Biomedical subjects

E Kalso

Publications and source records attributed to E Kalso.

At least 19 recordsLinked to original sources

PubMed1999

Endogenous noradrenergic tone controls symptoms of allodynia in the spinal nerve ligation model of neuropathic pain.

Endogenous inhibitory controls were studied in the spinal nerve ligation model of neuropathic pain. Atipamezole, a selective alpha2-adrenoceptor antagonist, produced both mechanical and cold allodynia in those rats which had not developed clear neuropathic symptoms. The same doses (50 microg i.t. or 1 mg/kg s.c.) did not increase the severity of symptoms in rats which had developed them. The opioid receptor antagonist naloxone (20 microg i.t. or 1 mg/kg s.c.) had no effect on the neuropathic symptoms. These results indicate that mechanical and cold allodynia are under endogenous noradrenergic rather than opioidergic control in this model of neuropathic pain.

Adrenergic alpha-Antagonists↗

PubMed1999

Pain related undergraduate teaching in medical faculties in Finland.

The present questionnaire study was conducted to examine how teachers in all Finnish medical faculties have included pain teaching in their courses for undergraduate medical students. The study was planned to compare the existing education in Finland with the IASP curriculum on pain for medical schools. In 1991 and 1995 the questionnaire was sent to a total of 135 and 130 university teachers, respectively. The teachers were asked about the quantity and quality of their pain teaching. Teachers' attitudes on pain related teaching were also examined. A Finnish translation of the IASP curriculum was provided, and university teachers were asked to evaluate it and compare it with their current teaching. The educational programs of all universities were also analyzed. After completion of these surveys, representatives of teachers responsible for teaching of pain, and of medical students from all Finnish medical faculties were invited to a meeting to discuss methods for improving and developing education. Completed questionnaires were received from 107 university teachers (78%) in 1991 and from 74 (60%) in 1995. No printed curricula for pain education were found in any university and in all universities pain teaching was provided in an inconsistent way. There were differences, yet statistically non-significant, between the faculties in the pain teaching. No major differences were observed between the two questionnaires. A serious lack of teaching in psychology of pain was a general finding. University teachers were found to have positive attitudes towards developing their teaching of pain. The IASP curriculum has not been fully followed but was considered a valuable tool in planning the educational programs. The curriculum should be distributed directly to the governmental bodies of the universities, since individual university teachers are not necessarily familiar with it. Local associations may have an important role in this distribution as we have shown. This report shows the necessity of changing the attitudes of university teachers providing concrete teaching programs for pain. A multimedia package of pain containing references, video tapes and cd-discs produced by a workshop of IASP would certainly be welcome.

Curriculum↗

PubMed1999

Behavioural measures of depression and anxiety in rats with spinal nerve ligation-induced neuropathy.

The behaviour of rats with spinal nerve ligation-induced neuropathic pain was studied using tests developed to measure depression and anxiety. Adult male Sprague-Dawley rats were tested with the open field test, elevated plus maze, two compartment test and forced swimming test. Spontaneous motility was measured in a photocell observation box. Mechanical sensitivity was tested with von Frey hairs and cold sensitivity with the acetone drop test. The L5-6 spinal nerves were ligated or a sham operation was performed and the rats were followed for 2 weeks before the same set of tests were repeated. Most of the neuropathy operated rats had mechanical and cold allodynia. With post-injury there was a significant decrease in the activity in the open field test and motility box tests, when compared with the pre-injury results. In the elevated plus maze test there was a significant reduction in the motility, but there was no change in the time spent in the closed wings. In the two compartment test there were no significant differences between the pre- and post-injury results. There were no differences between the rats with spinal nerve ligation injury and the sham operated rats in any of the tests. The results were also comparable when rats that developed a high degree of neuropathy were compared with the rats with low degree of neuropathy and the sham operated group. In conclusion, spinal nerve ligation injury of the spinal nerves L5-6 induces mechanical and cold allodynia, but it does not seem to produce general suffering or measurable anxiety to the animals. Furthermore, tests for anxiety and depression were not able to predict which animals were vulnerable to express symptoms of neuropathic pain after nerve injury.

Animals↗

PubMed1999

Chronic pain after thoracic surgery: a follow-up study.

BACKGROUND: The incidence of long-term post-thoracotomy pain is reported to be up to 67%. A relationship between the severity of acute postoperative pain and the development of chronic post-thoracotomy pain has been suggested. METHODS: Patients scheduled for elective thoracotomy were interviewed before and one week after surgery to find out if they had pain before surgery and how much pain they experienced postoperatively. The amount of analgesics the patients were given were registered during the first 5 postoperative days. The patients were interviewed by letter 3, 6 and 12 months after surgery to find out if they still had pain due to surgery and to what extent this pain interfered with their daily activities. RESULTS: One hundred and ten patients entered the study. Information about the complete study period was obtained from 67 patients. The incidence of chronic post-thoracotomy pain was 80% at 3 months, 75% at 6 months and 61% one year after surgery. The incidence of severe pain was 3-5%. Chronic post-thoracotomy pain interfered with the patient's normal daily life in more than half of the patients. High consumption of analgesics during the first postoperative week was associated with a higher risk of chronic post-thoracotomy pain. CONCLUSION: A significant proportion of patients undergoing thoracotomies will suffer from chronic pain. Surgeons and anaesthetists should be aware of this fact and they should look for effective means of preventing and treating this pain syndrome.

Activities of Daily Living↗

PubMed1999

Chronic post-treatment symptoms in patients with breast cancer operated in different surgical units.

AIMS: This study was designed to find out whether women operated in high volume surgical units have less chronic symptoms than women operated in smaller volume units. METHODS: A questionnaire was sent to 265 consecutive women treated at the Department of Oncology, Helsinki University Central Hospital, from January to June 1996. Of the patients, 129 were operated in hospitals experienced in breast cancer surgery (high volume units = HVU) and 92 patients in district hospitals with less experience in breast surgery (low volume units = LVU). RESULTS: Chronic symptoms were less common in HVU than in LVU: chronic pain (56 vs. 43%, P<0.05) or strange sensations (45 vs. 26%, P<0.01) in the ipsilateral arm or phantom sensations in the removed breast (66 vs. 26%, P<0.001). The risk factors included in the multivariate model for chronic pain in the breast area were: intensity of acute post-operative pain, radiotherapy and depression and for the chronic arm pain: low volume unit and depression. CONCLUSIONS: More careful surgical technique seems to reduce the risk of chronic pain following treatment of breast cancer. Chronic pain is associated with more intense post-operative pain and depression.

Adult↗

PubMed1999

I.v. diclofenac and ketorolac for pain after thoracoscopic surgery.

We studied intensity of pain, cumulative morphine consumption, ventilatory and renal function, and haemostasis in patients undergoing video-assisted thoracoscopic surgery and receiving a 2-day i.v. infusion of diclofenac, ketorolac or saline. Plasma concentrations of the two NSAID were also measured. The study was randomized, double-blind and placebo-controlled, with 10 patients in each group. Patients experienced mainly moderate pain. Mean consumption of i.v. morphine during the first day after operation was 57 (SEM 11) mg in the placebo group. Diclofenac and ketorolac were equally effective in reducing total morphine consumption (61% and 52%, respectively). Adverse events were similar and minor. Greater variability in plasma concentrations of ketorolac were detected compared with diclofenac.

Adolescent↗

PubMed1999

Systemic physostigmine shows antiallodynic effects in neuropathic rats.

UNLABELLED: The aim of this study was to examine the antiallodynic and antinociceptive effects of subcutaneously administered physostigmine (50, 100, 200 micrograms/kg), compared with morphine (2.5, 5, 10 mg/kg) and NaCl after spinal nerve ligation in rats. The following stimuli were used: acetone (cold allodynia), von Frey hairs (mechanical allodynia), and paw flick test (thermal nociception). Motility boxes were used to investigate the effects of the drugs on motor performance. Physostigmine attenuated both mechanical and cold allodynia dose-dependently but had no effect on the paw flick test. The effect was antagonized by atropine (muscarinic receptor antagonist) but not by mecamylamine (nicotinic receptor antagonist) or naloxone (opioid receptor antagonist). Morphine produced dose-dependent antiallodynic and antinociceptive effects. In the antiallodynic doses, morphine caused severe rigidity. Physostigmine 200 micrograms/kg impaired locomotor activity, but no rigidity was observed. IMPLICATIONS: Physostigmine has different effects on allodynia and nociception, which suggests that different cholinergic (muscarinic) mechanisms may be involved in neuropathic and nociceptive pain.

Analgesics↗

PubMed1999

Gene for pain modulatory neuropeptide NPFF: induction in spinal cord by noxious stimuli.

Neuropeptides FF (NPFF), AF (NPAF), and SF (NPSF) are homologous amidated peptides that were originally identified on the basis of similarity to the molluscan neuropeptide FMRF-amide. They have been hypothesized to have wide-ranging functions in the mammalian central nervous system, including pain modulation, opiate function, cardiovascular regulation, and neuroendocrine function. We have cloned the NPFF gene from human, bovine, rat, and mouse, and show that the precursor mRNA encodes for all three of the biochemically identified peptides (NPFF, NPAF, and NPSF). We demonstrate that NPFF precursor mRNA expression by Northern analysis and map sites of expression by in situ hybridization. We confirm the validity of the in situ hybridization by showing that its distribution in the brain and spinal cord matches the distribution of NPFF and NPSF immunoreactivity. We go on to show that the mRNA levels (as measured by in situ hybridization) in the spinal cord can be up-regulated by a model for inflammatory pain (carrageenan injection), but not by a model for neuropathic pain (lumbar nerve ligation). Our results confirm the evolutionary conservation of NPFF, NPAF, and NPSF neuropeptide expression in mammalian brain. They also provide a context for the interpretation of the pain-sensitizing effects of injections of these peptides that have been previously reported. Our results support a model for the role of these peptides in pain regulation at the level of the spinal cord.

Amino Acid Sequence↗

PubMed1998

Phantom-limb pain.

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Amputation, Surgical↗

PubMed1998

Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone.

BACKGROUND: Oxycodone is metabolized in the liver by means of O-demethylation to form oxymorphone in a reaction catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). This enzyme is expressed as 2 phenotypes (extensive and poor metabolizers). Several drugs are metabolized by CYP2D6, and clinically relevant drug interactions may occur. The aim of this study was to evaluate the role of oxymorphone in mediating the opioid effects of oxycodone by means of blocking CYP2D6 with quinidine. METHODS: Ten healthy extensive metabolizers were administered 20 mg controlled-release oxycodone after premedication with placebo or 200 mg quinidine in this randomized, double-blind crossover study. A dose of 100 mg quinidine was administered 6 hours later. Plasma opioid concentrations, subjective pharmacodynamic ratings, and psychomotor function were assessed for 24 hours after drug administration. RESULTS: No oxymorphone was detected at any time after quinidine premedication in 8 of 10 subjects. Plasma oxycodone (difference not significant) and noroxycodone (P < .01) concentrations were greater after quinidine pretreatment. Prevention of the production of oxymorphone by quinidine did not affect the psychomotor or subjective drug effects of oxycodone. No difference in number of adverse effects was observed after the 2 pretreatments. CONCLUSIONS: A significant reduction in plasma oxymorphone levels did not substantially alter the pharmacodynamic effects of oxycodone. Analgesia was not evaluated because pain was not present.

Adult↗

PubMed1998

The effects of the alpha2-adrenergic agonist, dexmedetomidine, in the spinal nerve ligation model of neuropathic pain in rats.

UNLABELLED: Peripheral nerve injury may lead to neuropathic pain. Alpha2-adrenergic agonists acting in the descending inhibitory tracts of the spinal cord are effective in acute nociceptive, inflammatory, and, possibly, neuropathic pain. We studied the prevention and treatment of neuropathy with the selective alpha2-adrenergic agonist dexmedetomidine in male Sprague-Dawley rats with unilateral peripheral mononeuropathy resulting from tight ligation of the L5 and L6 spinal nerves. Rats with ligation injury developed mechanical and cold allodynia, but not heat hyperalgesia. Dexmedetomidine (120 microg/kg subcutaneously [S.C.] 30 min before the injury) did not attenuate mechanical or cold allodynia. Dexmedetomidine infusions (60 microg/d for 7 days after the injury, or 30 microg/d for 7 days started 14 days after the injury) did not attenuate mechanical or cold allodynia in the ipsilateral paw, but they increased mechanical allodynia during the latter treatment in the paw contralateral to the injury. Atipamezole (1 mg/kg S.C.) induced mechanical and cold allodynia in rats that had not developed allodynia in 14 days after the injury. In conclusion, although alpha2-adrenergic mechanisms are recognized as important in the development of neuropathic pain-like symptoms in this animal model, we found no favorable effect from systemic treatment with dexmedetomidine at tolerable doses. IMPLICATIONS: We studied the prevention and treatment of nerve injury-induced pain with the alpha2-adrenergic agonist dexmedetomidine in an animal model. At tolerable doses, systemic dexmedetomidine neither prevented nor attenuated neuropathic pain behavior.

Adrenergic alpha-Agonists↗

PubMed1997

Neuropeptide FF in the rat spinal cord during carrageenan inflammation.

The role of neuropeptide FF (NPFF) in the modulation of spinal nociception was studied in rats with carrageenan inflammation in the hind paw. Normally no NPFF-ir neuronal cell bodies are found in the spinal cord. During inflammation NPFF-neurons were seen in an area receiving innervation from the inflamed hind limb, but in rats pretreated with morphine no NPFF-ir neurons were found. NPFF or IgG from NPFF immunoserum administered intrathecally had no effect in thermal and mechanical nociceptive tests. Morphine produced significant antinociception in both tests in the inflamed paw, but the effect was not modified by NPFF. These findings differ from the effects of intrathecal administration of NPFF and opioids in acute thermal tests when no inflammation is present. The role of NPFF in the modulation of nociception in the spinal cord may be markedly changed during acute inflammation.

Animals↗

PubMed1997

Neuropeptide FF-like immunoreactivity in human cerebrospinal fluid of chronic pain patients and healthy controls.

Neuropeptide FF (NPFF) is a neuropeptide with some antiopioid characters found in several mammalian species. In human brain it might be an important pain-regulating peptide. Using a specific and sensitive radioimmunoassay we found a mean concentration of NPFF in human cerebrospinal fluid (CSF) of healthy volunteers of 1.6 +/- 1.1 pg/ml (n = 19) and in chronic pain (CPD) patients of 1.4 +/- 1.2 pg/ml (n = 16). The NPFF concentrations in CSF and plasma did not correlate. There was no difference in the NPFF concentrations in CSF and plasma between CPD patients and healthy controls. NPFF in CPD patients did not correlate significally with any pain characteristic. This study provides evidence for the presence of NPFF in human brain, but does not support the hypothesis that chronic pain is a consequence of elevated production of NPFF.

Adult↗

PubMed1997

Controlled-release oxycodone and morphine in cancer related pain.

Controlled-release (CR) formulations of oxycodone and morphine were compared in 45 patients with chronic cancer pain. The study was started with an open-label, randomised titration phase to achieve stable pain control for at least 48 h, followed by a double-blind, randomised, crossover phase in two periods, 3-6 days each. To blind the study using available tablet strengths, the dose ratio of oxycodone to morphine was set at 2:3. A daily telephone contact was maintained between the patient and the investigator. The patients were asked to assess pain intensity four times a day and acceptability of therapy twice daily, and to record possible adverse effects. Pharmacodynamic evaluations were performed at the end of each double-blind period. The patients were allowed to use escape analgesic (respective opioid as oral solution) as needed. Twenty-seven patients were evaluable for both safety and efficacy. Pain was well-controlled during both stable phases. When the period effect was taken into account the two opioids provided comparable analgesia. If the results of the two periods were combined, the patients consumed significantly more escape doses and the mean pain intensities were significantly greater with CR oxycodone. The total opioid consumption ratio of oxycodone to morphine was 2:3 when oxycodone was administered first, and 3:4 when oxycodone was administered after morphine. The total incidence of adverse experiences reported by the patients was similar, but significantly more vomiting occurred with morphine, whereas constipation was more common with oxycodone.

Adult↗

PubMed1997

Pain relief from intra-articular morphine after knee surgery: a qualitative systematic review.

Reduction of postoperative pain by injecting opioid into the knee joint is believed to support the hypothesis of peripheral opioid receptor activation in inflammation. The study design consisted of a systematic review of randomised controlled trials (RCTs). Main outcomes were pain intensity and the use of supplementary analgesics. Efficacy of intra-articular bupivacaine against placebo was used as an index of internal sensitivity. Evidence of efficacy was sought in both early (0-6 h after intra-articular injection) and late (6-24 h) periods. Thirty-six RCTs in knee surgery were found. Six had both a local anaesthetic control and placebo; four showed internal sensitivity. All four sensitive studies had at least one outcome showing efficacy of intra-articular morphine against placebo. Six studies compared intra-articular morphine with intravenous or intramuscular morphine or with intra-articular saline without a bupivacaine control. Four of the six studies showed greater efficacy for intra-articular morphine. There was no dose-response evident. No quantitative analysis of pooled data was done. We conclude that intra-articular morphine may have some effect in reducing postoperative pain intensity and consumption of analgesics. These studies had significant problems in design, data collection, statistical analysis and reporting. Trials of better methodological quality are needed for a conclusive answer that intra-articular morphine is analgesic, and that any analgesia produced is clinically useful.

Analgesics, Opioid↗

PubMed1997

Pharmacokinetic comparison of intravenous and intranasal administration of oxycodone.

BACKGROUND: For patients with chronic pain, treatment with oral analgesics is considered most convenient and feasible. Sometimes, however, the oral route cannot be used because of difficulties with swallowing, nausea, vomiting and gastrointestinal obstruction. To investigate the applicability of the nasal route for the administration of oxycodone, we studied the intravenous and intranasal pharmacokinetics of oxycodone in healthy volunteers. METHODS: Ten healthy volunteers (3 males and 7 females) were given either an intravenous bolus of oxycodone hydrochloride 0.05 mg/kg or nasal sprays of oxycodone hydrochloride 0.1 mg/kg in a cross-over manner. Blood was sampled and subjective effects and side effects were recorded for 10 h. RESULTS: After intravenous administration of oxycodone, the plasma clearance of oxycodone was 0.83 +/- 0.33 l/min (mean +/- SD) and the volume of distribution at steady-state 2.02 +/- 1.47 l/kg and the terminal elimination half-life 157 +/- 47 min. After intranasal administration, peak plasma concentration of oxycodone was 13 +/- 6 ng/ml and it was reached in the median time of 25 min. The intranasal bioavailability of oxycodone was 0.46 +/- 0.34. No clinically significant changes in blood pressure or heart rate were observed but all subjects experienced somnolence after both modes of administration. CONCLUSIONS: The results of this study show that oxycodone is rapidly and rather effectively absorbed from the nasal mucosa but the interindividual differences are large. The intranasal route may in some cases be an attractive alternative to oral or parenteral administration of opioid analgesics. However, because of large interindividual differences, it is prudent to titrate the dose of intranasal oxycodone individually.

Administration, Intranasal↗

PubMed1997

Intrathecal morphine for post-sternotomy pain in patients with myasthenia gravis: effects on respiratory function.

BACKGROUND: Thymectomy can induce a remission or at least an improvement in myasthenia gravis (MG) patients. After sternotomy MG patients with compromised muscle strength need an excellent postoperative pain relief. This study was designed to evaluate the efficacy of intrathecal morphine (ITM) on ventilatory function among MG patients undergoing trans-sternal thymectomy, when intravenous morphine served as control. METHODS: Twenty consecutive MG patients were randomised to receive either morphine (10 micrograms/kg) intrathecally at induction or intravenous morphine (30 micrograms/kg) with a patient-controlled analgesia (PCA) device. Anaesthesia was standardised. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), respiratory rate, oxygen saturation, arterial blood gases, pain intensity and morphine consumption were assessed during 48 hours. RESULTS: The mean age of the patients was 35 +/- 3.4 years and the mean duration of the disease 1.9 +/- 0.5 years. According to Osserman's classification 70% of the patients belonged to Class IIA and 30% to Class IIB. ITM restored ventilatory function significantly better than iv PCA morphine. FVC recovered to 60% and FEV1 to 57% of the baseline values in the ITM group compared with 32% (P < 0.05) and 37% in the PCA morphine group, respectively. Postpuncture headache occurred in 4/10 patients. CONCLUSION: Intrathecal morphine provided effective postoperative analgesia and significantly improved ventilatory function when compared with intravenous morphine.

Adolescent↗

PubMed1997

Memory for pain.

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Acute Disease↗