A role for gut microbiota in early-life stress-induced widespread muscle pain in the adult rat

Abstract

Adult rats that experienced neonatal limited bedding (NLB), a form of early-life stress, experience persistent muscle mechanical hyperalgesia. Since there is a growing recognition that the gut microbiome regulates pain and nociception, and that early-life stress produces a long-lasting impact on the gut microbiome, we tested the hypothesis that persistent muscle hyperalgesia seen in adult NLB rats could be ameliorated by interventions that modify the gut microbiome. Adult NLB rats received probiotics, either Lactobacillus rhamnosus GG (10 billion CFU/150 ml) or De Simone Formulation (DSF) (112.5 billion CFU/150 ml mixture of 8 bacterial species), in their drinking water, or non-absorbable antibiotics, rifaximin or neomycin, admixed with cookie dough, to provide 50 mg/kg. Mechanical nociceptive threshold in the gastrocnemius muscle was evaluated before and at several time points after administration of probiotics or antibiotics. Adult NLB rats fed probiotics L. Rhamnosus or DSF, antibiotics, as well as rats fed non-absorbable antibiotics rifaximin or neomycin, had markedly attenuated muscle mechanical hyperalgesia. We hypothesize that persistent skeletal muscle hyperalgesia produced by NLB stress may be, at least in part, due to a contribution of the gut microbiome, and that modulation of gut microbiome using probiotics or non-absorbable antibiotics, may be novel therapeutic approaches for the treatment of chronic musculoskeletal pain.

MafK accelerates Salmonella mucosal infection through caspase-3 activation

“…The pathophysiology of IBD is aggravated by the dysregulation of the intestinal immune response. To investigate whether the local immune response could be activate by MafK in the gastrointestinal tract, a dose of 5×10 7 CFU Salmonella was given orally to the mice. The results showed that MafK has a negative effect on gut homeostasis.…”

“…The assay was used to examine the in vivo intestinal permeability. First, 5×10 7 CFU of Salmonella or PBS was orally administrated to MafK and WT mice after pretreated with Streptomycin. After 48 h, fast mice for 4 h prior to the assay, but free to water.…”

“…The cross talk between IECs and intestinal microbiota are also essential for intestinal homeostasis [ 4 ]. The response of IECs to signals provided by commensal microbiome that plays a role in disease progression regulation, such as type 2 diabetes mellitus, stress and depression [ 5 – 7 ]. Breakdown of the homeostasis of IECs leads to intestinal disorder, to give an example inflammatory bowel disease (IBD).…”

Microbiota and Pain: Save Your Gut Feeling

“…In 2015, the non-absorbable antibiotic rifaximin received FDA approval for the treatment of diarrhea-predominant IBS [27]. Rifaximin, neomycin or specific probiotics (i.e., L. rhamnosus GG or De Simone formulation which is a highconcentration probiotic preparation of eight live freeze-dried bacterial species [75]) may reduce stress-induced hyperalgesia, skeletal muscle hyperalgesia, neuropathic cutaneous mechanical allodynia and thermal hyperalgesia by altering the microbiota [76].…”

“…The translocation of LPS, cytokines and bacteria causes the reduction of nociceptive threshold and the increase of neuronal excitability that contribute to hyperalgesia. Early life stress can also modify the nociceptor sensitivity by modulation of vagal afferent activity [76]. Interestingly, an increased risk of infantile colic has been reported in infants born preterm or who were submitted to antibiotic treatment in the first days of life [91].…”