Involvement of intra-articular corticotropin-releasing hormone in postoperative pain modulation.
OBJECTIVE
Opioid receptors are expressed on peripheral nerve endings and opioid peptides (beta-endorphin, END) are produced in various immune cells of synovial tissue after knee trauma. Because corticotropin-releasing hormone (CRH) acts through its receptors on END-containing immune cells, this randomized controlled trial investigated whether the intra-articular (IA) injection of CRH reduces postoperative pain intensity and supplemental analgesic consumption in patients undergoing arthroscopic knee surgery.


METHODS
Patients were randomly assigned to one of the following IA and IV treatments: group saline (SAL) (n=17) received isotonic SAL IA and 10 microg CRH IV; group CRH (n=16) received 10 microg CRH IA and SAL IV; group CNL (n=18) received 10 microg CRH plus 0.12 mg naloxone IA and SAL IV. Patients pain intensity at rest and during exercise, cortisol plasma concentrations as well as supplemental analgesics were documented. Immunohistochemistry analyzed colocalization of CRH receptors and END.


RESULTS
IA but not IV CRH resulted in a significant but short lasting reduction of postoperative pain under both resting and exercise conditions without changes in cortisol plasma concentrations. Coadministration of naloxone reversed this pain reduction under resting but not exercise conditions. The majority of CRH receptor expressing cells contained END within synovial tissue.


CONCLUSIONS
In conclusion, this first clinical trial provides preliminary evidence for a short but not robust analgesic effect of a single dose of IA CRH in patients undergoing arthroscopic knee surgery. Further clinical studies will have to examine different doses of IA CRH-induced analgesia and to support the involvement of opioid peptides.
Likar
Rudolf
R
Abteilung für Anaesthesiologie und Intensivmedizin, LKH Klagenfurt, St Veiter-Strasse 47, A-9020 Klagenfurt, Austria.
Mousa
Shaaban A
SA
Steinkellner
Hermann
H
Koppert
Wolfgang
W
Philippitsch
Gudrun
G
Stein
Christoph
C
Schäfer
Michael
M
D000328:Adult; D000368:Aged; D001182:Arthroscopy; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D015444:Exercise; D006728:Hormones / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D007270:Injections, Intra-Articular; D007275:Injections, Intravenous; D007718:Knee Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage / Q000627:therapeutic use; D010149:Postoperative Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D012146:Rest; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D001615:beta-Endorphin / Q000378:metabolism
D004338:Drug Combinations; D006728:Hormones; D018019:Receptors, Corticotropin-Releasing Hormone; D009270:Naloxone; D001615:beta-Endorphin; D003346:Corticotropin-Releasing Hormone