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Nitric oxide modulates the hyperalgesic response to mechanical noxious stimuli in sleep-deprived rats

Fabio Damasceno, Gabriela O Skinner, Paulo C Araújo, Marcia MD Ferraz, Frank Tenório and Olga MMS de Almeida*

Author affiliations

Department of Pharmacology and Psychobiology, Institute of Biology, State University of Rio de Janeiro, Av. 28 de Setembro, 87-Fundos, 20551-030, Rio de Janeiro, Brazil

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Citation and License

BMC Neuroscience 2013, 14:92  doi:10.1186/1471-2202-14-92

Published: 30 August 2013



Sleep restriction alters pain perception in animals and humans, and many studies have indicated that paradoxical sleep deprivation (PSD) promotes hyperalgesia. The hyperalgesia observed after mechanical nociceptive stimulus is reversed through nitric oxide synthase (NOS) inhibition. Both nitric oxide (NO) and the dorsolateral periaqueductal gray matter (dlPAG) area of the brainstem are involved in hyperalgesia. Thus, in this work, we investigated the pain-related behavior response after mechanical noxious stimuli (electronic von Frey test), and the activity of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), an indicator of NOS activity, within the dlPAG of paradoxical sleep-deprived rats. We also evaluated the effects of pre-treatment with L-NAME on these parameters.


These data revealed that PSD reduced the hindpaw withdrawal threshold (−47%, p < 0.0001) confirming the hyperalgesic effect of this condition. In addition, there were more NADPH-d positive cells in dlPAG after PSD than in control rats (+ 59%, p < 0.0001). L-NAME treatment prevented the reduction in the hindpaw withdrawal threshold (+ 93%, p < 0.0001) and the increase in the NADPH-d positive cells number in the dlPAG of PSD-treated rats (−36%, p < 0.0001).


These data suggest that the hyperalgesic response to mechanical noxious stimuli in paradoxical sleep-deprived rats is associated with increased NOS activity in the dlPAG, which presumably influences the descending antinociceptive pathway.

Paradoxical sleep deprivation; Nociception; NADPH-d; L-NAME