Effects of Intrathecal Administration of Prostaglandin-D2 on Stress-Induced Analgesia: Involvements of DP2 Receptors

Abstract

Prostaglandin D₂ is the most abundant prostaglandin in the mammalian brain. Exposure to stressful stimuli is often accompanied by reduced pain sensitivity, termed “stress-induced analgesia” (SIA). In the present study, the possible modulatory role of prostaglandin-D2 (PGD2) in the acute or chronic type of SIA was examined in male and female rats. Acute and chronic (long-term) restraint stress (RS) in male and female rats was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. The involvements of specific PGD2 receptors in the modulatory role of PGD2 on SIA also investigated by specific antagonists (DP1 or DP2). Corticosterone levels were assessed in groups of rats following exposure to stress. Acute or chronic restraint stress altered formalin-induced spontaneous behaviors in male and female rats. Furthermore, intrathecal microinjection of PGD2 (10 µg/mL) could reverse acute SIA in male but not in female rats. DP2 antagonist of PGD2 (CAY10471) attenuated pain score in the acute RS-induced analgesia in male rats. Administration of PGD2 increases the phospho-extracellular signal regulated kinase 2 (pERK2) levels in the spinal cord of male RS rats. Sex differences were also seen in plasma corticosterone concentrations post injection of PGD2 in acute SIA in male rats. The outcome suggests that not only central microinjection of PGD2 could attenuate acute SIA in male rats, but also its antagonist could turn over this effect.