Postoperative pain management and proinflammatory cytokines: Animal and human studies

Yehuda Shavit*, Keren Fridel, Benzion Beilin

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The postoperative period is associated with neuroendocrine, metabolic, and immune alterations, which are the combined result of tissue damage, anesthesia, postoperative pain, and psychological stress. Limited evidence indicates that pain management in the postoperative period can affect the outcome of the surgery, reducing cardiac, pulmonary, and metabolic complications. Recent evidence indicates that pain and immune factors, especially proinflammatory cytokines, mutually interact and influence each other. A series of animal studies demonstrates that effective preemptive analgesia improved postoperative recovery, and this effect was enhanced by coadministration of IL-1ra together with the preemptive analgesics. Furthermore, preemptive analgesia attenuated surgery-induced PGE2 production in the amygdala and the activation of the HPA axis. IL-1 signaling is required for the production of amygdala PGE2 in response to surgical stress, and may thus affect the physiological and psychological aspects of surgical stress. These reports suggest that short-term effective analgesia can have long-lasting beneficial effects on surgery recovery. They further suggest that IL-1 blockade should be considered in the clinical management of pain associated with peripheral or nerve injury. Another series of human studies describes an interaction between the effectiveness of postoperative pain relief and surgery-associated immune alterations: In three separate studies, the more effective pain management technique was associated with diminished surgery-induced immune alterations, especially diminished elevation of IL-1. Reduced elevation of postoperative IL-1 and effective pain relief may both contribute to an attenuated illness response and a better surgery outcome.

Original languageEnglish
Pages (from-to)443-451
Number of pages9
JournalJournal of NeuroImmune Pharmacology
Issue number4
StatePublished - Dec 2006
Externally publishedYes


  • Local anesthetics
  • Morphine
  • Neuroendocrine
  • Physostigmine
  • Postoperative pain
  • Preemptive analgesia
  • Proinflammatory cytokines


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