The combination of postnatal maternal separation and social stress in young adulthood does not lead to enhanced inflammatory pain sensitivity and depression-related behavior in rats.

Julien Genty,Fernand Anton,Ulrike Hanesch,Milène Tetsi Nomigni

doi:10.1371/journal.pone.0202599

Abstract

The cumulative and match/mismatch hypotheses of stress are still under discussion regarding the effects of early life stress (ELS) on the vulnerability or resilience to psychopathology. In this context, an additional stress in later life (second hit) often leads to stress-related disorders that frequently include comorbid pain states. We previously observed that maternal separation (MS), a model of ELS, reduces vulnerability to neuropathic and inflammatory pain in rats. In the present study, we investigated the effects of an additional later stressor on the vulnerability to inflammatory pain. Sprague Dawley pups were divided into 4 groups: controls (CON, no stress), MS, social stress (SS) and MS+SS. At young adult age (from 7 to 15 weeks), stress- as well as pain-related parameters were evaluated prior and during 21 days following the induction of paw inflammation with complete Freund’s adjuvant (CFA). Finally spinal glutamatergic transmission, immunocompetent cells, pro-inflammatory cytokines and growth factors were examined using qPCR. None of the stress conditions had a significant impact on corticosterone levels and anhedonia. In the forced swim test, MS and SS displayed increased passive coping whereas the combination of both stressors revoked this effect. The different stress conditions had no influence on basal mechanical thresholds and heat sensitivity. At 4 days post-inflammation all stress groups displayed lower mechanical thresholds than CON but the respective values were comparable at 7, 10, and 14 days. Only on day 21, MS rats were more sensitive to mechanical stimulation compared to the other groups. Regarding noxious heat sensitivity, MS+SS animals were significantly less sensitive than CON at 10 and 21 days after CFA-injection. qPCR results were mitigated. Despite the finding that stress conditions differentially affected different players of glutamatergic transmission, astrocyte activity and NGF expression, our biochemical results could not readily be related to the behavioral observations, precluding a congruent conclusion. The present results do neither confirm the cumulative nor corroborate or disprove the match/mismatch hypothesis.

Highlights

While chronic stress often leads to deleterious effects, it may trigger adaptive changes that can possibly be beneficial
The group that was assigned to maternal separation (MS)+SS conditions unexpectedly showed a significantly lower sucrose preference as compared to control animals (CON) (p
The post hoc analysis revealed a significant increase of immobility in the MS (178.21 ± 6.42 s; p

Summary

Introduction

While chronic stress often leads to deleterious effects, it may trigger adaptive changes that can possibly be beneficial. In this context, a major research emphasis was recently put on the long-term consequences of early life stress (ELS) for the processing of novel stress exposure in the course of adulthood. In the cumulative stress hypothesis early exposure to stressors is regarded as detrimental. The inoculation hypothesis states that early exposure to stressors leads to a better coping. The match/mismatch theory states that beneficial consequences may be expected if individuals are exposed to similar (matching) adversities in adulthood while a mismatching environment may lead to enhanced vulnerability for psychopathologies [2]

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