Douleurs neuropathiques - page 11 - Publications Scientifiques

Dernière publication 14/12/2008

Antinociceptive and anti-allodynic effects of oral PL37- a complete inhibitor of

Vincristine is a common anti-cancer therapy administered for the treatment of many types of tumors. Its dose-limiting side effect is the production...

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    [title] => Antinociceptive and anti-allodynic effects of oral PL37- a complete inhibitor of
    [paragraph] => Antinociceptive and anti-allodynic effects of oral PL37, a complete inhibitor of enkephalin-catabolizing enzymes, in a rat model of peripheral neuropathic pain induced by vincristine.
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Authors
T. Karine, E. Bonnard, S. Dubacq, M. C. Fournié-Zaluski, B. Roques et al.

 Lab
ESPCI-CNRS UMR 7637, Paris, France.
Journal
European Journal of Pharmacology
Abstract
Vincristine is a common anti-cancer therapy administered for the treatment of many types of tumors. Its dose-limiting side effect is the production of peripheral neuropathy, resulting in chronic neuropathic pain in many patients. An animal model of vincristine-induced sensory neuropathy was developed after repeated intraperitoneal injection in male rats and used in the present work to study the effects of PL37, an orally active complete dual inhibitor of enkephalin-catabolizing enzymes, on mechanical hypersensitivity and allodynia and on cold allodynia. We used the Electronic Von Frey filament (mechanical static allodynia), acetone test (cold allodynia), and a new behavioural test we first describe in this study, the “paint-brush test” which evaluates dynamic mechanical allodynia and dynamic mechanical hypersensitivity. We used a smooth paint brush leading to an innocuous stimulus, and a rough-one leading to an intense mechanical stimulus. Mechanical hypersensitivity and allodynia due to vincristine-induced neuropathy, but not cold allodynia, are strongly reduced by oral or i.p. injected PL37, the dose-dependent effects being reversed by naloxone-methiodide supporting the peripheral action of the dual inhibitor. These results show that enkephalins protected from degradation by PL37 could bind to peripheral opioid receptors expressed only on C- and A_-mechanonociceptors but not on cold thermonociceptors. The fact that PL37 is also active on small intensity mechanical stimulus could reveal an expression of opioid receptors on low threshold mechanoreceptors in the vincrisitine-evoked pathological conditions. Thus the increase in endogenous enkephalin levels induced by PL37 offers a new way to reduced neuropathic pain without the possible side effects of opiates.
BIOSEB Instruments Used
Electronic Von Frey 4 (BIO-EVF4),Electronic Von Frey 5 with embedded camera (BIO-EVF5)
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Une solution rapide pour déterminer le seuil de sensibilité à la douleur mécanique chez les rongeurs (rats et souris). Maintenant en version sans-fil, pour être libéré des câbles!

Cet instrument électronique précis et simple d'utilisation est le test de référence pour vos recherches en analgésie, nociception, neuropathies et douleurs post-opératoires

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En tant que version électronique du classique esthésiomètre à filaments de Von Frey, la dernière évolution de l’instrument électronique Von Frey de Bioseb, conçu pour déterminer le seuil de sensibilité mécanique chez les rongeurs (rats et souris) par stimulation sous la patte, est un outil indispensable pour vos recherches sur l’hyperalgésie et l’allodynie. En mesurant et en enregistrant la force à laquelle l’animal présente un réflexe de retrait de la patte, il est possible d’étudier les pathologies liées à la réponse sensorielle ainsi qu’à l’hyper- ou l’hypoesthésie.
L'EVF5 intègre une caméra embarquée au niveau de la zone de stimulation et fonctionne avec un nouveau logiciel dédié révolutionnaire

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