Biomedical subjects

Françoise Godefroy

Publications and source records attributed to Françoise Godefroy.

5 recordsLinked to original sources

PubMed1992

A limited arthritic model for chronic pain studies in the rat.

Freund's adjuvant induced polyarthritis in rats has been used extensively to study pain processes of long duration. There are limitations of this model for chronic studies of pain/arthritis since the severe systemic changes provoke ethical concerns and also affect behaviour, physiology and biochemistry. Attempts to limit adjuvant-induced arthritis by plantar injection of the inoculum have been made. In this model, however, the process evolved to produce widespread polyarthritis if followed for the 6-plus-weeks necessary for chronic studies. Therefore, although it offers the researcher a reliable limited model of inflammation and nociception at the outset, for longer studies it may have all the disadvantages of the polyarthritic rat. The purpose of the present study was to produce a limited arthritic process in rats, stable over 6 weeks and suitable for behavioural and neurochemical studies of various chronic pain treatment methods. Injection (0.05 ml) of complete adjuvant containing 300 micrograms Mycobacterium butyricum in the tibio-tarsal joint produces a predictable monoarthritis, stable clinically and behaviourly from weeks 2 through 6 post injection. As revealed by clinical observations and X-ray examinations, the arthritis produced was limited anatomically, pronounced, prolonged and stable. A marked increase in sensitivity to paw pressure was seen in the affected limb. Animals gained weight and remained active, indicating little systemic disturbance as opposed to polyarthritic rats. We propose this limited model of arthritis as a suitable alternative to the polyarthritic rat for prolonged studies.

Animals↗

PubMed1987

Complex temporal changes in 5-hydroxytryptamine synthesis in the central nervous system induced by experimental polyarthritis in the rat.

The purpose of this study was to investigate modifications of 5-HT synthesis in a chronic pain model, the arthritic rat, at different times after the inoculation with Freund's adjuvant. This study confirms our previous findings that experimental induced polyarthritis is associated with a marked increase in free tryptophan levels in serum. During the acute phase of the disease (15-21 days after the adjuvant), the general increase in 5-HT synthesis observed in the CNS appeared to be related to an increase in tryptophan availability due to the elevation of free tryptophan in serum. During the post-acute phase of the disease (28-42 days after the adjuvant), the level of free tryptophan in the serum remained markedly increased but the levels in the CNS tended to return to normal values in all areas examined. At 42 days, 5-HT synthesis in the brain had also returned to normal values but was further increased at the spinal level. In addition, although 5-HT levels and 5-HT synthesis were increased in the dorsal as well as in the ventral part of the cord, an increase in the rate of disappearance of the amine after blockade of the decarboxylase (benserazide) was only observed in the dorsal part. This result tends to suggest that the descending serotonergic system projecting to the dorsal horn is preferentially activated during chronic pain.

Animals↗

PubMed1986

Do acute or chronic tricyclic antidepressants modify morphine antinociception in arthritic rats?

In a chronic pain model, the arthritic rat, tricyclic antidepressants (TCAs) have been shown to clearly reduce behavioural signs of nociception. In the present work, using a test of acute nociception (vocalization threshold to graded foot pressure) in the same model, we evaluated the possible potentiation of morphine analgesia by 2 TCAs: amitriptyline (AMIT) and imipramine (IMIP). Using this test of acute nociception, we failed to demonstrate any analgesic effect of AMIT or IMIP given either acutely or chronically. We also failed to demonstrate any potentiation of morphine by these compounds. On the contrary, we found a significant decrease of morphine antinociception after acute AMIT administration and a tendency towards diminution with both TCAs given chronically. These results appear to temper enthusiasm for human application of this combination. They also indicate that careful further studies in a chronic pain model using behaviour evaluations are necessary before definite conclusions can be drawn concerning TCAs/opiate interaction.

Amitriptyline↗

PubMed1985

Reduction of arthritis and pain behaviour following chronic administration of amitriptyline or imipramine in rats with adjuvant-induced arthritis.

Tricyclic antidepressants (TCAs) are used extensively to treat chronic pain in man without an adequate explanation for their activity. The purpose of the present study was to investigate this problem by testing the effect of chronic TCAs in an animal pain model: the arthritic rat. Sprague-Dawley rats with adjuvant-induced arthritis were injected daily for 4 weeks with amitriptyline (10 mg/kg) or imipramine (10 mg/kg) or saline, beginning 21 days after the induction of arthritis. Baseline evaluations were made prior to the injection series and at 4 weeks, 24 h after the last injection. Both TCAs significantly reduced 'scratching' and increased 'exploring' behaviour, without changing the response to graded foot pressure. In addition clinical signs of arthritis (ankle circumference, swelling, conjunctivitis, balanitis ...) were significantly reduced, while mobility was increased. This study shows that both amitriptyline and imipramine decrease pain behaviour and arthritis in this chronic pain model. Possible 'antiinflammatory' effects of TCAs and their eventual 'analgesic' effect will be discussed.

Amitriptyline↗

PubMed1980

Total and free serum tryptophan levels and brain 5-hydroxytryptamine metabolism in arthritic rats.

In rats suffering from experimentally induced arthritis produced by Freund's adjuvant, there is a marked decrease in total serum tryptophan levels and a marked increase in plasma-free tryptophan levels at both 15 and 21 days after the administration of the adjuvant. Tryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels are increased in the brain and the spinal cord at 15 days. However, 21 days after administration of the adjuvant these levels returned to normal values in the brain, but remained increased in the spinal cord. These results are in agreement with investigations suggesting the possible involvement of the raphe-spinal system in response to pain stimuli but are contrary to the observation that there is a large decrease in plasma-free tryptophan levels in arthritic human patients. These opposite results still question the hypothesis of a relationship between changes in plasma-free tryptophan levels and the severity of pain.

Animals↗