Environmental enrichment and pain sensitivity; a study in maternally separated rats

Abstract

Rodents are highly dependent on maternal care after birth. Maternal separation (MS) is an animal model for studying neglect and abuse. Depriving the pup of such care renders the animal with Hypothalamic–Pituitary–adrenal (HPA) dysfunction and these animals are more susceptible to anxiety and stress as well as poor cognition. These effects are due to abnormal brain development in these animals. We have tried to investigate how maternal separation can affect pain sensation and whether a non‐pharmacological intervention such as enriched environment (EE) can restore an abnormal pain sensation. Animals were put into four groups MS, control (CTRL) and MS + EE and CTRL + EE groups that underwent EE after weaning until adulthood. These groups were tested for pain sensitivity with hot plate and tail flick for sensory pain and formalin for affect pain. The results showed that MS rats are more sensitive to pain in the hot plate test and formalin test, however, no significant difference was seen between groups for tail flick test. When MS rats experience EE their pain sensitivity is restored at the behavioral level. Further research is required to see how EE restores pain sensation in MS rats.

What are the consequences of Methylphenidate exposure for maternally separated rats?

“…In addition, MPH did not affect male group's pain threshold in both tail flick and hotplate. However, significant differences in sensory pain threshold are seen in adulthood for MS males relative to male controls (Mohtashami Borzadaran, Joushi, Taheri Zadeh, Sheibani, & Esmaeilpour, 2020). In addition, ELS (however with limited bedding protocol) led to changes in brain functional connectivity in both males and females (Dalaveri et al., 2017) and ELS animals showed a greater number of significant functional connections compared to controls when the pain circuit and associated regions were studied in adulthood (Holschneider, Guo, Mayer, & Wang, 2016).…”

Intergenerational effects of maternal separation on cognitive abilities of adolescent rats

“…From PND1‐PND21, MS litters were separated from dams for 180 min/day, starting at 08:30 AM and ending at 11:30 AM. MS dams were first removed from the home cage, after which the pups were moved to a cage in an incubator, which kept the temperature (30 ± 0.5°C, 52 ± 4% humidity) (Mohtashami Borzadaran et al., 2020) to avoid hypothermia. The dam was kept in a separate room for the duration of the separation to inhibit olfactory or ultrasound vocalization exchanges between dams and their pups.…”

The burden of early life stress on the nociceptive system development and pain responses

“…For thermal sensitivity, no differences were observed in many studies but hyposensitivities were also detected with the tail flick test (Coutinho et al, 2002), and the hot plate test (Weaver et al, 2007). Hypersensitivities were also seen with the hot plate (Genty et al, 2018b;Mohtashami Borzadaran et al, 2020) and the plantar test in rats (Juif et al, 2016;Melchior et al, 2018) and in mice with a similar method, a thermal analgesiometer (Fuentes et al, 2015;Pierce et al, 2014;Takatsuru et al, 2009).…”

“…On top of the altered baseline sensitivity to pain, MS induces long‐term altered sensibility to other pain‐triggering stimulation at adulthood, including neuropathic pain (Genty et al., 2018a; Mizoguchi et al., 2019; Nishinaka et al., 2015) and inflammatory pain induced either by formalin (Mohtashami Borzadaran et al., 2020; Uhelski & Fuchs, 2010), CFA (Vilela et al., 2017), or carrageenan (Melchior et al., 2018). The increased sensitivity to carrageenan‐induced inflammation has been explained by a deficit of the oxytocinergic anti‐hyperalgesic control and was prevented (as well as baseline mechanical and thermal sensitivity) by a neonatal OT treatment during the MS period.…”