Effects of surgical stress on brain prostaglandin E2 production and on the pituitary-adrenal axis: Attenuation by preemptive analgesia and by central amygdala lesion

Yehuda Shavit, Joseph Weidenfeld, Freda G. Dekeyser, Gila Fish, Gilly Wolf, Eduard Mayburd, Ylia Meerson, Benzion Beilin

Research output: Contribution to journalArticlepeer-review

Abstract

Surgical stress is the combined result of tissue injury, anesthesia, and postoperative pain. It is characterized by elevated levels of adrenocorticotropin (ACTH), corticosterone (CS), and elevated levels of prostaglandin E2 (PGE2) in the periphery and in the spinal cord. The present study examined the effects of perioperative pain management in rats undergoing laparotomy on serum levels of ACTH, CS, and on the production of PGE2 in several brain regions, including the amygdala. The amygdala is known to modulate the pituitary-adrenal axis response to stress. We, therefore, also examined the effects of bilateral lesions in the central amygdala (CeA) on laparotomy-induced activation of the pituitary-adrenal axis in rats. In the first experiment, rats either underwent laparotomy or were not operated upon. Half the rats received preemptive analgesia extended postoperatively, the other received saline. ACTH, CS serum levels, and ex vivo brain production of PGE2 were determined. In the second experiment, rats underwent bilateral lesions of the CeA. Ten days later, rats underwent laparotomy, and ACTH and CS serum levels were determined. Laparotomy significantly increased amygdala PGE2 production, and CS and ACTH serum levels. This elevation was markedly attenuated by perioperative analgesia. Bilateral CeA lesions also attenuated the pituitary-adrenal response to surgical stress. The present findings suggest that the amygdala plays a regulatory role in mediating the neuroendocrine response to surgical stress. Effective perioperative analgesia attenuated the surgery-induced activation of pituitary-adrenal axis and PGE2 elevation. The diminished elevation of PGE2 may suggest a mechanism by which pain relief mitigates pituitary-adrenal axis activation.

Original languageEnglish
Pages (from-to)10-17
Number of pages8
JournalBrain Research
Volume1047
Issue number1
DOIs
StatePublished - 14 Jun 2005
Externally publishedYes

Keywords

  • ACTH
  • Amygdala
  • Corticosterone
  • Local anesthetics
  • Morphine
  • Preemptive analgesia
  • Prostaglandins

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