Effects of Peripheral Axotomy on Cholecystokinin Neurotransmission in the
Rat Spinal Cord |
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Authors: | João Manuel Antunes Bras Anne-Marie Laporte Jean Jacques Benoliel Sylvie Bourgoin Annie Mauborgne Michel Hamon François Cesselin & Michel Pohl |
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Institution: | INSERM U 288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, Facultéde Médecine Pitié-Salpêtrière, Paris, France |
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Abstract: | Abstract : Because cholecystokinin (CCK) acts as a "functional" endogenous opioid antagonist, it has been proposed that changes in central CCKergic neurotransmission might account for the relative resistance of neuropathic pain to the analgesic action of morphine. This hypothesis was addressed by measuring CCK-related parameters 2 weeks after unilateral sciatic nerve section in rats. As expected, significant decreases (-25-38%) in the tissue concentrations and in vitro release of both substance P and calcitonin gene-related peptide were noted in the dorsal quadrant of the lumbar spinal cord on the lesioned side. In contrast, the tissue levels and in vitro release of CCK were unchanged in the same area in lesioned rats. Measurements in dorsal root ganglia at L4-L6 levels revealed no significant changes in proCCK mRNA after the lesion. However, sciatic nerve section was associated with a marked ipsilateral increase in both CCK-B receptor mRNA levels in these ganglia (+70%) and the autoradiographic labeling of CCK-B receptors by 3H]pBC 264 (+160%) in the superficial layers of the lumbar dorsal horn. Up-regulation of CCK-B receptors rather than CCK synthesis and release probably contributes to increased spinal CCKergic neurotransmission in neuropathic pain. |
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Keywords: | Cholecystokinin CCK-B receptor Gene expression Sciatic nerve section Spinal cord Dorsal root ganglia |
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