Abstract
BackgroundNeuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. To date, the current pharmacological treatments for neuropathic pain are still unsatisfactory. The gut microbiota reportedly plays important roles in inducing neuropathic pain, so probiotics have also been used to treat it. However, the underlying questions around the interactions in and stability of the gut microbiota in a spared nerve injury-induced neuropathic pain model and the key microbes (i.e., the microbes that play critical roles) involved have not been answered. We collected 66 fecal samples over 2 weeks (three mice and 11 time points in spared nerve injury-induced neuropathic pain and Sham groups). The 16S rRNA gene was polymerase chain reaction amplified, sequenced on a MiSeq platform, and analyzed using a MOTHUR- UPARSE pipeline.ResultsHere we show that spared nerve injury-induced neuropathic pain alters gut microbial diversity in mice. We successfully constructed reliable microbial interaction networks using the Metagenomic Microbial Interaction Simulator (MetaMIS) and analyzed these networks based on 177,147 simulations. Interestingly, at a higher resolution, our results showed that spared nerve injury-induced neuropathic pain altered both the stability of the microbial community and the key microbes in a gut micro-ecosystem. Oscillospira, which was classified as a low-abundance and core microbe, was identified as the key microbe in the Sham group, whereas Staphylococcus, classified as a rare and non-core microbe, was identified as the key microbe in the spared nerve injury-induced neuropathic pain group.ConclusionsIn summary, our results provide novel experimental evidence that spared nerve injury-induced neuropathic pain reshapes gut microbial diversity, and alters the stability and key microbes in the gut.
Highlights
Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli
Pain withdrawal threshold decreased after spared nerve injury (SNI)-induced neuropathic pain We used the SNI model to investigate the influence of traumatic peripheral nerve injury on the interactions and stability of the gut microbiota and its key microbes
After the traumatic peripheral nerve injury, the paw withdrawal thresholds were significantly lower in the SNI group than in the Sham group on days 1 (p value: 0.033), 2 (p value: 0.003), 4 (p value: 0.020), 5 (p value: 0.003), 6 (p value: 0.049), and 7 (p value: 0.012) (Fig. 1b)
Summary
Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. The underlying questions around the interactions in and stability of the gut microbiota in a spared nerve injury-induced neuropathic pain model and the key microbes (i.e., the microbes that play critical roles) involved have not been answered. Neuropathic pain can cause increased pain sensitivity to mechanical or thermal stimuli [20]. Current pharmacological treatments for neuropathic pain are still unsatisfactory because the causes of chronic pain cannot always be established [9]. A recent study attempted to use probiotics (i.e., Lactobacillus reuteri lr or Bifidobacterium bl5b) to alleviate SNI (spared-nerve injury; a traumatic peripheral nerve injury)-induced neuropathic pain, but failed [42]
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