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Biomedical subjects

O B Fasmer

Publications and source records attributed to O B Fasmer.

At least 19 recordsLinked to original sources

Migraine with and without aura: association with depression and anxiety disorder in a population-based study. The HUNT Study.

Some data indicate that migraine with aura (MA) is more strongly associated with anxiety disorder and depression than migraine without aura (MoA), but the evidence is not conclusive. In the Nord-Trøndelag Health study 1995-1997, a total of 49 205 (75% of the participants) subjects gave valid answers to both HADS (Hospital Anxiety and Depression Scale) and a validated headache questionnaire. Associations between anxiety disorder/depression and MA/MoA were evaluated by multiple logistic regression analysis. Depression (DEP) [odds ratio (OR) 1.7; 95% confidence interval (CI) 1.2, 2.6] and depression with comorbid anxiety disorder (COM) (OR 1.6; 95% CI 1.2, 2.1) were more likely in women having MA than in those with MoA. No stronger association was found for pure anxiety disorder (ANX) in MA vs. MoA (OR 0.9; 95% CI 0.7, 1.5). Among men, we found no difference in prevalence of depression and anxiety disorders between MA and MoA. This is a new finding that might have relevance for both research and clinical treatment.

Adult↗

The prevalence of migraine in patients with bipolar and unipolar affective disorders.

There is a well-known association between migraine and affective disorders, but the information is sparse concerning the prevalence of migraine in subgroups of the affective disorders. The present study was undertaken to investigate the prevalence of migraine in unipolar depressive, bipolar I and bipolar II disorders. Patients with major affective disorders (n = 62), consecutively admitted to an open psychiatric ward, were examined with a semi-structured interview based on DSM-IV diagnostic criteria, combined with separate criteria for affective temperaments. Diagnosis of unipolar and bipolar I disorders followed the DSM-IV criteria, while bipolar II disorder encompassed patients with either discrete hypomanic episodes or a cyclothymic temperament. Migraine was diagnosed according to IHS-criteria. Symptoms of migraine were found to be common in these patients, both in those with unipolar depression (46% prevalence of migraine) and in those with bipolar disorders (44% prevalence). Among the bipolar patients there was, however, a striking difference between the two diagnostic subgroups, with a prevalence of 77% in the bipolar II group compared with 14% in the bipolar I group (P = 0.001). These results support the contention that bipolar I and II are biologically separate disorders and point to the possibility of using the association of bipolar II disorder with migraine to study both the pathophysiology and the genetics of this affective disorder.

Adult↗

Clinical characteristics of patients with major affective disorders and comorbid migraine.

The present study was undertaken to examine the clinical characteristics of patients with major affective disorders and comorbid migraine. Patients (n = 102) with an index episode of either major depression or mania were interviewed with a semi-structured interview based partly on DSM-IV criteria and partly on Akiskal's criteria for affective temperaments. Compared to the patients without migraine (n = 49), the patients with comorbid migraine (n = 53) had a higher frequency of bipolar II disorder (43% vs. 10%), a lower frequency of bipolar I disorder (11% vs. 33%), an approximately equal frequency of unipolar depressive disorder (45% vs. 57%) and a higher frequency of affective temperaments (45% vs. 22%). The migraine patients also had a greater number of anxiety disorders (3.0 vs. 1.9) and a higher frequency of panic disorder and agoraphobia. Gender distribution, age, age at onset of first affective episode, number of previous episodes and symptoms during depressive episodes were similar in both groups. Based on these findings it is suggested that the presence of migraine may be used to delineate a distinct subgroup of the major affective disorders.

Adolescent↗

[Do antidepressive agents have analgesic effects?].

Patients with chronic pain are often depressed, and antidepressants have been widely used in the treatment of these patients. Well controlled clinical studies have shown that antidepressants have analgesic effects, apparently independent of changes in mood, and in lower doses than used in the treatment of depression. Good results have been reported for several types of chronic pain, especially headache and facial pain, arthritis, fibromyalgia and neuralgias. In addition, antidepressants have also an indirect analgesic action by relieving a depressive condition associated with chronic pain.

Analgesics↗

Antinociceptive effects of serotonergic reuptake inhibitors in mice.

The antinociceptive effects of three predominantly serotonergic reuptake inhibitors, alaproclate, citalopram and clomipramine, were examined in mice using the hot-plate, formalin and substance P tests. The effects were compared with those of the noradrenergic reuptake inhibitor, desipramine. Different profiles in the three nociceptive tests were found for all four drugs, using doses of 10 and 40 mg/kg. The selective serotonergic reuptake inhibitor, alaproclate, seemed to have the least antinociceptive effects, and was the only drug that was ineffective in the hot-plate test. The other selective drug, citalopram, had a stronger effect than alaproclate in the substance P test, but in the formalin test, both drugs were approximately equally effective. Clomipramine differed from citalopram by being more effective in the formalin test. These findings thus indicate that selective inhibitors of the uptake of 5-HT have weaker antinociceptive effects than less selective drugs. Desipramine seemed to be no less effective than the serotonergic drugs and was the most potent drug in the hot-plate test.

Alanine↗

Involvement of central serotonergic pathways in nefopam-induced antinociception.

The possible involvement of central serotonergic pathways in the mechanism of action of nefopam was investigated in male albino mice. Nefopam (15 mg/kg i.p.) did not alter the concentration of serotonin or its metabolite 5-hydroxyindole acetic acid in frontal cortex or spinal cord. Lesions of the ascending serotonergic pathways were made by systemic administration of p-chloroamphetamine (PCA). Serotonin depletion in all serotonergic systems was obtained by means of p-chlorophenylalanine (PCPA). Two different nociceptive assays were used, the formalin test and the increasing temperature hot plate test. PCPA pretreatment significantly reduced the effect of nefopam (15 mg/kg) in the formalin test. In contrast, nefopam-induced analgesia was not affected by PCA pretreatment, either in the formalin test or in the increasing temperature hot plate test. In conclusion, the data suggest that descending serotonergic pathways are involved in nefopam-induced antinociception.

Analgesics↗

Increased sensitivity to intrathecal substance P following chronic administration of zimelidine.

The behavioural response to intrathecal substance P (SP) was evaluated following acute and chronic administration of the selective serotonin reuptake inhibitor zimelidine. A single dose of zimelidine (10 mg/kg) attenuated the response to SP by approximately 40%, in agreement with previous findings that acute administration of zimelidine reduces nociceptive behaviour. Twenty-four hours following the withdrawal of long-term treatment with zimelidine (10 mg/kg X 2 daily for 14 days) the behavioural response to SP was increased by 116%. This may indicate the development of supersensitivity to SP, or may reflect an increased responsiveness to noxious stimuli due to reduced serotonergic inhibition.

Animals↗

Development of tolerance to the antinociceptive effect of metergoline.

Metergoline given IP reduced the response to noxious stimulation in the mouse formalin test. Tolerance to this effect developed after a chronic treatment schedule consisting of ten daily injections of 5 mg/kg. Twenty four hours after the last injection a test dose of metergoline (2.5 mg/kg) reduced the licking time in the formalin test by 28% in the chronic metergoline group, compared to 68% reduction in the vehicle-treated animals. In addition, the antinociceptive effect of the 5-hydroxytryptamine releasing compound p-chloramphetamine (PCA) was reduced following chronic treatment with metergoline. The reduced effect of PCA may have been caused by down-regulation of 5-HT2 receptors. However, this finding is also compatible with the contention that metergoline may act as an agonist at postsynaptic serotonergic receptors.

Animals↗

Changes in nociception after acute and chronic administration of zimelidine: different effects in the formalin test and the substance P behavioural assay.

The selective inhibitor of the reuptake of 5-hydroxytryptamine (5-HT), zimelidine, was administered intraperitoneally to mice (10 mg/kg) and nociceptive sensitivity was evaluated using the formalin test (20 microliters of 1% formalin, injected subcutaneously) and the assay for substance P (5 ng administered intrathecally). Zimelidine increased the behavioural response to formalin, but reduced the response to substance P. These effects of zimelidine seemed to be unchanged after chronic treatment (2 X 10 mg/kg for 14 days). It is suggested that zimelidine produces a central antinociceptive effect, but elicits a peripheral hyperalgesia, which predominates in the formalin test.

Animals↗

Antinociceptive effects of (+/-)-, (+)- and (-)-nefopam in mice.

The antinociceptive activity of (+/-)-, (+)- and (-)-nefopam in mice has been examined using the hot-plate, formalin and tail-flick tests. Nefopam was administered by the intraperitoneal, intracerebroventricular (i.c.v.) and intrathecal (i.th.) routes. Intraperitoneal injection of (+/-)-nefopam (10-20 mg kg-1) had powerful analgesic effects in the hot-plate and formalin tests. In the tail-flick test it produced a weak, but significant elevation of the response latencies. In spinalized animals, however, the effect was abolished, indicating that nefopam prolonged the tail-flick latencies by activation of descending pain-modulating pathways. (+/-)-Nefopam (5-20 micrograms) elicited analgesia in the hot-plate test after i.c.v. or i.th. injection. These findings suggest that nefopam has both a spinal and a supraspinal site of action. (+)-Nefopam was significantly more potent than (-)-nefopam after both systemic and central administration.

Analysis of Variance↗

Intrathecal injection of capsaicin can be used as a behavioural nociceptive test in mice.

Intrathecal injections in mice of substance P (SP), capsaicin and kainic acid elicited a behavioural response similar to that caused by noxious stimulation. Although the agents have different mechanisms of action, they showed a similar response, consisting of biting, scratching and licking the caudal parts of the body. Activation of adenosine receptors in the spinal cord with 5-N-ethylcarboxamide adenosine (NECA) had no effect on the response to substance P or to kainic acid, but reduced the response to capsaicin. It is concluded that different substances, injected intrathecally, can be used to differentiate between pre- and postsynaptic induced nociceptive behaviour, and that this assay may be valuable in assessing central antinociceptive effects of various drugs, especially those affecting systems modulated by substance P.

Adenosine↗

Changes in nociception after 6-hydroxydopamine lesions of descending catecholaminergic pathways in mice.

Intrathecal (ITH) administration of 5 micrograms 6-hydroxydopamine (6-OHDA) in mice selectively lesioned descending catecholaminergic pathways. Uptake of 3H-noradrenaline (3H-NA) into synaptosomes from the lumbar spinal cord was reduced by 95%, without any change in the uptake of 14C-5-hydroxytryptamine (14C-5-HT). Synaptosomal uptake of 3H-NA and 14C-5-HT in the brain was not altered. The nociceptive sensitivity was evaluated using the tail-flick, hot plate and formalin tests 3 and 14 days after injection of 6-OHDA. At day 3 hyperalgesia was found in the hot-plate test, unchanged response latency in the tail-flick test and hypoalgesia in the formalin test. At day 14 there were no statistically significant differences from controls in any of the tests. The present findings support the contention that catecholaminergic pathways participate in the tonic regulation of nociception in the spinal cord. However, while supraspinally integrated responses to acute thermal pain, as measured with the hot-plate test, are inhibited by these pathways, responses to prolonged chemical pain are enhanced.

Animals↗

Effects of the putative 5-HT1A receptor agonist 8-OH-2-(di-n-propylamino)tetralin on nociceptive sensitivity in mice.

The ability of 8-OH-2-(di-n-propylamino)tetralin (8-OH-DPAT) to alter nociceptive sensitivity in mice was studied using the tail-flick, hot-plate and formalin tests. Subcutaneous (SC) administration of 8-OH-DPAT (0.63-1.0 mg/kg) dose-dependently increased the temperature at which hindpaw lick occurred in a hot-plate test using slowly rising temperature and increased the latencies to hindpaw lick, but reduced the latencies to jump in a conventional hot-plate test. Intracerebroventricular (ICV) injections (0.25-1.0 microgram) produced similar results in the conventional hot plate test. Following intrathecal (ITH) injections (0.25-1.0 microgram), however, the latencies to hindpaw lick were elevated without any change in jump latencies. In the formalin test a low systemic dose of 8-OH-DPAT (0.063 mg/kg) elicited hyperalgesia, while hypoalgesia was found after a high dose (1.0 mg/kg). ICV injection of 1.0 microgram produced hypoalgesia in the formalin test while the same dose injected ITH was without effect. 8-OH-DPAT did not alter tail-flick latencies, either by SC, ICV or ITH administration. Previous studies have shown that 8-OH-DPAT stimulates central serotonergic receptors, and shows selectivity for the 5-HT1A recognition site. The present findings indicate an involvement of 5-HT1A receptors in the processing of nociceptive information both at spinal and supraspinal sites. However, stimulation of 5-HT1A receptors does not seem to affect spinal, nociceptive reflexes.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Learned and pharmacologically-induced tolerance to ethanol and cross-tolerance to morphine and clonidine.

The development of tolerance to the inhibitory effect of ethanol on the tail-flick reflex was studied in the spinal rat. This preparation was used in order to avoid uncontrolled learning effects. Tolerance due to intoxicated practice (learned tolerance) and tolerance due to mere ethanol exposure (pharmacologically-induced tolerance) were studied in separate experiments. It was found that that learned tolerance to ethanol also caused tolerance to morphine and clonidine, whereas pharmacologically-induced tolerance did not have the same effect. The results challenge the concept of "behaviorally augmented tolerance" and suggest that learned and pharmacologically-induced tolerance involve different basal mechanisms in the CNS.

Animals↗

Acetylsalicylic acid, paracetamol and morphine inhibit behavioral responses to intrathecally administered substance P or capsaicin.

Intrathecally administered substance P (SP) or capsaicin in mice elicited a pain-related behavioral response consisting of vigorous biting, licking and scratching of the caudal part of the body. Pretreatment of the animals with intraperitoneally injected acetylsalicylic acid (300 and 400 mg/kg), paracetamol (300 and 400 mg/kg) and morphine (2.5 and 5 mg/kg) reduced the responses in a dose-dependent manner. The analgesia is probably mediated by inhibition of a postsynaptic SP sensitive mechanism. Thus these results demonstrate central antinociceptive effects of acetylsalicylic acid and paracetamol.

Acetaminophen↗

The putative serotonin receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin antagonizes the antinociceptive effect of morphine.

The effect of the selective 5-hydroxytryptamine (5-HT-1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on nociception and morphine analgesia was tested with the tail-flick method in mice. 8-OH-DPAT (0.06-1.0 mg/kg) had no apparent effect on the general behavior of the animals and did not change their reactivity to stimulation with noxious radiant heat. The compound did, however, dose-dependently attenuate the antinociception induced by administration of morphine hydrochloride (5.0 and 10.0 mg/kg). Thus, stimulation of a subpopulation of serotonin receptors may counteract the antinociceptive effect of morphine in the tail-flick test.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Changes in nociception after lesions of descending serotonergic pathways induced with 5,6-dihydroxytryptamine. Different effects in the formalin and tail-flick tests.

Intrathecal administration of 5,6-dihydroxytryptamine (5,6-DHT) in mice selectively lesioned descending serotonergic pathways. Nociception was evaluated 3 days after injection of 5,6-DHT using the tail-flick and formalin tests. In the tail-flick test shortened latencies were found in the lesioned animals. In contrast, the initial behavioural response (0-15 min) to formalin was reduced, while the late response (15-40 min) was not altered. Fourteen days after intrathecal administration of 5,6-DHT the changes in nociception, both in the tail-flick and in the formalin test, had returned to the control level. These findings support the contention that the raphe-spinal serotonergic system participates in the tonic regulation of nociception in the spinal cord. Apparently this system tonically inhibits spinal nociceptive reflexes, but tonically enhances the initial behavioural responses to noxious chemical stimulation, as measured with the formalin test.

5,6-Dihydroxytryptamine↗

Formalin test in mice, a useful technique for evaluating mild analgesics.

A modification of the formalin test appropriate for testing of mice is described. Formalin 1 or 5% was injected into the dorsal surface of a hindpaw, and the time the animal spent licking the paw was recorded. On the basis of the response pattern, two distinct periods of intensive licking activity were identified; an early (0-5 min after injection) and a late response (20-30 min after injection). The following analgesics were investigated (dose range): acetylsalicylic acid (100-400 mg/kg), paracetamol (100-400 mg/kg) and morphine (0.6-10 mg/kg). Acetylsalicylic acid (200-400 mg/kg early response, 300-400 mg/kg late response), paracetamol (200-400 mg/kg early response, 300-400 mg/kg late response) and morphine (2.5-10 mg/kg) inhibited the responses in a dose-dependent manner. The results indicate that the test is useful for evaluating mild analgesics. It may have advantages over some of the tests that are commonly used for testing analgesics.

Acetaminophen↗