title: Blockade of intra-articular adrenergic receptors increases analgesic demands for pain relief after knee surgery.
abstract: Activation of opioid receptors on peripheral sensory nerve terminals by opioid peptides that are produced and released from immune cells can result in inhibition of inflammatory pain. This study tests the hypothesis that postoperative pain is attenuated endogenously through a local sympathetic neurotransmitter-activated release of opioids in patients undergoing knee surgery. We examined the expression of opioid peptides and adrenergic receptors in cells infiltrating inflamed synovial tissue and we hypothesized that intra-articular (i.a.) administration of the adrenergic receptor antagonist labetalol will increase postoperative analgesic consumption and/or pain intensity in these patients. In a double-blind, randomized manner, 75 patients undergoing therapeutic knee arthroscopy received i.a. placebo (20 ml saline) or labetalol (2.5 or 5 mg in 20 ml saline) at the end of surgery. Postoperative pain intensity was assessed by visual analog and verbal rating scales at rest and on exertion, and by the consumption of morphine via patient-controlled analgesia. Synovial biopsies were taken during the operation for double-immunofluorescence confocal microscopy studies. Alpha(1)- and beta(2)-adrenergic receptors were co-expressed in opioid peptide-containing cells. No significant difference was seen in pain scores, but patients receiving 2.5 mg labetalol requested significantly higher amounts of morphine. These findings are consistent with the notion that surgical stress induces sympathetically activated release of endogenous opioids from inflammatory cells and subsequent analgesia via activation of peripheral opioid receptors.
authors.affiliation: Department of Anesthesiology, Landeskrankenhaus Klagenfurt, Klagenfurt, Austria.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kager
authors.forename: Shaaban A
authors.initials: SA
authors.lastname: Mousa
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
authors.forename: Christoph
authors.initials: C
authors.lastname: Stein
authors.forename: W
authors.initials: W
authors.lastname: Pipam
authors.forename: Rudolf
authors.initials: R
authors.lastname: Likar
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular / Q000379:methods; D007718:Knee Injuries / Q000378:metabolism / Q000601:surgery*; D007741:Labetalol / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy* / Q000378:metabolism; D055815:Young Adult
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D000700:Analgesics; D007741:Labetalol
references.citation: Brain Res Rev. 2009 Apr;60(1):90-113
references.pmid: 19150465
references.citation: Brain Behav Immun. 2002 Dec;16(6):799-807
references.pmid: 12480508
references.citation: Nat Med. 2003 Aug;9(8):1003-8
references.pmid: 12894165
references.citation: J Cardiovasc Pharmacol. 1986 Jan-Feb;8(1):44-50
references.pmid: 2419691
references.citation: Pharmacol Rev. 2000 Dec;52(4):595-638
references.pmid: 11121511
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7664-7
references.pmid: 10393877
references.citation: Lancet. 1993 Aug 7;342(8867):321-4
references.pmid: 8101583
references.citation: Pharmacol Rev. 2003 Mar;55(1):1-20
references.pmid: 12615951
references.citation: J Neuroimmunol. 2003 Aug;141(1-2):30-9
references.pmid: 12965251
references.citation: Nat Med. 1998 Dec;4(12):1425-8
references.pmid: 9846582
references.citation: Arthritis Rheum. 2000 Sep;43(9):1905-15
references.pmid: 11014340
references.citation: J Rheumatol. 2001 Oct;28(10):2176-83
references.pmid: 11669152
references.citation: Endocrinology. 2004 Mar;145(3):1331-41
references.pmid: 14630714
references.citation: Adv Exp Med Biol. 2003;521:148-60
references.pmid: 12617572
references.citation: J Clin Invest. 1996 Aug 1;98(3):793-9
references.pmid: 8698872
references.citation: Pain. 1999 Dec;83(3):525-532
references.pmid: 10568861
references.citation: J Clin Invest. 2008 Mar;118(3):1065-73
references.pmid: 18246198
references.citation: Br J Anaesth. 2004 Sep;93(3):375-80
references.pmid: 15247115
references.citation: J Rheumatol. 1990 Dec;17(12):1592-9
references.pmid: 1707460
references.citation: J Rheumatol. 2000 Nov;27(11):2558-65
references.pmid: 11093434
references.citation: J Rheumatol. 2002 Mar;29(3):427-35
references.pmid: 11908553
references.citation: Pain. 2002 Aug;98(3):269-275
references.pmid: 12127028
references.citation: Anesth Analg. 1997 Jun;84(6):1313-7
references.pmid: 9174312
references.citation: J Neuroimmunol. 2007 Feb;183(1-2):133-45
references.pmid: 17223201
references.citation: Eur J Neurosci. 2004 Jul;20(1):92-100
references.pmid: 15245482
references.citation: Ann Rheum Dis. 2007 Jul;66(7):871-9
references.pmid: 17324971
references.citation: J Clin Invest. 1997 Jul 1;100(1):142-8
references.pmid: 9202066
references.citation: Anesthesiology. 2004 Jun;100(6):1573-81
references.pmid: 15166580
references.citation: Auton Autacoid Pharmacol. 2002 Feb;22(1):29-35
references.pmid: 12423424