% of the PRG and 18.6% of the GBP findings. PRG poisoning accounted for 10.1% of all PRG cases and GBP poisoning for 4.7% of all GBP cases. In the drug abuser cases, PRG poisoning represented 19.1%, and GBP poisoning 12.5%. The median blood concentration of PRG was 15mg/L in the abuser group and 5.8mg/L in the other cases. For GBP, these concentrations were 12mg/L and 8.3mg/L, respectively. In the PRG abuser group, 91.4% of cases showed concomitant opioid use, while in the rest of these cases neither alcohol nor opioids were detected, but other central nervous system acting drugs were found in each abuser case. In the GBP abuser group, 87.5% of cases showed concomitant opioid use. PRG abuse with high doses is increasingly common and can be fatal when combined with opioids.
    Forensic Science International 05/2014; 241C:1-6. DOI:10.1016/j.forsciint.2014.04.028 · 2.14 Impact Factor
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    ABSTRACT: Neuropathic pain is pain coming from damaged nerves. It is different from pain messages carried along healthy nerves from damaged tissue (a fall, or cut, or arthritic knee). Neuropathic pain is treated by different medicines than pain from damaged tissue. Medicines like paracetamol or ibuprofen are not effective in neuropathic pain, while medicines that are sometimes used to treat depression or epilepsy can be very effective in some people with neuropathic pain. Our understanding of fibromyalgia (a condition of persistent, widespread pain and tenderness, sleep problems, and fatigue) is lacking, but fibromyalgia can respond to the same medicines as neuropathic pain. Lamotrigine is a medicine used to treat epilepsy, and so might be a useful medicine for neuropathic pain or fibromyalgia. On 26 November 2013 we performed searches to look for clinical trials where lamotrigine was used to treat neuropathic pain or fibromyalgia. We found 12 studies of reasonable quality that tested lamotrigine against placebo for a number of weeks. Almost half of the 1511 people in the studies had painful limbs because of damaged nerves caused by diabetes, and seven different painful neuropathic conditions were examined. No studies looked at fibromyalgia. Lamotrigine did not help the pain, and was no different from placebo except in causing more side effects. Adverse events were more frequent with lamotrigine than placebo, with rash in 1 person in 27.
    Cochrane database of systematic reviews (Online) 04/2014; 4(12):CD005451. DOI:10.1002/14651858.CD005451.pub3 · 6.03 Impact Factor

Publication Stats

6k Citations
732.43 Total Impact Points


  • 1998–2015
    • Helsinki University Central Hospital
      • Department of Oncology
      Helsinki, Uusimaa, Finland
  • 1991–2015
    • University of Helsinki
      • • Institute of Biomedicine
      • • Institute of Clinical Medicine
      • • Faculty of Pharmacy
      • • Division of Pharmacology and Toxicology
      • • Department of Anaesthesia
      Helsinki, Uusimaa, Finland
  • 2013
    • University of Oxford
      Oxford, England, United Kingdom
  • 2011
    • Central Hospital Central Finland
      Jyväskylä, Province of Western Finland, Finland
  • 2004
    • Hospital District for Helsinki and Uusimaa
      Helsinki, Southern Finland Province, Finland
  • 1997
    • Åbo Akademi University
      • Department of Biology
      Turku, Province of Western Finland, Finland