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In Vivo SiRNA Transfection and Gene Knockdown in Spinal Cord via Rapid Noninvasive Lumbar Intrathecal Injections in Mice
Published on: March 22, 2014
Indirect effects of intrathecal morphine upon diffuse noxious inhibitory controls (DNICs) in the rat
Luis Villanueva1, Daniel Le Bars
1Unité de Recherches de Neurophysiologie Pharmacologique, INSERM (U. 161), 2 rue d'Alésia, 75014 Paris France.
Abstract:
Diffuse noxious inhibitory controls (DNICs) affect all convergent neurones recorded in the dorsal horn of the spinal cord or the nucleus caudalis of the trigeminal system. They are triggered specifically by heterotopic noxious stimulation. DNICs acting at the trigeminal level were triggered by noxious thermal stimulation of caudal parts of the body, and the effects of intrathecal morphine applied at the coccygeal level were tested. The immersion of the right hind paw or of the tail induced inhibitions on C-fibre responses of trigeminal convergent neurones of 95.8 +/- 2.8% and 93.8 +/- 2.4+ respectively. Intrathecal morphine (15 micrograms; 20 microliters) produced an almost complete blockade of inhibitions triggered from the tail without significantly affecting those triggered from the hind paw. A reversal by systemic naloxone (0.4 mg/kg i.v.) was obtained in all cases. These results indicate that intrathecal morphine induced a segmental depression of nociceptive messages strong enough to prevent the spinal initiation of DNICs. We suggest that the segmental depression of nociceptive transmission induced by morphine led to a consequent blockade of DNICs acting on the whole population of convergent neurones not initially affected by the noxious stimulus. These findings are discussed with regard to the strong analgesic effects of intrathecal morphine observed in both behavioural and clinical studies.

