Abstract
The influence of parental support on child pain experiences is well recognised. Accordingly, animal studies have revealed both short- and long-term effects of early life stress on nociceptive responding and neural substrates such as endocannabinoids. The endocannabinoid system plays an important role in mediating and modulating stress, social interaction, and nociception. This study examined the effects of maternal support or acute isolation on nociceptive responding of female rats to a range of stimuli during the juvenile pre-adolescent period and accompanying changes in the endocannabinoid system. The data revealed that juvenile female Sprague Dawley rats (PND21−24) isolated from the dam for 1 h prior to nociceptive testing exhibited increased latency to withdraw in the hot plate test and increased mechanical withdrawal threshold in the Von Frey test, compared to rats tested in the presence of the dam. Furthermore, isolated rats exhibited reduced latency to respond in the acetone drop test and enhanced nociceptive responding in the formalin test when compared to dam-paired counterparts. Anandamide, but not 2-AG, levels were reduced in the prefrontal cortex of dam-paired, but not isolated, juvenile rats following nociceptive testing. There was no change in the expression of CB1, FAAH or MAGL; however, CB2 receptor expression was reduced in both dam-paired and isolated rats following nociceptive testing. Taken together the data demonstrate that brief social isolation or the presence of the dam modulates nociceptive responding of juvenile rat pups in a modality specific manner, and suggest a possible role for the endocannabinoid system in the prefrontal cortex in sociobehavioural pain responses during early life.
Highlights
It is well recognised that parental presence during painful experiences can modulate a child’s responses to pain from the neonatal period through to adolescence [1,2,3]
The present study examined the effects of maternal presence versus absence on nociceptive responding to thermal heat, cold, mechanical and inflammatory noxious stimuli in juvenile female rat pups
Analysis of the sensitivity to mechanical stimuli during Von Frey testing revealed that isolated juvenile pups required heavier filaments to provoke a withdrawal response [t(18) = 3.74, p=0.002] (Fig. 1c), and demonstrated a significantly increased paw withdrawal threshold compared to dam-paired juvenile pups [t(18) = 4.15, p=0.0006] (Fig. 1d)
Summary
It is well recognised that parental presence during painful experiences can modulate a child’s responses to pain from the neonatal period through to adolescence [1,2,3]. Preclinical animal studies have manipulated dam-pup interactions during the first 2 weeks of life to model early-life stress [8,9], an effect which results in an array of physiological changes including altered nociceptive responding Several studies have demonstrated that short term (up to 30 min) isolation of neonatal rodent pups from the dam and siblings result in thermal hypoalgesia [12,13,14,15,16,17], while longer-term isolation (4–6h) is associated with either no change [16] or thermal hyperalgesia [18]. High levels of maternal care to pups following an early-life pain experience has been shown to result in reduced nociceptive responding (hypoalgesia) to thermal noxious stimuli in adulthood [19]. Social reunion between male, but not female adult sibling mice, following separation at weaning, has been shown to Abbreviations: 2-AG, 2-arachidonoylglycerol; AEA, anandamide; ADT, acetone drop test; CB1, cannabinoid receptor 1; CB2, cannabinoid receptor 2; CNS, central nervous system; CPS, composite pain score; FAAH, fatty acid amide hydrolase; HPT, hot plate test; MAGL, monoacylglycerol lipase; PFC, prefrontal cortex; VFT, Von Frey test
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