Anti-nociceptive effects of caloric restriction on neuropathic pain in rats involves silent information regulator 1

Caloric restriction (CR) increases both average and maximum lifespan, retards physiological signs of ageing, and delays the onset of several diseases and may mediate neuropathic pain. Neuropathic pain seriously affects the quality of life of patients. In this study, we investigated whether CR exerts anti-nociceptive effects on neuropathic pain, and probed its potential mechanisms.

Adult rats were divided into two dietary groups: an ad libitum (AL)-fed group and a CR group, which was provided with 60% of the food intake of AL rats for 6 weeks. The effects of 6-week CR on pain behaviour and neuro-inflammation induced by chronic constriction injury of the sciatic nerve were evaluated.

Rats subjected to a CR diet had reduced hypersensitivity to mechanical and thermal stimuli after nerve-constriction injury. CR increased the silent information regulator 1 (SIRT1) expression, and suppressed the nerve-constriction-induced production of mitochondrial-derived reactive oxygen species and activation of nuclear factor kappa B accompanied by suppression of mature interleukin-1β production in the ipsilateral spinal cord dorsal horn. The inhibition of SIRT1 reversed the effects of caloric restriction on pain behaviours. Moreover, CR decreased the phosphorylation of N-methyl-d-aspartate receptor subunits and the mitogen-activated protein kinase family, decreased the sensory neurone excitability, and inhibited the nerve-constriction-induced glial-cell activation.

These results suggest that the effects of CR on pain behaviours in a rat model of nerve injury are via inhibition of excessive neuro-inflammation induced by the injury. CR may be of benefit in patients with neuropathic pain.