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Stress in the adult rat exacerbates muscle pain induced by early-life stress.

ABSTRACT: Early-life stress and exposure to stressful stimuli play a major role in the development of chronic widespread pain in adults. However, how they interact in chronic pain syndromes remains unclear.Dams and neonatal litters were submitted to a restriction of nesting material (neonatal limited bedding [NLB]) for 1 week. As adults, these rats were exposed to a painless sound stress protocol. The involvement of sympathoadrenal catecholamines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF?) in nociception was evaluated through behavioral and enzyme-linked immunosorbent assays, surgical interventions, and intrathecal antisense treatments.Adult NLB rats exhibited mild muscle hyperalgesia, which was markedly aggravated by sound stress (peaking 15 days after exposure). Adrenal medullectomy did not modify hyperalgesia in NLB rats but prevented its aggravation by sound stress. Sustained administration of epinephrine to NLB rats mimicked sound stress effect. Intrathecal treatment with antisense directed to IL-6 receptor subunit gp130 (gp130), but not to tumor necrosis factor receptor type 1 (TNFR1), inhibited hyperalgesia in NLB rats. However, antisense against either gp130 or TNFR1 inhibited sound stress-induced enhancement of hyperalgesia. Compared with control rats, NLB rats exhibit increased plasma levels of IL-6 but decreased levels of TNF?, whereas sound stress increases IL-6 plasma levels in control rats but not in NLB rats.Early-life stress induces a persistent elevation of IL-6, hyperalgesia, and susceptibility to chronic muscle pain, which is unveiled by exposure to stress in adults. This probably depends on an interaction between adrenal catecholamines and proinflammatory cytokines acting at muscle nociceptor level.

SUBMITTER: Alvarez P

PROVIDER: S-EPMC3760993 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Stress in the adult rat exacerbates muscle pain induced by early-life stress.

Alvarez Pedro P Green Paul G PG Levine Jon D JD

Biological psychiatry 20130521 9

<h4>Background</h4>Early-life stress and exposure to stressful stimuli play a major role in the development of chronic widespread pain in adults. However, how they interact in chronic pain syndromes remains unclear.<h4>Methods</h4>Dams and neonatal litters were submitted to a restriction of nesting material (neonatal limited bedding [NLB]) for 1 week. As adults, these rats were exposed to a painless sound stress protocol. The involvement of sympathoadrenal catecholamines interleukin 6 (IL-6) and ...[more]

PMID: 23706525

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Project description:Recently, the putative association between selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy and the development of social disorders in children has gained increased attention. However, clinical studies struggle with the confounding effects of maternal depression typically co-occurring with antidepressant treatment. Furthermore, preclinical studies using an animal model of maternal depression to study effects of perinatal SSRI exposure on offspring social behavior are limited. Therefore, the aim of this study was to investigate effects of perinatal fluoxetine exposure on juvenile and adult social behavior in male and female rat offspring, using an animal model of maternal vulnerability. We exposed heterozygous serotonin transporter (SERT) deficient female rats to early life maternal separation stress, and used this as a model for maternal vulnerability. Control and early life stressed heterozygous serotonin transporter knockout (SERT) dams were treated with the SSRI fluoxetine or vehicle throughout gestation and lactation. Subsequently, both male and female wildtype (SERT+/+) and heterozygous (SERT+/-) rat offspring were tested for pup ultrasonic vocalizations (USVs), juvenile social play behavior and adult social interaction. Fluoxetine treatment of the dams resulted in a reduced total USV duration in pups at postnatal day 6, especially in SERT+/+ males. Perinatal fluoxetine exposure lowered social play behavior in male offspring from both control and early life stressed dams. However, in females a fluoxetine-induced reduction in juvenile play behavior was only present in offspring from control dams. Offspring genotype did not affect juvenile play behavior. Despite fluoxetine-induced behavioral effects at juvenile age, fluoxetine reduced male adult social behavior in offspring from control dams only. Effects of fluoxetine on female adult social behavior were virtually absent. Interestingly, early life stress in dams increased adult social exploration in vehicle exposed SERT+/+ female offspring and total social behavior in fluoxetine exposed adult SERT+/- male offspring. Furthermore, SERT+/- males appeared less social during adulthood compared to SERT+/+ males. Overall, the present study shows that chronic blockade of the serotonin transporter by fluoxetine during early development has a considerable impact on pup USVs, juvenile social play behavior in both male and female offspring, and to a lesser extent on male social interaction in adulthood.

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Stress in the adult rat exacerbates muscle pain induced by early-life stress.

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Stress in the adult rat exacerbates muscle pain induced by early-life stress.

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