Neonatal pain and stress disrupts later‐life pavlovian fear conditioning and sensory function in rats: Evidence for a two‐hit model

Abstract

Early life trauma has been linked to increased risks for anxiety, depression, and chronic pain. We used rodent models of acute and inflammatory neonatal pain to explore effects on fear conditioning and somatosensory function. Hindpaw needle pricks or handling on postnatal days (PNDs) 1-7 caused lasting impacts on affective and somatosensory function when assessed at later ages, PNDs 24 (postweaning), 45 (adolescence), or 66 (adulthood). First, auditory, but not contextual, freezing was mildly disrupted regardless of age. Second, a profound postfear conditioning tactile hypersensitivity was observed in neonatally stressed, postweaning rats. In the absence of fear conditioning, the mechanical hypersensitivity was not observed, consistent with a two-hit model of psychopathology. Injections of 2% α-carrageenan did not have the same lasting impact but was slightly protective against observed effects of neonatal vehicle injections. Basal and elicited corticosterone levels postweaning were not altered by neonatal pain or handling. These data demonstrate that neonatal adversity can have lasting impacts on affective and somatosensory function that differs regardless of age.

Development of Threat Expression Following Infant Maltreatment: Infant and Adult Enhancement but Adolescent Attenuation

“…With further physical and cognitive maturation, pups leave the mother and responding to threat is completely independent: here, we explore adolescent (PN45) and adult responses to provide a lifespan assessment. This complements research from other labs, as well as our own, studying threat conditioning across development (Pattwell et al, 2011; Li et al, 2012; Cowan et al, 2013; Poulos et al, 2014; Hartley and Lee, 2015; Madsen and Kim, 2016; Bucci and Stanton, 2017; Tallot et al, 2017; Davis et al, 2018).…”

Repetitive Pain in Neonatal Male Rats Impairs Hippocampus-Dependent Fear Memory Later in Life

“…Until now, there have been a few published reports addressing the relationship between early-life pain and later-life fear memory. Davis’s work ( Davis et al, 2018 ) found that needle prick produced a disruption in auditory fear conditioning when collapsed across age and sex. However, it did not show any difference in the training context and novel context.…”

Adverse Behavioral Changes in Adult Mice Following Neonatal Repeated Exposure to Pain and Sucrose

“…That is, inflammatory pain or pain from injections may not have the same consequences as superficial needle-pricks. Our relatively innocuous needle-prick pain stimulus is an important difference, given that we used very thin needles (30G) and did not penetrate deeper layers, such as tendon or bone, in contrast to the more invasive procedures used in needle-prick pain in previous rat studies (Anand et al, 1999; Davis et al, 2018).…”

“…Parallel to our findings on long-term memory impairment of early pain exposure, Henderson and colleagues showed that even a single injection of formalin in the hindpaw of infant rats at birth altered hippocampal-dependent memory in adulthood (Henderson et al, 2015). A study in rat pups exposed to four daily hindpaw needle-pricks (24G) or slight touch during the first 7 days of life showed effects on fear conditioning (auditory freezing only) at post-weaning, adolescence, and adulthood ages (i.e., Ps 24, 45, 66) (Davis et al, 2018). Similar to our findings, they failed to show an effect on long-term sensory thresholds unless rats were exposed to fear conditioning prior to testing.…”