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Jean-Marie Besson

Publications and source records attributed to Jean-Marie Besson.

23 records · Page 2Linked to original sources

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↗

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↗

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↗

Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat.

(1) Sixty-eight convergent dorsal horn neurones have been recorded at the lumbar level in anaesthetized intact rats. All cells received prominent A alpha and C fibre afferents and correspondingly could be activated by high and low threshold stimuli applied to the peripheral excitatory receptive field. (2) The activity of 67/68 of these neurones was powerfully inhibited by noxious stimuli applied to various parts of the body. Since non-noxious stimuli were ineffective in this respect, the term "diffuse noxious inhibitory controls" (DNIC) is proposed. (3) DNIC could be evoked by noxious pinch applied to the tail, the contralateral hind paw, the forepaws, the ears and the muzzle; the most effective areas were the tail and muzzle. Noxious heat applied to and transcutaneous electrical stimulation of the tail were extemely effective in eliciting DNIC as was the intraperitoneal injection of bradykinin. (4) DNIC strongly depressed by 60-100% both the C fibre response following suprathreshold transcutaneous electrical stimulation and the responses to noxious radiant heat. (5) The spontaneous activity and the responses to low threshold afferents induced either by A alpha threshold electrical or natural stimulation were also powerfully inhibited. (6) In the majority of cases, long lasting post-effects directly related to the duration of conditioning painful stimulus were observed.

Animals↗

Diffuse noxious inhibitory controls (DNIC). II. Lack of effect on non-convergent neurones, supraspinal involvement and theoretical implications.

(1) Diffuse noxious inhibitory controls (DNIC) were tested for their effect on noxious only, non-noxious and proprioceptive cells in the dorsal horn of the intact anaesthetized rat. Unlike convergent neurones, as described in the previous paper, there was no effect of DNIC on these neurones. It is concluded that convergent neurones are specifically inhibited by DNIC. (2) The effect of DNIC could not be demonstrated for convergent neurones in the spinal animal. Thus the neuronal substrate for DNIC must involve supraspinal structures. (3) Because of the level of firing in convergent neurones induced by hair and touch receptors, presumably constantly and randomly activated in the freely moving animal, a noxious message arriving at higher centres may be partly masked by this background noise. On the basis of the known role of convergent neurones in nociception, we propose the following mechanism which may interpret this paradoxical convergence: two pools of convergent neurones are influenced by a painful peripheral stimulation, one segmental pool being activated whilst the remaining population of cells is inhibited; the "contrast" between the messages from these two pools may well produce a significant pain signalling output from the convergent dorsal horn cells. (4) These results and their theoretical implications are discussed with regard to the concept of the "analgesic system", certain clinical observations and the paradoxical pain relieving effects of counterirritation and some forms of acupuncture.

Acupuncture Therapy↗