title: Preemptive analgesia I: physiological pathways and pharmacological modalities.
abstract: OBJECTIVE
  This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia.
  
  
  METHODS
  Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents.
  
  
  RESULTS
  The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (N-methyl-D-aspartate) - and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain.
  
  
  CONCLUSIONS
  The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.
authors.affiliation: Department of Anaesthesia, Cork University Hospital, Wilton, Cork, Ireland.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: M
authors.initials: M
authors.lastname: Ahmad
authors.forename: S J
authors.initials: SJ
authors.lastname: Brull
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000698:Analgesia / Q000379:methods*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000765:Anesthesia, Conduction; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D004525:Efferent Pathways / Q000502:physiology; D006801:Humans; D010146:Pain / Q000503:physiopathology; D010149:Postoperative Pain / Q000517:prevention & control*; D010465:Perception; D011292:Premedication; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D000317:Adrenergic alpha-Antagonists; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016194:Receptors, N-Methyl-D-Aspartate