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Odd-Geir Berge

Publications and source records attributed to Odd-Geir Berge.

10 recordsLinked to original sources
PubMed2003

COX-inhibiting nitric oxide donators (CINODs) - a new paradigm in the treatment of pain and inflammation.

The clinical utility of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief is tempered by their propensity to cause gastrointestinal toxicity. Cyclooxygenase (COX)-inhibiting nitric oxide donators (CINODs) are a new class of drugs designed to provide analgesic efficacy through COX inhibition and gastrointestinal safety through the protective effects of controlled nitric oxide donation. Pre-clinical studies assessing the pharmacology, efficacy and gastrointestinal safety of AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] support this concept. Based on these studies, AZD3582 was the first CINOD to enter clinical development for the treatment of acute and chronic pain. The potential clinical utility of this new class is illustrated by a study of AZD3582 in healthy volunteers in which it caused significantly less acute gastrointestinal toxicity than an equimolar dose of naproxen. The results of the animal studies and the initial clinical study warrant long-term tolerability studies of AZD3582 along with evaluation of its anti-inflammatory and analgesic effects in humans.

Journal Article↗
PubMed2002

Pathogenesis of sciatic pain: a study of spontaneous behavior in rats exposed to experimental disc herniation.

STUDY DESIGN: A new way to study pain in experimental animals without handling of the animals and based on registration of spontaneous behavior using video recordings. OBJECTIVES: To evaluate if experimental disc herniation in the rat may induce changes in spontaneous behavior. SUMMARY OF BACKGROUND DATA: The knowledge regarding the basic pathophysiologic mechanisms of sciatica has increased dramatically during the last decade. However, studies have mainly assessed nerve dysfunction rather than pain. Existing methods to study pain generally comprise a certain amount of handling and registration of changes in sensory thresholds. In the present study we introduce a new way to assess pain that focuses on changes in behavior rather than on changes in thresholds. METHODS: Forty rats were divided equally into four experimental series: sham exposure of the left L4 dorsal root ganglion, exposure of the left L4 dorsal root ganglion and incision of the L4-L5 disc, exposure and slight displacement of the left L4 dorsal root ganglion, and combination of disc incision and displacement. The rats were videotaped the day before surgery and on day 1, 3, 7, 14, and 21 after surgery. Spontaneous behavior was categorized into 10 behaviors and recorded during 20 minutes of observation. RESULTS: Disc incision and displacement per se did not induce any behaviors different from that observed in the sham-operated group. In the series with the combination of disc incision and displacement there was increased focal pain, seen as increased lifting of the hind paw on the operated side and increased rotation of the head toward the operated side. This pain pattern was most pronounced the day after surgery. Fourteen days after surgery there were no detectable differences in behavior between this group and the sham group. At day 21 after surgery, however, another picture of increased immobility and decreased locomotion was seen in this group, possibly indicating more generalized pain. CONCLUSIONS: The study demonstrates that it is possible to detect changes in spontaneous behavior after experimental disc herniation. However, such changes may only be seen if disc incision and slight mechanical deformation are combined. This is in agreement with previous clinical and experimental observations. The present model allows for convenient assessment of pain in a way that focuses on spontaneous behavior rather than changes in pain thresholds and that reduces the interference of the researcher and environment on the outcome of the assessment.

Animals↗
PubMed1994

The NMDA antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) has antinociceptive effect after intrathecal injection in the rat.

This behavioral study was performed in order to delineate the antinociceptive effects of and the influence on motor function of a highly potent, competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). After intrathecal (i.t.) administration of CPP to chronically catheterized rats, antinociception was studied in 3 different nociceptive tests: the tail-flick test, the hot-plate test, and the formalin test. The lowest dose producing visible motor dysfunction was 1 nmol, with 2 of 8 animals showing slight ataxia. Dose-related motor dysfunction and apparent sedation was present after 5 and 10 nmol. Dose-related antinociception was evident in the thermal tests following doses that produced little or no motor dysfunction. In the tail-flick test, the antinociceptive effect was attenuated at higher doses, resulting in a bell-shaped dose-response relationship. Dose-related antinociception was found in both the first and second phase of the formalin test following doses from 0.25 up to 1 nmol. The present study shows that the competitive NMDA antagonist CPP has an antinociceptive effect in doses that do not affect motor function. Furthermore, antinociception was evident in both phasic and tonic nociceptive tests. Finally, the dose-response relationship in the tail-flick test was bell-shaped. As discussed this indicates that NMDA receptors may be involved in functionally divergent nociceptive systems.

Analgesics↗
PubMed1992

The formalin test: an evaluation of the method.

The formalin test for nociception, which is predominantly used with rats and mice, involves moderate, continuous pain generated by injured tissue. In this way it differs from most traditional tests of nociception which rely upon brief stimuli of threshold intensity. In this article we describe the main features of the formalin test, including the characteristics of the stimulus and how changes in nociceptive behaviour may be measured and interpreted. The response to formalin shows an early and a late phase. The early phase seems to be caused predominantly by C-fibre activation due to the peripheral stimulus, while the late phase appears to be dependent on the combination of an inflammatory reaction in the peripheral tissue and functional changes in the dorsal horn of the spinal cord. These functional changes seem to be initiated by the C-fibre barrage during the early phase. In mice, the behavioural response in the late phase depends on the ambient temperature. We argue that the peripheral tissue temperature as well as other factors influencing the peripheral inflammation may affect the response, possibly confounding the results obtained with the test. Furthermore, we discuss the methods of recording the response and the value of observing more than one aspect of behaviour. Scoring of several behavioural variables provides a means of assessing motor or sensorimotor function as possible causes for changes in behaviour. In conclusion, the formalin test is a valuable addition to the battery of methods available to study nociception.

Animals↗
PubMed1992

Intrathecal co-administration of substance P and NMDA augments nociceptive responses in the formalin test.

The effects of intrathecal administration of substance P and N-methyl-D-aspartate (NMDA) were studied in the formalin test in mice. Both substances were administered 5 min before injection of formalin into the hind paw. Co-administration of substance P and NMDA intensified the response in both the 1st (0-10 min) and the 2nd phase (20-30 min) of the formalin test, and increased the duration of the response. The increase in the response to formalin depended on the formalin concentration and was significant with 1% and 5% concentrations of formalin but not with a 0.05% concentration. No increase in the response was observed when NMDA or substance P was given alone. These findings indicate that concurrent activation of spinal NMDA and substance P receptors induces an enhancement of spinal transmission of nociception, and that this enhancement is dependent on the intensity or the quality of the peripheral stimulus.

Animals↗
PubMed1988

Apparent hyperalgesia after lesions of the descending serotonergic pathways is due to increased tail skin temperature.

It has been suggested that the descending serotonergic pathways exercise a tonic inhibition on nociception in the spinal cord. In this study 5,6-dihydroxytryptamine (5,6-DHT, 20 micrograms base) injected intrathecally in rats reduced spinal serotonin concentration to 3.5% of control levels without significantly affecting spinal noradrenaline. The lesion reduced the mean tail-flick latency by approximately 35% and increased the mean tail skin temperature by approximately 3.5 degrees C; both parameters gradually returned to normal values within 2-3 weeks. Both in controls and in lesioned animals there was a highly significant negative correlation between tail skin temperature and tail-flick latency. Multiple regression analysis showed that the effect of lesioning on tail-flick latency was non-significant when the effect of skin temperature was taken into account. Thus the reduced tail-flick latency after lesions of descending serotonergic pathways, usually interpreted as increased nociception, may be due to changes in tail skin temperature.

5,6-Dihydroxytryptamine↗
PubMed1986

Dissociation between antinociceptive and anti-inflammatory effects of acetylsalicylic acid and indomethacin in the formalin test.

It is assumed that the mild analgesia produced by acetylsalicylic acid (ASA) and indomethacin is due to a common mode of action, namely inhibition of the cyclo-oxygenase reaction in the synthesis of prostaglandins. It has, however, been difficult to separate the influence of the anti-inflammatory activity from pure analgesia in standard animal tests using a fully developed inflammatory state. In the present experiments a modification of the formalin test in mice is used. Licking of the injected paw is recorded after the injection of a small nociceptive amount of formalin (20 microliters, 1%). The results show that the response to formalin is biphasic with an early (0-5 min) and a late (20-30 min) phase of high licking activity. ASA had a dose-dependent antinociceptive effect during both the early and the late phases. In contrast, antinociceptive effect of indomethacin was found only during the late phase. On the basis of these results it may be suggested that inhibition of the cyclo-oxygenase reaction has no major effect on the early phase in the formalin test. This also suggests that ASA and indomethacin are antinociceptive through partially different modes of action. In addition to an anti-inflammatory effect common to both drugs, ASA may have a direct antinociceptive action.

Animals↗
PubMed1982

Effects of 5-HT receptor agonists and antagonists on a reflex response to radiant heat in normal and spinally transected rats.

Tail-flick latency (TFL) was tested in intact and spinally transected rats. Spinal transection permanently lowered the TFL by 25-30%. A diurnal rhythm in nociception was found in intact but not in spinal rats with maximum sensitivity during the early light period. Administration of the 5-hydroxytryptamine (5-HT) receptor antagonists metergoline (0.06-2.0 mg/kg), mianserin (1.0 and 5.0 mg/kg) or methiothepin (0.1-2.5 mg/kg) reduced the TFL of normal rats to the same level as that of the transected animals. The diurnal variation in TFL was also abolished by metergoline. Neither drug changed the TFL of the transected rats. The 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 0.5-2.0 mg/kg) induced the 5-HT syndrome in intact rats and elicited spinal reflexes in the transected animals. Concomitantly, the TFLs of both groups were elevated to the same maximum level, approximately 25% above normal TFL of intact rats. Transected rats consistently responded to lower doses than intact rats, indicating 5-HT receptor supersensitivity. The 5-MeODMT effects were reversed by administration of 5-HT antagonists. Administration of the 5-HT precursor dl-5-hydroxytryptophan (200 mg/kg), after inhibition of peripheral decarboxylation by carbidopa (75 mg/kg), also elevated the TFL and induced other behavioral signs of 5-HT stimulation. It is concluded tht there exists a tonic inhibitory influence with diurnal variations on spinal nociceptive reflexes in the rat. The data reported suggest that this inhibition is mediated by descending 5-HT pathways.

5-Hydroxytryptophan↗