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Biomedical subjects

E Kalso

Publications and source records attributed to E Kalso.

At least 19 recordsLinked to original sources
PubMed2003

Ketamine as an adjuvant to opioids for cancer pain.

BACKGROUND: Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of cancer pain, particularly when opioids alone prove to be ineffective. Ketamine is known to have hallucinogenic side effects. To date no systematic review of the benefits and harms of adjuvant ketamine for cancer pain has been undertaken. OBJECTIVES: To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids in the treatment of cancer pain. SEARCH STRATEGY: Studies were identified from MEDLINE (1966-2001), EMBASE (1980-2001), CancerLit (1966-2001), the Cochrane Library (Issue 1, 2001); by handsearching reference lists from review articles, trials, and chapters from standard textbooks on pain and palliative care. The manufacturer of ketamine (Pfizer Parke-Davis) provided search results from their in-house database, PARDLARS. SELECTION CRITERIA: RCTs of adult patients with cancer and pain being treated with an opioid, and receiving either ketamine (any dose and any route of administration) or placebo or an active control. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified four RCTs for possible inclusion in the review, and 32 case studies/case series reports. Quality and validity assessment was performed by three independent reviewers, and two RCTs were excluded because of inappropriate study design. Patient reported pain intensity and pain relief was assessed using visual analog scales, verbal rating scales or other validated scales, and adverse effects data were collated. MAIN RESULTS: Two trials were eligible for inclusion in the review and both concluded that ketamine improves the effectiveness of morphine in the treatment of cancer pain. However, pooling of the data was not appropriate because of the small total number of patients (30), and the presence of clinical heterogeneity. Some patients experienced hallucinations on both ketamine plus morphine and morphine alone and were treated successfully with diazepam. No other serious adverse effects were reported. REVIEWER'S CONCLUSIONS: Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of cancer pain. More randomized controlled trials are needed.

Adult↗
PubMed2003

Radiofrequency denervation for neck and back pain. A systematic review of randomized controlled trials.

BACKGROUND: The diagnosis of cervical or lumbar zygapophyseal joint pain can only be made by using local anesthesia to block the nerves supplying the painful joint. There is a lack of effective treatment for chronic zygapophyseal joint pain or discogenic pain. Radiofrequency denervation appears to be an emerging technology, with substantial variation in its use between countries. OBJECTIVES: To assess the effectiveness of radiofrequency denervation for the treatment of musculoskeletal pain disorders. SEARCH STRATEGY: We searched MEDLINE, PsycLIT, and EMBASE from start to February 2002, plus the Cochrane Library 2002, Issue 2. The references of identified articles were checked and three experts in the field of radiofrequency treatment were consulted to identify studies we might have missed. SELECTION CRITERIA: Randomized controlled trials (RCTs) of radiofrequency denervation for musculoskeletal pain disorders, with no language or date restrictions. DATA COLLECTION AND ANALYSIS: Two reviewers selected RCTs that met predefined inclusion criteria, extracted the data, and assessed the main results and methodological quality of the selected trials, using standardized forms. Qualitative analysis was conducted to evaluate the level of scientific evidence. MAIN RESULTS: We found only nine articles, reporting on seven relevant RCTs. Six of the seven were considered to be high-quality. The selected trials included 275 randomized patients, 141 of whom received active treatment. One study examined cervical zygapophyseal joint pain, two cervicobrachial pain, three lumbar zygapophyseal joint pain, and one discogenic low-back pain. The study sample sizes were small, follow-up times short, and there were some deficiencies in patient selection, outcome assessments, and statistical analyses. The level of scientific evidence for the short-term effectiveness of radiofrequency denervation was limited for cervical zygapophyseal joint and cervicobrachial pain, and conflicting for lumbar zygapophyseal joint pain. There was limited evidence suggesting that intradiscal radiofrequency thermocoagulation was not effective for discogenic low-back pain. REVIEWER'S CONCLUSIONS: The selected trials provide limited evidence that radiofrequency denervation offers short-term relief for chronic neck pain of zygapophyseal joint origin and for chronic cervicobrachial pain; conflicting evidence on the short-term effect of radiofrequency lesioning on pain and disability in chronic low-back pain of zygapophyseal joint origin; and limited evidence that intradiscal radiofrequency thermocoagulation is not effective for chronic discogenic low-back pain. There is a need for further high-quality RCTs with larger patient samples and data on long-term effects, for which current evidence is inconclusive. Furthermore, RCTs are needed in non-spinal indications where radiofrequency denervation is currently used without any scientific evidence.

Back Pain↗
PubMed2003

Post-thoracotomy pain after thoracic epidural analgesia: a prospective follow-up study.

BACKGROUND: Pain becomes chronic in 22-67% of patients who undergo a thoracotomy. Thoracic epidural analgesia (TEA) has replaced less invasive methods to manage postoperative pain. We wanted to find out if active use of TEA, combined with extended pain management at home, reduces the incidence of chronic post-thoracotomy pain. METHODS: All consecutive thoracotomy patients during a 16-month period were included. On the ward, pain was measured daily by VAS during rest and coughing and the consumption of analgesics was registered. The patients were interviewed one week after discharge by telephone and by a questionnaire after 3 and 6 months to find out how much pain they had. RESULTS: A total of 114 patients were recruited. The data were analysed from 89 patients who had had TEA and 22 who had had other methods. TEA was effective in alleviating pain at rest and during coughing. In the TEA patients the incidence of chronic pain of at least moderate severity was 11% and 12% at 3 and 6 months, respectively. One week after discharge 92% of all patients needed daily pain medication. CONCLUSIONS: TEA seems effective in controlling evoked postoperative pain, but technical problems occurred in 24% of the epidural catheters. The incidence of chronic pain was lower compared with previous studies where TEA was not used. The patients had significant pain and needed regular pain medication and instructions during the first week after discharge. Extended postoperative analgesia up to the first week at home is warranted.

Adult↗
PubMed2003

Effects of intrathecally administered dexmedetomidine, MPV-2426 and tizanidine on EMG in rats.

BACKGROUND: When administered intrathecally, alpha-2 adrenergic agonists produce spinally mediated antinociception, but also rapidly redistribute to supraspinal sites. This investigation the compared EMG effects of intrathecally administered dexmedetomidine, MPV-2426 (fadolmidine), and tizanidine in Sprague-Dawley rats, which has not been previously described. METHODS: We studied electromyographic (EMG) responses of the head and gastrocnemius muscles, antinociception using the tail-flick test, and sedation by using observer assessment. Saline, dexmedetomidine (0.5 microg, 2.5 microg and 12.5 microg), MPV-2426 (2 microg, 10 microg and 50 microg) and tizanidine (2 microg, 10 microg and 50 microg) were administered intrathecally. RESULTS: Tizanidine 50 microg, MPV-2426 10 microg and 50 microg, and dexmedetomidine 2.5 microg and 12.5 microg, decreased EMG activity (P < 0.005). Dexmedetomidine 12.5 microg, MPV-2426 50 microg, and tizanidine 10 microg and 50 microg increased tail-flick latencies (P < 0.01). Dexmedetomidine alone significantly increased the magnitude of observer-assessed sedation (P < 0.0001). CONCLUSION: We conclude that in rats, intrathecally administered dexmedetomidine, MPV-2426 and tizanidine have dose-dependent effects on EMG. At antinociceptive doses, the EMG effects of these three alpha-2 adrenergic agonists differ (dexmedetomidine > MPV-2426 > tizanidine).

Adrenergic alpha-Agonists↗
PubMed2001

Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain.

OBJECTIVES: To compare patients' preference for transdermal fentanyl or sustained release oral morphine, their level of pain control, and their quality of life after treatment. DESIGN: Randomised, multicentre, international, open label, crossover trial. SETTING: 35 centres in Belgium, Canada, Denmark, Finland, the United Kingdom, the Netherlands, and South Africa. PARTICIPANTS: 256 patients (aged 26-82 years) with chronic non-cancer pain who had been treated with opioids. MAIN OUTCOME MEASURES: Patients' preference for transdermal fentanyl or sustained release oral morphine, pain control, quality of life, and safety assessments. RESULTS: Of 212 patients, 138 (65%) preferred transdermal fentanyl, whereas 59 (28%) preferred sustained release oral morphine and 15 (7%) expressed no preference. Better pain relief was the main reason for preference for fentanyl given by 35% of patients. More patients considered pain control as being "good" or "very good" with fentanyl than with morphine (35% v 23%, P=0.002). These results were reflected in both patients' and investigators' opinions on the global efficacy of transdermal fentanyl. Patients receiving fentanyl had on average higher quality of life scores than those receiving morphine. The incidence of adverse events was similar in both treatment groups; however, more patients experienced constipation with morphine than with fentanyl (48% v 29%, P<0.001). Overall, 41% of patients experienced mild or moderate cutaneous problems associated with wearing the transdermal fentanyl patch, and more patients withdrew because of adverse events during treatment with fentanyl than with morphine (10% v 5%). However, within the subgroup of patients naive to both fentanyl and morphine, similar numbers of patients withdrew owing to adverse effects (11% v 10%, respectively). CONCLUSION: Transdermal fentanyl was preferred to sustained release oral morphine by patients with chronic non-cancer pain previously treated with opioids. The main reason for preference was better pain relief, achieved with less constipation and an enhanced quality of life.

Administration, Cutaneous↗
PubMed2001

Morphine and alternative opioids in cancer pain: the EAPC recommendations.

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated.

Administration, Oral↗
PubMed2001

Role of the delta-opioid receptor in (1DMe)NPYF mediated antinociception.

A selective delta-opioid antagonist, naltrindole, was used to study the role of the delta-opioid receptor in the antinociceptive actions of a synthetic NPFF analog, (1DMe)NPYF. I.t. (1DMe)NPYF (5 nmol) produced antinociception in the tail flick test and (1DMe)NPYF (0.5 nmol) potentiated the antinociceptive effect of i.t. morphine 7.8 nmol. (1DMe)NPYF (5 nmol) had an antihyperalgesic effect in carrageenan inflammation and it significantly reduced mechanical allodynia in the spinal nerve ligation model. All these effects were prevented or significantly reduced by pretreatment with naltrindole (28 nmol) (P < 0.01-0.001). These data suggest that activation of spinal delta-opioid receptors plays an important role in mediating the spinal antinociceptive effects of (1DMe)NPYF.

Analgesics↗
PubMed2001

Chronic post-sternotomy pain.

BACKGROUND: Chronic postoperative pain is a well-recognised problem. The incidence of severe incapacitating pain is about 3-5% after various types of surgery such as thoracotomy, repair of inguinal hernias and mastectomy. Sternotomy causes considerable postoperative pain and patients with chronic post-sternotomy pain are often referred to pain clinics. Epidemiological studies on chronic post-sternotomy pain are scarce, however. The aim of this paper was to study the incidence and possible risk factors of chronic pain following sternotomy operations performed for coronary bypass grafting or thymectomy. METHODS: Two groups of patients were studied for persistent pain following sternotomy operations. A questionnaire was sent in January 1997 to 71 patients with myasthenia gravis (MG) who had undergone a thymectomy during 1985-1996 and 720 patients who had had coronary bypass grafting (CABG) in 1994 were interviewed by letter. The patients were asked about the presence of pain and other symptoms in the chest, shoulders, arms or legs that they thought were connected to surgery. They were also asked about the quality of the pain and its evolvement with time. The patients' records were checked for details about surgery, anaesthesia and the state of the coronary disease. RESULTS: The response rate was 87%. The interval between the interview and surgery varied from 6 months to 12 years in the MG group and it was 2-3 years in the CABG group. In the MG group, 27% of the patients reported chronic post-sternotomy pain, which was moderate to severe in 48% of the patients. In the CABG group, 28% of the patients still had post-sternotomy pain, which was moderate to severe in 38% of patients. Of the patients who had post-sternotomy pain, one-third reported sleep disturbances due to the pain. CONCLUSION: Chronic post-sternotomy pain is an important complication that may have a significant impact on the patient's everyday life. Future studies will show whether minimising complications, improving postoperative care and starting early adequate pain management will reduce the incidence of this problem.

Adolescent↗
PubMed2001

Disodium clodronate in the treatment of diffuse sclerosing osteomyelitis (DSO) of the mandible.

Diffuse sclerosing osteomyelitis (DSO) of the mandible is a chronic condition, the cause of which is not known. Jaw pain, occurring irregularly, is a typical symptom. The aim of the study was to assess the effectiveness of disodium clodronate for relieving pain in patients with DSO. Disodium clodronate is a bisphosphonate used to treat diseases of bone and calcium metabolism. Ten DSO patients experiencing pain received disodium clodronate or placebo intravenously on a randomized double-blind basis. Both minimum (300 mg) and maximum (900 mg) doses were well tolerated. Disodium clodronate administration did not result in better immediate pain relief than placebo administration. However, 6 months after treatment there was a statistically significant difference in pain intensity between the groups, with the disodium clodronate group experiencing significantly less pain.

Adult↗
PubMed2000

Methadone, ciprofloxacin, and adverse drug reactions.

Ciprofloxacin, given to a patient successfully treated with methadone for more than 6 years, caused profound sedation, confusion, and respiratory depression. We suggest that this was caused by ciprofloxacin inhibition of CYP1A2 and CYP3A4 activity, two of the cytochrome p450 isozymes involved in the metabolism of methadone.

Adult↗
PubMed2000

The dissociation of sedative from spinal antinociceptive effects following administration of a novel alpha-2-adrenoceptor agonist, MPV-2426, in the locus coeruleus in the rat.

BACKGROUND: MPV-2426 is a novel alpha-2-adrenoceptor agonist developed for spinal pain therapy. In the present study we characterized its sedative and antinociceptive properties following microinjections into the brainstem and intrathecally at the lumbar spinal cord level. METHODS: Sedative effects of MPV-2426 were assessed in a locomotion measuring device following unilateral microinjection into the locus coeruleus (LC) of the brainstem or 1-2 mm rostral to the LC in rats. Antinociceptive effects induced by MPV-2426 in the brainstem, and for comparison intrathecally at the lumbar spinal cord level, were determined with a tail-flick test. Dexmedetomidine was used as the reference alpha-2-adrenoceptor agonist. RESULTS: MPV-2426 produced a dose-related hypolocomotive/sedative effect, which was significantly stronger following microinjection into the LC than 1-2 mm rostral to the LC. The sedation induced by MPV-2426 was reversed by atipamezole (1 mg/kg s.c.), an alpha-2-adrenoceptor antagonist. The sedative potency of dexmedetomidine, the reference alpha-2-adrenoceptor agonist, was stronger and less dependent on the exact injection site in the brainstem. Following microinjections at sedative doses in the brainstem, only dexmedetomidine produced a significant antinociceptive effect in the tail-flick test. When microinjected into the lumbar spinal cord, MPV-2426 and dexmedetomidine had an equally strong antinociceptive effect in the tail-flick test. CONCLUSION: The results indicate that the sedative potency of MPV-2426 is considerably weaker than that of dexmedetomidine. Additionally, the spread of MPV-2426 within the central nervous system is more limited than that of dexmedetomidine. This could explain why MPV-2426 is sedative only when injected into the LC while antinociceptive effect is obtained when it is injected intrathecally at the lumbar spinal cord level.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2000

Effects of radolmidine, a novel alpha2 -adrenergic agonist compared with dexmedetomidine in different pain models in the rat.

BACKGROUND: Intrathecally administered alpha2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Radolmidine is a novel alpha2-adrenoceptor agonist with a different pharmacokinetic profile compared with the well-researched dexmedetomidine. This study determined the antinociceptive and sedative effects of radolmidine in different models of acute and chronic pain. Dexmedetomidine and saline served as controls. METHODS: Male Sprague-Dawley rats were studied in acute pain (tail flick), carrageenan inflammation, and the spinal nerve ligation model of neuropathic pain. Mechanical allodynia was assessed with von Frey filaments, cold allodynia with the acetone test, and thermal hyperalgesia with the paw flick test. Locomotor activity-vigilance was assessed in a dark field. Dexmedetomidine and radolmidine were administered intrathecally in doses of 0.25 microg, 2.5 microg, 5 microg, and 10 microg. RESULTS: In the tail flick test, radolmidine showed a dose-dependent antinociceptive effect, being equipotent compared with dexmedetomidine. In carrageenan inflammation, intrathecal doses of 2.5 microg or 5 microg of dexmedetomidine/radolmidine produced significant antinociception compared with saline (P < 0.01). The two drugs were equianalgesic. In the neuropathic pain model, an intrathecal dose of 5 microg dexmedetomidine-radolmidine had a significant antiallodynic effect compared with saline (P < 0.01). The two drugs were equipotent. Intrathecal administration of both dexmedetomidine and radolmidine dose dependently decreased spontaneous locomotor acitivity-vigilance, but this effect was significantly smaller after intrathecal administration of radolmidine than after intrathecal dexmedetomidine. CONCLUSIONS: Radolmidine and dexmedetomidine had equipotent antinociceptive effects in all tests studied. However, radolmidine caused significantly less sedation than dexmedetomidine, probably because of a different pharmacokinetic profile.

Adrenergic alpha-Agonists↗
PubMed1999

Neuropeptide FF and modulation of pain.

Neuropeptide FF (NPFF) and the related longer peptide neuropeptide AF (NPAF) derive from a single gene in several mammalian species. The gene product is expressed mainly in the CNS, where the posterior pituitary and dorsal spinal cord contain the highest concentrations. Evidence from biochemical and immunohistochemical studies combined with in situ hybridization using NPFF gene-specific probes suggest that all NPFF-like peptides may not derive from the characterized NPFF gene, but that other genes can exist which give rise to related peptides. Intraventricular NPFF exerts antiopioid effects, but intrathecal NPFF potentiates the analgesic effects of morphine. NPFF mRNA expression is upregulated in the dorsal horn of the spinal cord after carrageenan-induced inflammation in the hind paw of the rat, but not in the neuropathic pain model induced by ligation of the spinal roots. NPFF produces a submodality-selective potentiation of the antinociceptive effect induced by brain stem stimulation in the spinal cord during inflammation, and this effect is independent of naloxone-sensitive opioid receptors. In neuropathic animals, NPFF injected into the periaqueductal grey produces a significant attenuation of tactile allodynia, which is not modulated by naloxone. NPFF thus modulates pain sensation and morphine analgesia under normal and pathological conditions through both spinal and brain mechanisms.

Animals↗
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↗