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A Review of Strain and Sex Differences in Response to Pain and Analgesia in Mice.

ABSTRACT: Pain and its alleviation are currently a highly studied issue in human health. Research on pain and response to analgesia has evolved to include the effects of genetics, heritability, and sex as important components in both humans and animals. The laboratory mouse is the major animal studied in the field of pain and analgesia. Studying the inbred mouse to understand how genetic heritable traits and/or sex influence pain and analgesia has added valuable information to the complex nature of pain as a human disease. In the context of biomedical research, identifying pain and ensuring its control through analgesia in research animals remains one of the hallmark responsibilities of the research community. Advancements in both human and mouse genomic research shed light not only on the need to understand how both strain and sex affect the mouse pain response but also on how these research achievements can be used to improve the humane use of all research animal species. A better understanding of how strain and sex affect the response to pain may allow researchers to improve study design and thereby the reproducibility of animal research studies. The need to use both sexes, along with an improved understanding of how genetic heritability affects nociception and analgesic sensitivity, remains a key priority for pain researchers working with mice. This review summarizes the current literature on how strain and sex alter the response to pain and analgesia in the modern research mouse, and highlights the importance of both strain and sex selection in pain research.

SUBMITTER: Smith JC

PROVIDER: S-EPMC6935701 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A Review of Strain and Sex Differences in Response to Pain and Analgesia in Mice.

Smith Jennifer C JC

Comparative medicine 20191210 6

Pain and its alleviation are currently a highly studied issue in human health. Research on pain and response to analgesia has evolved to include the effects of genetics, heritability, and sex as important components in both humans and animals. The laboratory mouse is the major animal studied in the field of pain and analgesia. Studying the inbred mouse to understand how genetic heritable traits and/or sex influence pain and analgesia has added valuable information to the complex nature of pain a ...[more]

PMID: 31822324

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Project description:BackgroundA dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. These diseases often show a sex bias, suggesting sex differences in immune responses and in the intestinal microbiome. We hypothesized that sex differences in immune responses are associated with sex differences in microbiota composition.MethodsFecal microbiota composition (MITchip), mRNA expression in intestinal tissue (microarray), and immune cell populations in mesenteric lymph nodes (MLNs) were studied in male and female mice of two mouse strains (C57B1/6OlaHsd and Balb/cOlaHsd). Transcriptomics and microbiota data were combined to identify bacterial species which may potentially be related to sex-specific differences in intestinal immune related genes.ResultsWe found clear sex differences in intestinal microbiota species, diversity, and richness in healthy mice. However, the nature of the sex effects appeared to be determined by the mouse strain as different bacterial species were enriched in males and females of the two strains. For example, Lactobacillus plantarum and Bacteroides distasonis were enriched in B6 females as compared to B6 males, while Bifidobacterium was enriched BALB/c females as compared to BALB/c males. The strain-dependent sex effects were also observed in the expression of immunological genes in the colon. We found that the abundance of various bacteria (e.g., Clostridium leptum et rel.) which were enriched in B6 females positively correlated with the expression of several genes (e.g., Il-2rb, Ccr3, and Cd80) which could be related to immunological functions, such as inflammatory responses and migration of leukocytes. The abundance of several bacteria (e.g., Faecalibacterium prausnitzii et rel. and Coprobacillus et rel.- Clostridium ramosum et rel.) which were enriched in BALB/c males positively correlated to the expression of several genes (e.g., Apoe, Il-1b, and Stat4) related to several immunological functions, such as proliferation and quantity of lymphocytes. The net result was the same, since both mouse strains showed similar sex induced differences in immune cell populations in the MLNs.ConclusionsOur data suggests a correlation between microbiota and intestinal immune populations in a sex and strain-specific way. These findings may contribute to the development of more sex and genetic specific treatments for intestinal-related disorders.

Dataset Information

A Review of Strain and Sex Differences in Response to Pain and Analgesia in Mice.

Publications

A Review of Strain and Sex Differences in Response to Pain and Analgesia in Mice.

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