Evaluation of menstrual cycle effects on morphine and pentazocine analgesia.
Studies have demonstrated menstrual cycle influences on basal pain perception, but direct evidence of menstrual cycle influences on analgesic responses has not been reported in humans. Our aim was to determine whether the magnitude of morphine and pentazocine analgesia varied across the menstrual cycle. Sixty-five healthy women, 35 taking oral contraceptives (OC) and 30 normally cycling (NOC), underwent experimental pain assessment both before and after intravenous administration morphine (0.08mg/kg) or pentazocine (0.5mg/kg) compared to saline placebo. Both active drug and placebo were administered once during the follicular phase and once during the luteal phase. Measures of heat, ischemic, and pressure pain sensitivity were obtained before and after drug administration. Change scores in pain responses were computed to determine morphine and pentazocine analgesic responses, and medication side effects were recorded. The data were analyzed using mixed-model analyses of variance. NOC women showed slightly greater heat pain sensitivity in the follicular vs luteal phase, while the reverse pattern emerged for OC women (P=0.046). Also, OC women showed lower pressure pain thresholds compared to NOC women (P<0.05). Regarding analgesic responses, NOC women showed greater morphine analgesia for ischemic pain during the follicular vs the luteal phase (P=0.004). Likewise, side effects for morphine were significantly higher in NOC women in the follicular phase than in the luteal phase (P=0.02). These findings suggest that sex hormones may influence opioid responses; however, the effects vary across medications and pain modalities and are likely to be modest in magnitude. Limited menstrual cycle effects on baseline pain responses were observed; however, morphine analgesia and side effects were greater during the follicular phase.
Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville, FL 32610-3628, USA North Florida/South Georgia Veterans Health System, Gainesville, FL 32608-1197, USA Department of Gynecology, College of Medicine, University of Florida, Gainesville, FL 32610-0221, USA Division of Rheumatology & Clinical Immunology, College of Medicine, University of Florida, Gainesville, FL 32610-0221, USA.
M C
MC
Ribeiro-Dasilva
R M
RM
Shinal
T
T
Glover
R S
RS
Williams
R
R
Staud
J L
JL
Riley
R B
RB
Fillingim
D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D008597:Menstrual Cycle / Q000187:drug effects*; D009020:Morphine / Q000627:therapeutic use*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects*; D010423:Pentazocine / Q000627:therapeutic use*; D013223:Statistics as Topic; D055815:Young Adult
D000701:Analgesics, Opioid; D012739:Gonadal Steroid Hormones; D009020:Morphine; D010423:Pentazocine
Pain. 2010 Oct;151(1):61-68
20692097
Clin J Pain. 2003 May-Jun;19(3):175-86
12792556
Clin Exp Pharmacol Physiol. 1995 May;22(5):342-4
7554425
J Pain. 2006 Mar;7(3):151-60
16516820
J Neurosci. 2002 Jun 15;22(12):5100-7
12077205
Neuroscience. 2006 Dec;143(3):885-93
17008018
Neurosci Biobehav Rev. 2000 May;24(3):375-89
10781697
Can J Anaesth. 1991 Oct;38(7):876-9
1835905
BMJ. 2006 Apr 1;332(7544):749-55
16484239
Drug Alcohol Depend. 2001 Aug 1;63(3):215-28
11418226
Pain. 2007 Nov;132 Suppl 1:S26-S45
17964077
Am J Physiol. 1990 Dec;259(6 Pt 2):R1156-63
2260726
J Pain. 2005 Apr;6(4):261-74
15820914
Pain. 2003 Jun;103(3):285-302
12791435
Can J Anaesth. 2002 Mar;49(3):249-55
11861342
Nat Med. 1996 Nov;2(11):1248-50
8898754
J Pain. 2009 May;10(5):447-85
19411059
Eur J Pain. 2004 Oct;8(5):397-411
15324772
Life Sci. 2003 May 2;72(24):2675-88
12679185
Pain. 2003 Dec;106(3):253-261
14659508
Neurosci Biobehav Rev. 2000 Jun;24(4):485-501
10817845
Anesth Analg. 2008 Jul;107(1):83-95
18635471
Anesthesiology. 2000 Aug;93(2):539-47
10910505
J Pain. 2005 Jun;6(6):372-83
15943959
Spine (Phila Pa 1976). 2006 Jun 1;31(13):1496-502
16741461
Neurosci Lett. 1996 Mar 1;205(3):207-9
8852594
J Pain. 2011 Mar;12(3):340-51
21146469
Percept Psychophys. 1980 Jun;27(6):499-504
7393696
J Physiol Anthropol. 2009;28(3):129-36
19483374
Eur J Pain. 2004 Oct;8(5):413-25
15324773
Gynecol Obstet Invest. 2005;59(1):49-53
15467297
J Pain. 2005 Feb;6(2):116-24
15694878
Brain Res. 2002 Mar 1;929(1):1-9
11852025
Am J Physiol Regul Integr Comp Physiol. 2006 Aug;291(2):R245-56
16484434
Anesthesiology. 2004 Jan;100(1):120-33
14695733
Pain. 1979 Jun;6(3):375-382
460938
Pain. 2007 Nov;132 Suppl 1:S3-S12
17951003
Pain. 2005 Aug;116(3):227-237
15964682
Pain. 1999 Nov;83(2):339-45
10534607
Brain Res. 1990 Jan 22;507(2):312-6
2337771
Eur J Pain. 2008 May;12(4):472-9
17869144
Urology. 2007 Oct;70(4):681-4
17991537
Neuroscience. 1995 Nov;69(2):345-9
8552232
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Mar;105(3):308-15
18280964
J Pain. 2008 Apr;9(4):337-41
18201935
J Appl Physiol (1985). 2001 Dec;91(6):2785-801
11717247
J Nippon Med Sch. 2002 Feb;69(1):19-23
11847505
J Pharmacol Exp Ther. 2002 Feb;300(2):695-701
11805235
Psychol Bull. 1992 Jul;112(1):155-9
19565683
Can J Anaesth. 1996 Nov;43(11):1108-14
8922765
J Neurosci. 2006 May 24;26(21):5777-85
16723535