The therapeutic index (TI) inversely varied as a function of amount of SNC80 in the mixture, such that lower amounts of SNC80 produced a higher TI, and larger amounts produced a lower TI. Compared to literature using standard pain-elicited assays, the orderly relationship between SNC80 and TI reported here may be a unique function of assessing pain-depressed behavior.

No abstract

Given the reported effects of gut microbiome modulation on local gut inflammation and intestinal pain, it is possible that gut microbiota regulate persistent or chronic pain conditions that are distal to the gut, including pain states in the extremities. This study evaluated the effects of gut microbiome modulation on formalin pain‐depressed behaviors and formalin‐induced paw inflammation in female Fisher rats. Pilot data indicate that (1) a two‐week regimen of the narrow‐spectrum gram‐positive antibiotic vancomycin (500mg/L) in drinking water depleted Firmicutes and Bacteroidetes diversity / density in rats with or without access to running wheels; (2) formalin alone (0.5, 2.5, 5%) produced concentration‐dependent biphasic licking behavior of injured hind paw across 60 min and concentration‐dependent depression of voluntary wheel running for 7 consecutive days; (3) two‐week antibiotic treatment prior to formalin administration had a protective effect manifested as attenuation of Phase II formalin scores, and complete reversal of formalin pain‐depressed wheel running for 7 consecutive days; (4) the protective effects of vancomycin on formalin pain‐related outcomes were associated with divergent changes to proteobacteria in sedentary vs. voluntary exercised rats. These data indicate that a narrow spectrum gram‐positive antibiotic can have lasting protective effects on persistent pain‐related behaviors and that associated changes to gut microbiota vary as a function of sedentary vs. exercise condition. Parallel mechanistic studies are currently assessing the efficacy of probiotic and fecal microbiota transplant procedures vs. opioid compounds to block antibiotic‐induced modulation to formalin pain‐related outcomes.Support or Funding InformationThis research supported by a NIH COBRE grant (P20GM103643) that supports an animal behavior core facility, and a COBRE Pilot award and NIAMS R15 AREA grant (AR054975) to G.W.S.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.