Recent evidence points to the gut microbiota as a regulator of brain and behavior, although it remains to be determined if gut bacteria play a role in
chronic pain. The
endocannabinoid system is implicated in
inflammation and
chronic pain processing at both the gut and central nervous system (CNS) levels. In the present study, we used low
Vitamin D dietary intake in mice and evaluated possible changes in gut microbiota,
pain processing and
endocannabinoid system signaling.
Vitamin D deficiency induced a lower microbial diversity characterized by an increase in Firmicutes and a decrease in Verrucomicrobia and Bacteroidetes. Concurrently,
vitamin D deficient mice showed
tactile allodynia associated with neuronal hyperexcitability and alterations of
endocannabinoid system members (endogenous mediators and their receptors) at the spinal cord level. Changes in
endocannabinoid (
anandamide and 2-arachidonoylglycerol) levels were also observed in the duodenum and colon. Remarkably, the anti-inflammatory
anandamide congener,
palmitoylethanolamide, counteracted both the
pain behaviour and spinal biochemical changes in
vitamin D deficient mice, whilst increasing the levels of Akkermansia, Eubacterium and Enterobacteriaceae, as compared with vehicle-treated mice. Finally, induction of spared nerve injury in normal or
vitamin D deficient mice was not accompanied by changes in gut microbiota composition. Our data suggest the existence of a link between
Vitamin D deficiency - with related changes in gut bacterial composition - and altered nociception, possibly via molecular mechanisms involving the
endocannabinoid and related mediator signaling systems.