Biomedical subjects

Kjell Hole

Publications and source records attributed to Kjell Hole.

22 records · Page 2Linked to original sources

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↗

PubMed1988

Modification of the antinociceptive effect of morphine by acute and chronic administration of clomipramine in mice.

The antinociception effect of clomipramine and the combination of clomipramine and morphine was evaluated using the constant temperature hot plate test, the increasing temperature hot plate test and the formalin test in mice. Both a single dose of clomipramine (10 mg/kg) given intraperitoneally (i.p.) and chronic clomipramine treatment (10 mg/kg/day, i.p., for 7 days) induced antinociception. When morphine (5 mg/kg), given subcutaneously (s.c.), and clomipramine were combined, an increased antinociceptive effect compared to morphine alone was observed in all tests. In the increased temperature hot plate test and in the formalin test increased antinociception was also observed when morphine was combined with chronic clomipramine treatment. In the constant temperature hot plate test no additional effect compared to morphine alone was observed when morphine and chronic clomipramine treatment were combined. These results indicate that clomipramine has an antinociceptive effect in itself, and that it may enhance the antinociceptive effects of morphine. The differences between the tests indicate that different nociceptive mechanisms are involved, and that the combination of clomipramine and morphine may be beneficial for some types of nociceptive stimuli, but not for others.

Animals↗

PubMed1987

The formalin test in mice: dissociation between inflammatory and non-inflammatory pain.

The formalin test in mice is a valid and reliable model of nociception and is sensitive for various classes of analgesic drugs. The noxious stimulus is an injection of dilute formalin (1% in saline) under the skin of the dorsal surface of the right hindpaw. The response is the amount of time the animals spend licking the injected paw. Two distinct periods of high licking activity can be identified, an early phase lasting the first 5 min and a late phase lasting from 20 to 30 min after the injection of formalin. In order to elucidate the involvement of inflammatory processes in the two phases, we tested different classes of drugs in the two phases independently. Morphine, codeine, nefopam, and orphenadrine, as examples of centrally acting analgesics, were antinociceptive in both phases. In contrast, the non-steroid anti-inflammatory drugs indomethacin and naproxen and the steroids dexamethasone and hydrocortisone inhibited only the late phase, while acetylsalicylic acid (ASA) and paracetamol were antinociceptive in both phases. The results demonstrate that the two phases in the formalin test may have different nociceptive mechanisms. It is suggested that the early phase is due to a direct effect on nociceptors and that prostaglandins do not play an important role during this phase. The late phase seems to be an inflammatory response with inflammatory pain that can be inhibited by anti-inflammatory drugs. ASA and paracetamol seem to have actions independent of their inhibition of prostaglandin synthesis and they also have effects on non-inflammatory pain.

Acetaminophen↗

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↗