%0 Journal Article
%T Sestrin2 prevents neonatal incision pain and re-incision enhanced hyperalgesia in adult rats.
%A Shi X
%A Wang C
%A Zhao T
%A Gu M
%A Yang J
%A Sun N
%A Huang Y
%A Yao Y
%A Yu L
%A Yan M
%J Brain Res
%V 1805
%N 0
%D 04 2023 15
%M 36801208
%F 3.61
%R 10.1016/j.brainres.2023.148287
%X Improving the methods for recognizing pain is important for infants admitted to the neonatal intensive care unit. Sestrin2 is a novel stress-inducible protein with a neuroprotective role that functions as a molecular mediator of hormesis. Nevertheless, the role of sestrin2 in the pain process is still unclear. The following study examined the role of sestrin2 on mechanical hypersensitivity after pups incision, as well as enhanced pain hyperalgesia after adulthood re-incision in rats.<BR>The experiment was divided into two parts: (1) studying the effect of sestrin2 in the neonatal incision; (2) studying the priming effect in adulthood re-incision. An animal model was established in seven-day-old rat pups with a right hind paw incision. Pups were intrathecally administrated rh-sestrin2 (exogenous sestrin2). Paw withdrawal threshold testing was performed to assay mechanical allodynia; tissue was analyzed in ex vivo using Western blot and immunofluorescence. SB203580 was further used to inhibit microglial function and evaluate the sex-dependent effect in adulthood.<BR>Sestrin2 expression increased transitorily in the spinal dorsal horn in pups after incision. Administration of rh-sestrin2 improved pups' mechanical hypersensitivity by regulating the AMPK/ERK pathway and alleviated re-incision-induced enhanced hyperalgesia in male and female adult rats. After administration of SB203580 in pups, the mechanical hyperalgesia following re-incision in adult rats was prevented in males but not females; however, the protective effect of SB203580 in males was counteracted by silencing sestrin2.<BR>These data suggest that sestrin2 prevents neonatal incision pain and re-incision enhanced hyperalgesia in adult rats. Moreover, microglia inhibition affects enhanced hyperalgesia only in adult males, which may be regulated through the sestrin2 mechanism. To sum up, these sestrin2 data may be a potential common molecular target for treating re-incision hyperalgesia in different sexes.