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Biomedical subjects

Eija Kalso

Publications and source records attributed to Eija Kalso.

At least 19 recordsLinked to original sources
PubMed2006

The compassionate brain: humans detect intensity of pain from another's face.

Understanding another person's experience draws on "mirroring systems," brain circuitries shared by the subject's own actions/feelings and by similar states observed in others. Lately, also the experience of pain has been shown to activate partly the same brain areas in the subjects' own and in the observer's brain. Recent studies show remarkable overlap between brain areas activated when a subject undergoes painful sensory stimulation and when he/she observes others suffering from pain. Using functional magnetic resonance imaging, we show that not only the presence of pain but also the intensity of the observed pain is encoded in the observer's brain-as occurs during the observer's own pain experience. When subjects observed pain from the faces of chronic pain patients, activations in bilateral anterior insula (AI), left anterior cingulate cortex, and left inferior parietal lobe in the observer's brain correlated with their estimates of the intensity of observed pain. Furthermore, the strengths of activation in the left AI and left inferior frontal gyrus during observation of intensified pain correlated with subjects' self-rated empathy. These findings imply that the intersubjective representation of pain in the human brain is more detailed than has been previously thought.

Adolescent↗
PubMed2006

Acute opioid effects on human brain as revealed by functional magnetic resonance imaging.

Functional magnetic resonance imaging has been widely used to study brain activation induced either by specific sensory stimulation or motor or cognitive task performance. We demonstrate that functional magnetic resonance imaging can provide information of brain regions involved in opioid-induced central nervous system effects. The reproducibility of the responses in the predefined regions of interest was confirmed by repeated boluses of ultra-short acting mu-opioid receptor agonist remifentanil and saline. We report spatially and temporally detailed information after remifentanil administration. Areas rich in mu-opioid receptors showed strong activations, whereas primary somatosensory cortex that has the lowest density of mu-opioid receptors showed negligible activation. The cingulate, orbitofrontal, posterior parietal and insular cortices, and amygdala showed activation, which was temporally closely related to most subjective sensations that were strongest at 80 to 90 s after drug administration. These areas belong to a circuitry that modulates the affective experience of sensory stimuli.

Adult↗
PubMed2006

How palliative care of cancer patients is organised between a university hospital and primary care in Finland.

The aim of this study was to find out how palliative care is organised between the Helsinki University Central Hospital (University Hospital) and primary care. The study consisted of 102 patients whose oncological treatment was terminated and the responsibility of palliative care was transferred to primary care. The patients were interviewed by phone using a structured questionnaire. Another questionnaire form was sent to the primary care physicians. Half of the patients were treated in more than one primary care unit. One third of the outpatients were unaware who was responsible for the care. Most of the patients wanted to be at home but this was achieved in less than half of the cases. Most patients were symptomatic while leaving the University Hospital and no improvement was seen thereafter. Every third patient reported of poor quality of palliative care in the primary care. Also the physicians reported a need for training in palliative care.

Antineoplastic Agents↗
PubMed2006

Successful and unsuccessful outcomes with long-term opioid therapy: a survey of physicians' opinions.

BACKGROUND: The attitudes, beliefs, and experience of physicians will influence how they view the use of opioids for chronic nonterminal pain. OBJECTIVE: To survey pain specialists and primary care providers (PCPs) to obtain their opinion and attitude on aberrant drug-taking behaviors. DESIGN: We surveyed three physician groups, mailing 250 surveys followed by two followups. The survey consisted of (1) questions about beliefs in the effectiveness of long-term opioid therapy and successful and unsuccessful outcomes and (2) a ratings section for possible indicators of unsuccessful long-term opioid treatment. RESULTS: In total 147 questionnaires (82 PCPs, 65 pain specialists) were returned. Pain specialists reported a greater number of patients undergoing long-term opioid therapy compared to nonpain specialists. Opinion regarding the effectiveness of long-term opioid therapy among all physicians was mixed but there was no significant difference between pain specialists and PCPs. There was agreement among physicians with regard to highly aberrant behaviors being indicators of failed long-term opioid therapy. The ratings of the following indicators showed differences between each group: no improvement in pain control, not being able to return to work, and a deterioration in relationships with others. Physicians reported increases or decreases in function to be the most important successful or unsuccessful outcome, respectively. CONCLUSIONS: This preliminary survey showed consensus among physicians that highly aberrant behaviors indicate a failure of chronic opioid therapy. However, when considering less egregious behaviors, it would appear a physician's experience and the number of patients they had taking opioids influenced their opinion.

Analgesics, Opioid↗
PubMed2006

Morphine, oxycodone, methadone and its enantiomers in different models of nociception in the rat.

We studied the effects of the commonly used mu-opioid receptor agonists morphine, oxycodone, methadone and the enantiomers of methadone in thermal and mechanical models of acute pain and in the spinal nerve ligation model of neuropathic pain in rats. Subcutaneous administration of morphine, oxycodone, and methadone produced a dose-dependent antinociceptive effect in the tail flick, hotplate, and paw pressure tests. l-methadone, racemic methadone, and oxycodone had a similar dose-dependent antinociceptive effect, whereas the dose-response curve of morphine was shallower. In the spinal nerve ligation model of neuropathic pain, subcutaneous administration of morphine, oxycodone, methadone and l-methadone had antiallodynic effects in tests of mechanical and cold allodynia. l-methadone showed the strongest antiallodynic effect of the tested drugs. d-methadone was inactive in all tests. Morphine 5.0 mg/kg, oxycodone 2.5 mg/kg, and l-methadone 1.25 mg/kg decreased spontaneous locomotion 30 min after drug administration. In conclusion, in acute nociception all mu-opioid receptor agonists produced antinociception, with morphine showing the weakest effect. In nerve injury pain, l-methadone showed the greatest antiallodynic potency in both mechanical and cold allodynia compared with the other opioids. Opioids seem to have different profiles in different pain models. l-methadone should be studied for neuropathic pain in humans.

Acute Disease↗
PubMed2005

Improving opioid effectiveness: from ideas to evidence.

Opioid effectiveness can be improved by individualizing dosing, route of administration and the drug. Particularly in the treatment of chronic non-cancer pain, careful patient selection is essential. The current review concentrates on new ideas about improving opioid effectiveness by increasing efficacy or reducing adverse effects by combining other drugs that modulate opioid receptor mediated effects. These pharmacological "oipioid adjuvants" include e.g. alpha(2)-adrenergic agonists, non-steroidal anti-flammatory analgesics, NMDA-receptor antagonists, CCK-antagonists, gabapentinoids and NK-1 receptor antagonists. The theoretical background and the clinical evidence of these combinations will be discussed.

Adrenergic alpha-Agonists↗
PubMed2005

Breakthrough pain in malignant and non-malignant diseases: a review of prevalence, characteristics and mechanisms.

Breakthrough pain or transient worsening of pain in patients with an ongoing steady pain is a well known feature in cancer pain patients, but it is also seen in non-malignant pain conditions with involvement of nerves, muscles, bones or viscera. Continuous and intermittent pain seems to be a general feature of these different pain conditions, and this raises the possibility of one or several common mechanisms underlying breakthrough pain in malignant and non-malignant disorders. Although the mechanisms of spontaneous ongoing pain and intermittent flares of pain (BTP) may be difficult to separate, we suggest that peripheral and/or central sensitization (hyperexcitability) may play a major role in many causes of BTP. Mechanical stimuli (e.g. micro-fractures) changes in chemical environments and release of tumour growth factors may initiate sensitization both peripherally and centrally. It is suggested that sensitization could be the common denominator of BTP in malignant and non-malignant pain.

Humans↗
PubMed2005

Oxycodone.

Oxycodone has been in clinical use since 1917. Parenteral oxycodone was used mainly for the treatment of acute postoperative pain whereas combinations, for example, oxycodone and acetaminophen, were used for moderate pain. Since the introduction of controlled-release oxycodone, it has been used to manage cancer-related pain and chronic non-cancer-related pain problems. Controlled studies have been performed in postoperative pain, cancer pain, osteoarthritis-related pain, and neuropathic pain due to postherpetic neuralgia and diabetic neuropathy. The pharmacodynamic effects of oxycodone are typical of a mu-opioid agonist. Oxycodone closely resembles morphine but it has some distinct differences, particularly in its pharmacokinetic profile. Being an old drug, the basic pharmacology of oxycodone has been a neglected field of research.

Analgesics, Opioid↗
PubMed2005

A systematic review of trial methodology, using the placebo groups of randomized controlled trials in paediatric postoperative pain.

Trial methodology was evaluated in paediatric analgesic studies. Databases were searched for randomised, placebo controlled studies of systemic paracetamol, NSAIDs and opioids administered for acute postoperative pain in children. Eighty-three studies met the inclusion criteria and 40 were included for the analysis. Analgesics were administered for established postoperative pain in two studies only. In all other studies they were administered in a prophylactic manner. As study design and sensitivity are particularly demanding in studies using pre-emptive dosing of analgesics, the placebo groups were analysed for issues of study sensitivity. Postoperative pain outcomes included pain scores in 34, rescue analgesia in 36, time to first rescue analgesia in 15, pain on activity in eight, number of patients with pain in six, pain relief in three, global efficacy rating in two and analgesic consumption via PCA in four studies. Twenty of 36 studies reported criteria for rescue analgesia that varied from 20 to 77% of the maximum pain intensity. Need of rescue analgesia showed more often differences between study groups than time to first rescue analgesia or pain intensity. Rescue analgesia was administered to 21-100% of the patients in the placebo groups where no other analgesics were given perioperatively. Most patients in the placebo groups had pain that was greater than 30% of the maximum. In conclusion, analysis of the methodology showed several aspects of trial design that can be improved in future studies. Placebo control groups can be used in paediatric analgesic studies to demonstrate internal sensitivity.

Analgesia, Patient-Controlled↗
PubMed2005

Do strong opioids have a role in the early management of back pain? Recommendations from a European expert panel.

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

Analgesics, Opioid↗
PubMed2005

Sodium channel blockers in neuropathic pain.

Subtypes of tetrodotoxin resistant voltage-gated sodium channels are involved in the development of certain types of neuropathic pains. After nerve injury hyperexcitability and spontaneous firing develop at the site of injury and also in the dorsal root ganglion cell bodies. This hyperexcitability results at least partly from accumulation of sodium channels at the site of injury. The facts that these sodium channels seem to exist in peripheral nerves only and that they can be blocked at the resting state (use-dependent block) offer the possibility to develop drugs, which selectively block these damaged, overexcited nerves. At the moment no such drugs are available. However, some of the most potent drugs that are currently used to manage neuropathic pain e.g. amitriptyline and other tricyclic antidepressants, also block these channels in addition to having several other mechanisms of action. Also most anticonvulsants that are used to alleviate neuropathic pain are sodium channel blockers. Lidocaine, the prototype drug, has been shown to be effective in peripheral neuropathic pain. Its use is limited by the fact that it cannot be administered orally. An oral local anesthetic type sodium channel blocker, mexiletine is an antiarrhythmic agent that is effective in neuropathic pain. However, effective doses may be difficult to achieve because of adverse effects.

Anesthetics, Local↗
PubMed2004

Pain- and morphine-associated transcriptional regulation of neuropeptide FF and the G-protein-coupled NPFF2 receptor gene.

Neuropeptide FF (NPFF) is involved in pain modulation, especially plasticity during inflammatory and neuropathic pain, and opiate interactions. Its nociceptive functions may be mediated by the NPFF2 receptor. To elucidate the role of the NPFF system in plasticity associated with pathologic pain, we studied the changes of NPFF mRNA and NPFF2 receptor mRNA in rat models of acute colonic inflammation, inflammatory pain, and neuropathic pain. Furthermore, we studied the mRNA levels of both NPFF and NPFF2 receptor in morphine-tolerant rats and after acute morphine injections. We found an activation of spinal NPFF and NPFF2 receptor during early inflammatory pain. Supraspinally, we found an up-regulation of NPFF2 receptor mRNA during acute colonic inflammation and neuropathic pain. Acute, but not chronic, morphine activated the genes supraspinally. The results give further evidence for the involvement of the NPFF system in pain modulation and may provide new therapeutic opportunities for pathologic pain.

Animals↗
PubMed2004

Prolactin-releasing peptide affects pain, allodynia and autonomic reflexes through medullary mechanisms.

Prolactin-releasing peptide (PrRP) and neuropeptide FF (NPFF) are RF-amide peptides expressed in brain areas involved in pain modulation. NPFF displays multiple effects on acute, inflammatory and neuropathic pain. The potential role of PrRP in pain was addressed by intrathecal and intracerebral injections of PrRP on pain-related responses in both neuropathic and normal rats. Particularly in the dorsal medulla, PrRP produced significant antinociception in normal rats and an antiallodynic effect in neuropathic rats. To understand the basis of PrRP-induced pain modulation, distributions of PrRP, PrRP receptor, and NPFF were compared in the rat central nervous system. PrRP and NPFF mRNA were expressed in different parts of the nucleus of the solitary tract. In the medulla, PrRP receptor mRNA expression was abundant only in area postrema. Of the peptides studied, only NPFF mRNA was found in the dorsal horn of the spinal cord and spinal nucleus of the trigeminal nerve. PrRP-immunoreactivity corresponded to the mRNA distribution. Even if the neuronal groups producing NPFF and PrRP were distinct, the fiber networks immunoreactive for PrRP and NPFF overlapped. The results show that PrRP modulates nociception due to supraspinal rather than spinal action, and that its antinociceptive mechanism differs from that previously characterized for NPFF.

Animals↗
PubMed2004

Opioids in chronic non-cancer pain: systematic review of efficacy and safety.

Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo in chronic non-cancer pain. Double-blind studies reporting on pain intensity outcomes using validated pain scales were included. Fifteen randomised placebo-controlled trials were included. Four investigations with 120 patients studied intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids with placebo for four days to eight weeks. Six of the 15 included trials had an open label follow-up of 6-24 months. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. About 80% of patients experienced at least one adverse event, with constipation (41%), nausea (32%) and somnolence (29%) being most common. Only 44% of 388 patients on open label treatments were still on opioids after therapy for between 7 and 24 months. The short-term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions. However, only a minority of patients in these studies went on to long-term management with opioids. The small number of selected patients and the short follow-ups do not allow conclusions concerning problems such as tolerance and addiction.

Analgesics, Opioid↗