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The Journal of Neuroscience, December 3, 2003, 23(35):11120-11126

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Behavioral/Systems/Cognitive
Analgesia Induced by Dietary Restriction Is Mediated by the -Opioid System

Mercedes de los Santos-Arteaga, Sergio A. Sierra-Domínguez, German H. Fontanella, José M. Delgado-García, and Ángel M. Carrión

División de Neurociencias, Universidad Pablo de Olavide de Sevilla, 41013 Sevilla, Spain

Progress in the control and treatment of pain may be facilitated by a better understanding of mechanisms underlying nociceptive processing. Here we show that mice subjected to an intermittent fasting diet (IFD) display markedly reduced responses in models of thermal and visceral pain compared with mice fed ad libitum (AL). Pharmacological analyses suggest that a change in the endogenous -opioid system underlies IFD-induced analgesia. The levels of prodynorphin mRNA and -opioid receptors in the spinal cord are higher in IFD than in AL mice. Furthermore, in spinal cord nuclear protein extracts, the activity of the transcriptional repressor DREAM (downstream regulatory element antagonist modulator), the main regulator of prodynorphin expression, is lower in IFD than in AL mice. Finally, c-Fos expression in dorsal spinal cord after noxious stimulation is significantly lower in IFD than in AL animals, indicating that dynorphin could block nociceptive information at the spinal cord. These results suggest that dietary restriction together with administration of -opioid agonists could be useful as a new therapeutic approach for pain relief.

Key words: c-Fos; DREAM; dynorphin; intermittent fast diet; pain relief; spinal cord

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Received July 15, 2003; revised October 3, 2003; accepted October 9, 2003.

This article has been cited by other articles:

				A. Fontan-Lozano, J. L. Saez-Cassanelli, M. C. Inda, M. de los Santos-Arteaga, S. A. Sierra-Dominguez, G. Lopez-Lluch, J. M. Delgado-Garcia, and A. M. Carrion Caloric Restriction Increases Learning Consolidation and Facilitates Synaptic Plasticity through Mechanisms Dependent on NR2B Subunits of the NMDA Receptor J. Neurosci., September 19, 2007; 27(38): 10185 - 10195. [Abstract] [Full Text] [PDF]

				M. C. Inda, J. M. Delgado-Garcia, and A. M. Carrion Acquisition, Consolidation, Reconsolidation, and Extinction of Eyelid Conditioning Responses Require De Novo Protein Synthesis J. Neurosci., February 23, 2005; 25(8): 2070 - 2080. [Abstract] [Full Text] [PDF]

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