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ABSTRACT: Experimental studies suggest that paracetamol-induced analgesia is mediated via central serotonergic pathways and attenuated by 5-HT3-antagonists. However, clinical studies do not support this, and 5-HT3-antagonists are expected to reduce pain by blocking the descending pronociceptive pathway. The current project tested whether tropisetron attenuates analgesia by paracetamol. Two randomized, double-blind, crossover studies with 18 healthy male volunteers in each were performed. Pain stimuli were cold water immersion (cold pressor test), contact heat pain (study 1) and electrical stimulation (study 2). In both studies, tropisetron 5 mg i.v. or saline was administered, followed by paracetamol 2 g i.v. 30 min. later. Individual changes in heat and cold pain intensity, cold pain tolerance and unpleasantness were recorded. The same thresholds were also expressed as scores (% of the individual score at baseline). Additionally, previously published findings on the effects of paracetamol and its interaction with 5HT3-antagonists in human experimental pain models were reviewed. After calculation of the sensory and pain scores (%), tropisetron seemed to amplify the analgesic action of paracetamol. Paracetamol 2 g i.v. did not show any statistically significant analgesia in thermal tests (study 1), or differences in sensory, pain detection or moderate pain thresholds of the electrical stimulus (study 2). As paracetamol did not have a measurable analgesic effect in these tests, no conclusions can be drawn about the interaction between paracetamol and tropisetron. However, tropisetron may have an analgesic effect of its own. Clinicians should not avoid using these drugs together, unless larger clinical studies indicate otherwise.
Basic & Clinical Pharmacology & Toxicology 08/2012; · 2.18 Impact Factor
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ABSTRACT: Opioids are increasingly used to manage not only acute but also chronic pain and heroine addiction. These patients usually receive many other medications that can interfere with the effects of opioids and vice versa. Patients often need combinations of drugs for their pain management, for treating opioid-related adverse effects or for other indications including depression and anxiety. Several antibiotics can also have interactions with opioids. It is important to understand what potential interactions exist between opioids and other drugs. Drug interactions can occur due to pharmacokinetic interactions including effects of absorption, metabolic pathways, drug transport through membranes and protein binding. Our knowledge of the metabolism of opioids has significantly increased over the last years and it now possible to appreciate the role CYP enzymes, mainly CYP 2D6 and 3A4/5, in the metabolism of many commonly used opioids like codeine and oxycodone. Our knowledge regarding the role of the transporter proteins in drug interactions related to opioids is unfortunately meagre. Opioids inhibit the gastrointestinal system and can thus change the absorption of other drugs. Opioids can have synergistic or additive interactions with other drugs that have analgesic or sedative effects. Endogenous opioids control many physiological functions and exogenous opioids can have effects on all important transmitter systems (cholinergic, GABAergic, dopaminergic and serotonergic). The literature in this field is mainly based on case reports. Interindividual differences play an important role. Other potential interactions include prolongation of the QT-interval and lowering of the threshold for convulsions.
Current pharmaceutical design 06/2012; · 4.41 Impact Factor
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Pain 02/2012; 153(4):935-6. · 5.78 Impact Factor
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ABSTRACT: Anxiety symptoms are common in chronic pain patients. High levels of anxiety are associated with increased pain experience and disability. Proneness to anxiety has a large interindividual variation. The aim of the study was to determine whether the anxiety-related temperament trait Harm Avoidance (HA), is associated with pain-related anxiety.
One hundred chronic pain patients in a multidisciplinary pain clinic participated in the study. The patients were assessed using the HA scale of the Temperament and Character Inventory (TCI) of Cloninger and Pain Anxiety Symptoms Scale-20 (PASS-20). Both the HA total score and the four subscales of HA were analyzed. Current pain intensity was measured using the Visual Analogue Scale (VAS). The Beck Depression Inventory (BDI) was used to control for the influence of depression on the personality measurement.
The HA total score was associated with PASS-20, but the association became non-significant after controlling for depression. The HA4 Fatigability subscale was associated with the PASS scales. Depression did not influence this association. Pain intensity was not correlated with HA or the PASS scales. However, the association between HA4 Fatigability and PASS was influenced by pain intensity. Higher pain intensity was associated with stronger association between the scales.
Harm Avoidance, representing temperament and trait-related anxiety, has relevance in pain-related anxiety. Assessing personality and temperament may deepen the clinician's understanding of the pain experience and behavior in chronic pain patients.
PLoS ONE 01/2012; 7(10):e45672. · 4.09 Impact Factor
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ABSTRACT: The aim of the study was to compare two different neurotoxicity scales in grading chemotherapy-induced neurotoxicity.
The study sample consisted of 114 cancer patients who started chemotherapy with vinca alcaloids, platinum derivatives or taxanes. Neurotoxicity was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) and oxaliplatin scales at baseline and after every third chemotherapy cycle thereafter.
Neuropathy was detected in 60%, 55% and 75% at the second, third and fourth visits, respectively, with the NCI-CTC sensory scale and 59%, 55% and 80% with the oxalipalatin scale. Of the patients with grade 3-4 toxicity on the oxaliplatin scale, 23/53 had grade 1, 18/53 had grade 2 and 12/53 had grade 3 neurotoxicity on the NCI-CTC sensory scale.
The oxaliplatin and NCI-CTC sensory scales were comparable in identifying chemotherapy-induced neuropathy, but the oxaliplatin scale more often detected the progression of the symptoms.
Anticancer research 10/2011; 31(10):3493-6. · 1.73 Impact Factor
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Eija Kalso
Current Medical Research and Opinion 09/2011; 27(10):2069-71. · 2.38 Impact Factor
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Pain 07/2011; 152(10):2204-5. · 5.78 Impact Factor
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ABSTRACT: To assess whether symptoms of fibromyalgia (FM) predict disability retirement or mortality.
All Finnish Twin Cohort members and diagnosed FM-patients who had answered the same health questionnaire in 1990-1992 were studied. A sample of 10,608 working aged individuals of the cohort was classified in homogenous groups based on symptom profile with latent class analysis, using a battery of questions addressing FM-associated symptoms validated between FM-patients and twins. This resulted in three classes: no or few symptoms (LC1), some symptoms (LC2), and high load of FM-symptoms (LC3). In a 14-year follow-up, 1990-2004, information on disability retirement was obtained from official pension registers. Further linkage with Population Register Centre data for 1990-2009 yielded information on the vital status of the cohort subjects. Those with malignancies or inflammatory rheumatic diseases were excluded.
Cumulative incidence of early disability retirement was 9.5% among all 8448 individuals (after exclusions), and 26% in LC3. Adjusted hrs for early retirement were 1.0 (reference class) in LC1, 1.5 (95%CI 1.2-1.7) in LC2, and 2.9 (2.4-3.6) in LC3 for all causes and 1.8 (1.4-2.5) in LC2 and 5.0 (3.6-6.9) in LC3 for musculoskeletal disorders. In 173,675 person-years, the high symptom class (LC3) had a 43% (95% CI 17-75%) increased overall mortality risk, which was fully accounted for by adjustment for lifestyle factors, mainly smoking.
Symptoms associated with FM strongly correlate with early disability retirement. Lifestyle problems associated with high symptom load need prompt management to avoid increased risk of mortality.
European journal of pain (London, England) 02/2011; 15(7):741-7. · 3.37 Impact Factor
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ABSTRACT: Neuropathy is a common adverse effect of chemotherapy. However, the both the prevalence and the burden of this adverse effect have been poorly documented. The aim of the study was to assess the prevalence and discomfort caused by neuropathic symptoms in relation to other adverse effects of chemotherapy.
Between January 2002 and June 2004, we screened 448 patients who were treated with vinca alkaloids, taxanes or platina derivatives, using a simple questionnaire of neuropathic symptoms. The response rate was 75%. Neuropathic symptoms were reported by 258 respondents (76%), of whom 152 patients were eligible for the final analyses. The severity of neuropathy was scored using the National Cancer Institute Common Toxicity Criteria.
At the screening visit, 90 patients (59%) still reported neuropathic symptoms. Tingling (71%), numbness (58%), impaired sensory function (46%) and pain in hands and feet (40%) were the most common symptoms. The median intensity of neuropathic symptoms was 28/100 on the visual analogue scale. Grade 1 sensory neuropathy was found in 19 out of 90 patients (21%), grade 2 in 38 (42%) and grade 3 in 33 (37%) patients. Grade 1 motor neuropathy was found in 28 (31%), grade 2 in 14 (16%) and grade 3 in one patient (1%). Grade 4 sensory or motor neuropathy was not seen. In the whole cohort of 152 patients, fatigue (66%), mucositis (61%) and neuropathic symptoms (59%) were the most commonly reported symptoms. Every third patient (37%) with neuropathic symptoms ranked them as the most troublesome symptom.
Neuropathy is a common and troublesome adverse effect of chemotherapy, even though the intensity of the symptoms is mild. Thus, the intensity and inconvenience does not correlate to each other.
Supportive Care in Cancer 11/2010; 19(12):1991-6. · 2.09 Impact Factor
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Pain 09/2010; 150(3):375-6. · 5.78 Impact Factor
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New England Journal of Medicine 04/2010; 362(17):1641; author reply 1641-2. · 53.30 Impact Factor
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ABSTRACT: In the absence of external stimuli, human hemodynamic brain activity displays slow intrinsic variations. To find out whether such fluctuations would be altered by persistent pain, we asked 10 patients with unrelenting chronic pain of different etiologies and 10 sex- and age-matched control subjects to rest with eyes open during 3-T functional MRI. Independent component analysis was used to identify functionally coupled brain networks. Time courses of an independent component comprising the insular cortices of both hemispheres showed stronger spectral power at 0.12 to 0.25 Hz in patients than in control subjects, with the largest difference at 0.16 Hz. A similar but weaker effect was seen in the anterior cingulate cortex, whereas activity of the precuneus and early visual cortex, used as a control site, did not differ between the groups. In the patient group, seed point-based correlation analysis revealed altered spatial connectivity between insulae and anterior cingulate cortex. The results imply both temporally and spatially aberrant activity of the affective pain-processing areas in patients suffering from chronic pain. The accentuated 0.12- to 0.25-Hz fluctuations in the patient group might be related to altered activity of the autonomic nervous system.
Proceedings of the National Academy of Sciences 03/2010; 107(14):6493-7. · 9.68 Impact Factor
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ABSTRACT: Recurrent lymphocytic meningitis (RLM) is a rare illness caused mostly by herpes simplex virus type 2 (HSV-2). Predisposing factors are not known. Deficiencies in immunoglobulin (Ig) G subclasses 1 (IgG1) and 3 (IgG3) and complement protein C4 are associated with susceptibility to and persistence of bacterial and viral infections. Selected HLA and mannose-binding lectin (MBL) alleles have previously been associated with recurrent genital herpes or herpetic meningitis. We assessed the frequencies of low IgG1 and IgG3, their allotypes (Gm), and HLA-A*, -B*, -DRB1*, and MBL2 alleles, as well as deficiencies in C4A and C4B genes, as potential predisposing factors for HSV-2-associated RLM. The level of IgG1 was lower (p = 0.009) and the frequency of low IgG1 was higher (p < 0.001) in patients than in controls. Furthermore, the risk for a new meningitis episode was increased in patients with low IgG1 (incident ratio 2.05). HLA-DRB1*01 (p = 0.009) and -B*27 (p = 0.050) were more common among patients than controls. We conclude that HLA-DRB1*01 and -B*27 alleles and low plasma IgG1 levels may be significant risk factors for RLM.
Human immunology 10/2009; 71(2):179-81. · 2.55 Impact Factor
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ABSTRACT: Bodily representations of the primary somatosensory (SI) cortex are constantly modified according to sensory input. Increased input due to training as well as loss of input due to deafferentation are reflected as changes in the extent of cortical representations. Recent studies in complex regional pain syndrome (CRPS) patients have indicated that the chronic pain itself is associated with cortical reorganization. However, it is unclear whether the observed reorganization is specific for CRPS or if it can be detected also in other types of chronic pain. We therefore searched for signs of cortical reorganization in a group of 8 patients who suffered from chronic pain associated with herpes simplex virus infections. The pain was widespread but restricted to unilateral side of the body and included the upper limb. We recorded neuromagnetic responses to tactile stimulation of fingers of both hands in patients and in a group of healthy, matched control subjects. In the patients, the distance between the thumb (D1) and little finger (D5) representations in SI cortex was statistically significantly smaller in the hemisphere contralateral to painful side than in the hemisphere contralateral to healthy side. In the control subjects, the D1-D5 distance was the same in both hemispheres. PERSPECTIVE: The present results indicate that cortical reorganization occurs in chronic neuropathic pain patients even without peripheral nerve damage. It is possible that cortical reorganization is related to chronic pain, regardless of its etiology. Causality between reorganization and chronic pain should be examined further to develop therapeutic approaches for chronic pain.
The journal of pain: official journal of the American Pain Society 09/2009; 10(8):854-9. · 3.78 Impact Factor
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ABSTRACT: We found the prevalence of recurrent lymphocytic meningitis associated with herpes simplex virus type 2 (HSV-2) was 2.2/100,000 population in Finland during 1996-2006, higher than previous estimates. PCR was most sensitive in detecting HSV-2 DNA from cerebrospinal fluid if the sample was taken 2-5 days after symptom onset.
Emerging Infectious Diseases 08/2009; 15(7):1119-22. · 6.79 Impact Factor
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ABSTRACT: Neuropathy is a common adverse effect of chemotherapy. The tricyclic antidepressant, amitriptyline, is a gold standard in the treatment of neuropathic pain. This double-blind, randomized placebo-controlled trial assessed the efficacy of amitriptyline to prevent chemotherapy-induced neuropathic symptoms.
Patients without previous neuropathy, who started chemotherapy with vinca alcaloids, platina derivatives or taxanes, were randomized to receive amitriptyline (target dose, 100 mg daily) or placebo for the duration of their chemotherapy. Chemotherapy-induced neuropathic symptoms were evaluated with a patient diary and after every third chemotherapy cycle with clinical examination. The diary data were transformed to a neuropathy score. A total of 114 patients fulfilling the inclusion criteria were randomly assigned to the treatment or control arm.
There was no difference in the appearance of chemotherapy-induced neuropathic symptoms between the groups. In general, the intensity of neuropathic symptoms was mild.
Amitriptyline does not prevent chemotherapy-induced neuropathy.
Anticancer research 08/2009; 29(7):2601-6. · 1.73 Impact Factor
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ABSTRACT: A recent study described for the first time a patient group that suffered from spontaneous chronic pain and from recurrent herpes simplex virus (HSV) infections. The patients had pain in widespread areas on one side of the body and were--due to subtle immunological abnormalities--susceptible to HSV infections. Although the clinical features of the pain suggested involvement of the central nervous system, supporting evidence for this was lacking. The objective of this study was to search for changes in the central nervous system that could account for the chronic pain in these patients. We monitored the central processing of pain and touch in eight patients and 11 healthy control subjects, who received painful heat and innocuous tactile stimuli to the hands during functional magnetic resonance imaging. Possible changes in the gray matter density of the brain were assessed with voxel-based morphometry. We found functional changes in the patients' central pain circuitry: activation to heat pain was weaker than in control subjects in the insular cortices, anterior cingulate cortex (ACC), and thalamus, while the activations to innocuous tactile stimuli were similar in both groups. Gray matter density was decreased in the patients' frontal and prefrontal cortices and in the ACC. The observed functional and structural changes in the central pain circuitry, together with the clinical features of the chronic pain support the hypothesis for central involvement in the development of chronic pain in these patients.
Pain 06/2009; 144(1-2):200-8. · 5.78 Impact Factor
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ABSTRACT: Fentanyl is an opioid with high lipid solubility, suitable for intravenous, spinal, transmucosal and transdermal administration. The transdermal fentanyl patch has become widely used in the treatment of both malignant and non-malignant chronic pain. The absorption of fentanyl from the patch is governed by the surface area of the patch, by skin permeability and by local blood flow. The aim of this study is to find out whether absorption of fentanyl in cachectic patients with cancer-related pain is different from that of normal weight cancer patients. We recruited ten normal weight (mean body mass index (BMI) 23 kg/m(2)) and ten cachectic (mean BMI 16 kg/m(2)) cancer pain patients. A transdermal fentanyl patch with a dose approximately equianalgesic to the patients' previous opioid dose was administered to the upper arm of the patient for 3 days. Prior to patch application, the height, weight and BMI of the patient, as well as upper arm skin temperature, local sweating, thickness of skin fold and local blood flow were measured. Plasma fentanyl concentrations were analyzed from blood samples taken at baseline, 4, 24, 48 and 72 h. Plasma fentanyl concentrations adjusted to dose were significantly lower at 48 and 72 h in cachectic patients than normal weight patients. The cachectic patients had a significantly thinner upper arm skin fold, but no differences were found in local blood flow, sweating, or skin temperature. Absorption of transdermal fentanyl is impaired in cachectic patients compared with that of normal weight cancer pain patients.
Pain 06/2009; 144(1-2):218-22. · 5.78 Impact Factor
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ABSTRACT: The purpose of the study was to examine the trends in opioid consumption in the five Nordic countries between 2002 and 2006 and to explore possible explanations for changes in the quality and quantity of opioids consumed.
Data on opioid consumption were extracted from the databases of the respective national authorities. Six strong and four weak opioids were included in the analysis. Data were presented as DDDs/1000 inhabitants/day. In addition, information on the reimbursement system and opioid prescription regulations in respective countries was obtained. Also, the cost of analgesic medication in the Nordic countries was compared as equipotent doses of CR morphine, CR oxycodone and transdermal fentanyl.
During the five year period examined the total use of opioids showed some increase in all countries except Sweden. In Finland and Norway the increase in the total consumption was mainly due to an increase in the consumption of strong opioids while in Denmark the rise was due to increased consumption of weak opioids. The consumption of morphine was stabile or decreased slightly in all countries while the use of transdermal fentanyl increased in Denmark, Finland and Sweden and oxycodone in all countries except Iceland. The consumption of dextropropoxyphene decreased in all countries. Reimbursement policies or prescription regulations do not seem to explain the kind/type of opioids consumed or changes in their consumption.
Consumption of opioid analgesics in the Nordic countries showed changes over the five year period that cannot be explained by pharmacology, price, reimbursement or prescription regulations. Marketing has most likely significantly influenced the type and amount of opioids consumed.
European journal of pain (London, England) 01/2009; 13(9):954-62. · 3.37 Impact Factor
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Pain 11/2008; 140(2):247-8. · 5.78 Impact Factor
