Altered nociceptive, endocrine, and dorsal horn neuron responses in rats following a neonatal immune challenge

Zouikr, Ihssane; Tadros, Melissa A; Barouei, Javad; Beagley, Kenneth W.; Clifton, Vicki L.; Callister, Robert J.; Hodgson, Deborah M.

doi:10.1016/j.psyneuen.2013.11.016

Cited by 24 publications

(51 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously demonstrated that neonatal LPS exposure exerts developmentally regulated changes in formalin-induced behaviours, corticosterone levels, and dorsal horn neuronal properties with pronounced changes observed particularly at PND 22 [10]. In the present study, we aim to determine the supra-spinal changes associated with the neonatal immune challenge in PND 22 rats.…”

Section: Introductionmentioning

confidence: 89%

“…Exposure to LPS during perinatal life is an established model of early life immune stress [7]–[10]. Our laboratory and others have demonstrated that neonatal LPS exposure alters immune and neuroendocrine function later in life [11]–[13].…”

Section: Introductionmentioning

confidence: 97%

“…Interestingly, we recently demonstrated that neonatal LPS exposure can also affect inflammatory pain responses, as indicated by enhanced susceptibility to formalin-induced flinching in LPS-challenged preadolescent rats [10]. We have also shown that LPS-induced behavioural hyperalgesia observed at postnatal day (PND) 22 is accompanied by increased plasma corticosterone responses and changes in the intrinsic properties of spinal dorsal horn neurons [10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Altered Formalin-Induced Pain and Fos Induction in the Periaqueductal Grey of Preadolescent Rats following Neonatal LPS Exposure

et al. 2014

Self Cite

View full text Add to dashboard Cite

Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process.

show abstract

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Altered Formalin-Induced Pain and Fos Induction in the Periaqueductal Grey of Preadolescent Rats following Neonatal LPS Exposure

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Executive functions in children born very preterm have been identified as an area of difficulty in this population, even when intelligence is broadly normal (Mulder et al, 2009; Aarnoudse-Moens et al, 2012). One primary mechanism underling early programming effects of stress is re-setting of the hypothalamic-pituitary-adrenal (HPA) axis, reflected by long-term changes in cortisol the primary stress hormone in humans (Brummelte et al, 2012; Grunau, 2007; Grunau, 2013; Zouikr et al, 2014). Early exposure to stress has been shown to have prolonged effects on cognitive and affective functions (Richards and Wadsworth, 2004; Heim and Nemeroff, 2002; Heim et al, 2008); reviewed by (Lupien et al, 2009; Pechtel and Pizzagalli, 2011).…”

Section: Introductionmentioning

confidence: 99%

The Val66Met brain-derived neurotrophic factor gene variant interacts with early pain exposure to predict cortisol dysregulation in 7-year-old children born very preterm: Implications for cognition

et al. 2017

View full text Add to dashboard Cite

Early stress in the form of repetitive neonatal pain, in infants born very preterm, is associated with long-term dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and with poorer cognitive performance. Brain-derived neurotrophic factor (BDNF) which is important in synaptic plasticity and cognitive functions is reduced by stress. Therefore the BDNF Val66Met variant, which affects secretion of BDNF, may interact with early exposure to pain-related stress in children born very preterm, to differentially affect HPA regulation that in turn may be associated with altered cognitive performance. The aims of this study were to investigate whether in children born very preterm, the BDNF val66met variant modulates the association between neonatal pain-related stress and cortisol levels at age 7 years, and if cortisol levels were related to cognitive function. Furthermore, we examined whether these relationships were sex-specific. Using a longitudinal cohort design, N=90 children born very preterm (24–32 weeks gestation) were followed from birth to age 7 years. Cortisol was assayed from hair as an index of cumulative stress and from saliva to measure reactivity to a cognitive challenge. BDNF Val66Met variant was genotyped at 7 years using real time PCR. Using generalized linear modeling, in boys with the Met allele, greater neonatal pain-related stress (adjusted for clinical risk factors) predicted lower hair cortisol (p=0·006) and higher reactivity salivary cortisol (p=0.002). In both boys and girls with the Met allele, higher salivary cortisol reactivity was correlated with lower IQ (r= −0.60; p=0.001) and poorer visual-motor integration (r= −0.48; p=0.008). Our findings show associations between lower BDNF availability (presence of the Met allele) and vulnerability to neonatal pain/stress in boys, but not girls. This exploratory study suggests new directions for research into possible mechanisms underlying how neonatal pain/stress is related to cognitive performance in children born very preterm.

show abstract

“…Establishing the underlying circuits requires a complex developmental plan that is first laid down in the embryo, consolidated in the fetus, and modified throughout life (Fitzgerald 2005;Petersson et al 2003). Moreover, when this complex developmental plan is interrupted, it can result in adverse consequences for sensorimotor processing in the adult (Baccei 2010;Walker et al 2009;Zouikr et al 2014). Our understanding of the important developmental changes that occur in the early stages of spinal cord development come largely from studies in rodents.…”

mentioning

confidence: 99%

Electrical maturation of spinal neurons in the human fetus: comparison of ventral and dorsal horn

Tadros

Lim

Hughes

et al. 2015

Journal of Neurophysiology

View full text Add to dashboard Cite

-The spinal cord is critical for modifying and relaying sensory information to, and motor commands from, higher centers in the central nervous system to initiate and maintain contextually relevant locomotor responses. Our understanding of how spinal sensorimotor circuits are established during in utero development is based largely on studies in rodents. In contrast, there is little functional data on the development of sensory and motor systems in humans. Here, we use patch-clamp electrophysiology to examine the development of neuronal excitability in human fetal spinal cords (10 -18 wk gestation; WG). Transverse spinal cord slices (300 m thick) were prepared, and recordings were made, from visualized neurons in either the ventral (VH) or dorsal horn (DH) at 32°C. Action potentials (APs) could be elicited in VH neurons throughout the period examined, but only after 16 WG in DH neurons. At this age, VH neurons discharged multiple APs, whereas most DH neurons discharged single APs. In addition, at 16 -18 WG, VH neurons also displayed larger AP and after-hyperpolarization amplitudes than DH neurons. Between 10 and 18 WG, the intrinsic properties of VH neurons changed markedly, with input resistance decreasing and AP and after-hyperpolarization amplitudes increasing. These findings are consistent with the hypothesis that VH motor circuitry matures more rapidly than the DH circuits that are involved in processing tactile and nociceptive information. action potential; excitability; pain; motoneuron THE ABILITY TO INTERACT APPROPRIATELY with our environment arises, in part, from the capacity of the spinal cord to receive, modify, and relay sensory information and respond to this information via motor commands that produce coordinated movement.

show abstract

Altered nociceptive, endocrine, and dorsal horn neuron responses in rats following a neonatal immune challenge

Cited by 24 publications

References 43 publications

Altered Formalin-Induced Pain and Fos Induction in the Periaqueductal Grey of Preadolescent Rats following Neonatal LPS Exposure

Altered Formalin-Induced Pain and Fos Induction in the Periaqueductal Grey of Preadolescent Rats following Neonatal LPS Exposure

The Val66Met brain-derived neurotrophic factor gene variant interacts with early pain exposure to predict cortisol dysregulation in 7-year-old children born very preterm: Implications for cognition

Electrical maturation of spinal neurons in the human fetus: comparison of ventral and dorsal horn

Contact Info

Product

Resources

About