Analgesia for Early-Life Pain Prevents Deficits in Adult Anxiety and Stress in Rats

Abstract

Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this ‘hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a ‘hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants.

The long-term impact of early life pain on adult responses to anxiety and stress: Historical perspectives and empirical evidence

“…Across all studies, we consistently find that early life pain blunts adult sensitivity to acute anxiety- and stress-provoking stimuli (Victoria et al, 2013b; Victoria et al, 2015). Neonatally injured adults spend significantly more time in the center of the OF and display significantly longer latencies to immobility in the FST.…”

An examination of sex differences in the effects of early-life opiate and alcohol exposure

“…For example, neonatal inflammatory pain decreases locomotor activity in adult rats [64] and decreases pain sensitivity later in life, though more so in females than in males [65]. Neonatal pain also rapidly alters markers of pain and stress in the pup [66,67], and produces lifelong deficits in the response to stress in both male and female rats [68]. Thus, effective pain management in neonates is recognized as necessary and effective; and interestingly opiate administration at the time of inflammatory pain actually alleviates many of these negative effects described above.…”

“…Thus, effective pain management in neonates is recognized as necessary and effective; and interestingly opiate administration at the time of inflammatory pain actually alleviates many of these negative effects described above. Morphine administration at the time of neonatal injury can reverse decreased locomotor activity and alterations in pain sensitivity later in life [64,66]. In addition, analgesia for early-life pain prevents deficits in anxiety and stress in both male and female rats [66].…”

“…Morphine administration at the time of neonatal injury can reverse decreased locomotor activity and alterations in pain sensitivity later in life [64,66]. In addition, analgesia for early-life pain prevents deficits in anxiety and stress in both male and female rats [66]. Thus postnatal opiate administration is necessary and beneficial when administered either for NAS, surgery or severe pain.…”

Changes in Sleep Architecture under Sustained Pain in Adult Male Rats Subjected to Neonatal Short-Lasting Local Inflammatory Insult

“…One of the well-known animal models of early life pain is that of rat pups in the first week of life injected with carrageenan into the hind paw [1][2][3][4][5] . The effects on adult rats include generalized baseline hyposensitivity and increased evoked responses (hypersensitivity) after reinflammation of the previously injected paw.…”