Low maternal licking/grooming stimulation increases pain sensitivity in male mouse offspring

Abstract

Deprivation of maternal care has been associated with higher pain sensitivity in offspring. In the present study, we hypothesized that the maternal licking/grooming behavior was an important factor for the development of the pain regulatory system. To test this hypothesis, we used male F2 offspring of early-weaned (EW) F1 mother mice that exhibit lower frequency of licking/grooming behavior. The formalin test revealed that F2 offspring of EW F1 dams showed significantly higher pain behavior than F2 offspring of normally-weaned (NW) F1 dams. We found that the mRNA levels of transient receptor potential vanilloid 1 (TRPV1), a nociceptor, were higher in the lumbosacral dorsal root ganglion (DRG) of F2 offspring of EW F1 dams than those of F2 offspring of NW F1 dams, suggesting that the higher pain sensitivity may be attributed to low licking/grooming, which may result in developmental changes in nociceptive neurons. In the DRG, mRNA levels of Mas-related G-protein coupled receptor B4 (MrgprB4), a marker of sensory neurons that detect gentle stroking, was also up-regulated in the F2 offspring of EW F1 dams. Considering that gentle touch alleviates pain, Mrgprb4 up-regulation may reflect a compensatory change. The present findings indicate important implications of maternal licking/grooming behavior in the development of the pain regulatory system.

Intergenerational transmission of maternal behavioral traits in mice: involvement of the gut microbiota

“…In both Experiments 1 and 2, the ANOVA for EW-F1 and NW-F1 mothers indicated that the LG expression of both mothers decreased with postpartum days, but LG expression in EW-F1 mice was consistently lower than that in NW-F1 mice from postnatal days 1 to 9. These results suggested that, similar to the findings of our previous studies ( Kikusui et al, 2005 ; Sakamoto et al, 2021 ), mouse mothers experiencing early weaning had lower LG expression than mothers who experienced normal weaning. In Experiment 1, ANOVA for F2 mice also indicated that the LG expression of EW-F2 mice was lower than that of NW-F2 mice, although both F2 mice were weaned normally, similar to the observation for F1 mice.…”

“…Behaviorally, rat offspring of low-LG mothers have been shown to exhibit high anxiety ( Caldji et al, 1998 ). In mice, we have previously revealed that the offspring of EW mothers are hypersensitive to pain ( Sakamoto et al, 2021 ) and skin development is also affected, with high resistance to skin barrier disruption ( Sakamoto et al, 2019 ). As these phenotypes are necessary for survival in harsh environments, the intergenerational transmission of maternal LG traits may be one of the strategies by which rodent species adapt to their environment.…”

“…The procedure used to obtain EW mice (F1) was the same as that described in our previous studies ( Mogi et al, 2016 ; Sakamoto et al, 2021 ). Pregnant female mice were monitored daily until parturition.…”

“…We have previously demonstrated that mouse pups can distinguish between their own mother and an alien mother and that mothers can also differentiate their own pups from alien pups ( Mogi et al, 2017 ), thereby suggesting the existence of mother–infant bonding. Furthermore, as a result of the deprivation of mother–infant bonding owing to early weaning, early weaned (EW) F1 mother mice showed a lower frequency of LG in their own pups than the normally weaned (NW) F1 mother mice ( Kikusui et al, 2005 ; Sakamoto et al, 2021 ). In this study, we compared maternal behavior between F2 offspring of EW F1 mothers (EW-F2 offspring) and F2 offspring of NW F1 mothers (NW-F2 offspring).…”

Delayed Formation of Neonatal Reflexes and of Locomotor Skills Is Associated with Poor Maternal Behavior in OXYS Rats Prone to Alzheimer’s Disease-like Pathology

“…One of the body’s systems most vulnerable to external factors is the central nervous system, which controls the workings of the body as a whole. There is good evidence that maternal licking and grooming have a strong impact on the development of emotional and cognitive behavior later in life [ 8 , 9 ]. Natural differences in maternal care among rats have been shown to predict subsequent changes in spatial and emotional learning and memory, anxiety, social behavior, exploratory activity, and stress reactivity [ 10 , 11 , 12 , 13 , 14 , 15 ].…”