Sex Differences in Opioid-Induced Analgesia
Research over the past 25 years, including some emanating from our laboratory, has substantively demonstrated that sex differences in analgesic processes occur such that male rodents display greater magnitudes and potencies of morphine and mu-mediated analgesia than female rodents. More recent studies have lent credence to this finding in human volunteers and pain patients. The roles of gonadal hormones through adult and neonatal gonadectomy as well as through exogenous administration of gonadal hormones, have established a strong role for the organizational effects of gonadal hormones in these sex differences. Our laboratory is currently investigating organizational-activational gonadal hormone interactions in subserving sex differences in opioid-induced analgesia as well as the neural circuitry that underlies hormonal fluctuations (e.g., the ventromedial and medial preoptic hypothalamic nuclei) interacting with endogenous pain-inhibitory systems in the periaqueductal gray.
Related Publications of the Bodnar Laboratory:
Cataldo G, J Lovric, C-C Chen, C Pytte and RJ Bodnar. Ventromedial and medial preoptic hypothalamic ibotenic acid lesions potentiate systemic morphine analgesia in female, but not male rats. Behav Brain Res 214: 301-316, 2010.
Bodnar, RJ and B Kest. Sex differences in opioid analgesia, hyperalgesia, tolerance and withdrawal: central mechanisms of action and roles of gonadal hormones. Horm. Behav. 58: 72-81, 2010.
Cataldo, G, K Medina, SY Bernal, S Rozengurtel and RJ Bodnar. Neonatal and adult gonadal hormone manipulations enhance morphine analgesia elicited from the ventrolateral periaqueductal gray in female rats. Int. J. Neurosci 120: 265-272, 2010.
Greenspan, JD, RM Craft, L LeResche, KJ Berkley, RB Fillingim, MS Gold, A Holdcroft, S Lautenbacher, EA Mayer, JS Mogil, AZ Murphy, RJ Traub, AM Aloisi, L Arendt-Neilsen, A Arnold, D Bereiter, J Blaustein, RJ Bodnar, L Chang, A Gintzler, R Hallin, K Hargreaves, E Keogh, P McCarthy, B Naliboff, M Robinson, M Steiner, C Stohler, U Wesselmann, X Xu and E Young. Studying sex and gender differences in pain and analgesia: A consensus report. Pain 132: S26-S45, 2007.
Shane, R, SY Bernal, S Rozengurtel and RJ Bodnar. Estrus phase differences in female rats in morphine antinociception elicited from the ventrolateral periaqueductal gray. Int. J. Neurosci. 117: 811-822, 2007.
Cataldo, G, S Bernal, A Markowitz, S Ogawa, A Ragnauth, DW Pfaff and RJ Bodnar. Organizational manipulation of gonadal hormones and systemic morphine analgesia in female rats: effects of adult ovariectomy and estradiol replacement. Brain Res. 1059: 13-19, 2005.
Krzanowska, EK, S Ogawa, DW Pfaff and RJ Bodnar. Reversal of sex differences in morphine analgesia elicited from the ventrolateral periaqueductal gray in rats by neonatal hormone manipulations. Brain Res. 929: 1-9, 2002.
Bodnar, RJ, K Commons and DW Pfaff. Central neural states relating sex and pain. Johns Hopkins University Press: Baltimore, MD, 258 pp, Published, April, 2002.
Krzanowska, EK, V Znamensky, S Wilk and RJ Bodnar. Antinociceptive and behavioral activation responses elicited by D-Pro2-endomorphin-2 in the ventrolateral periaqueductal gray are sensitive to sex and gonadectomy differences in rats. Peptides 21: 705-715, 2000.
Krzanowska, EK and RJ Bodnar. Analysis of sex and gonadectomy differences in beta-endorphin antinociception elicited from the ventrolateral periaqueductal gray in rats. Eur. J. Pharmacol. 392: 157-161, 2000.
Krzanowska, EK and RJ Bodnar. Sex differences in locomotor activity following beta-endorphin in the ventrolateral periaqueuductal gray. Physiol. Behav. 68: 595-598, 2000.
Krzanowska, EK and RJ Bodnar. Morphine antinociception elicited from the periaqueductal gray is sensitive to sex and gonadectomy differences in rats. Brain Res. 821: 224-230, 1999.
Bodnar, RJ. Pain. In: Behavioral Medicine for Women: A Comprehensive Handbook (Eds., E Blechman and K Brownell) Guilford Publications: New York, Chapter 114, 695-699, 1997.
Islam, AK, ML Cooper and RJ Bodnar. Interactions among aging, gender and gonadectomy effects upon morphine antinociception in rats. Physiol. Behav. 54: 45-53, 1993.
Kiefel, JM and RJ Bodnar. Roles of gender and gonadectomy in pilocarpine and clonidine analgesia in rats. Pharmacol. Biochem. Behav. 41: 153-158, 1992.
Kepler, KL, KM Standifer, D Paul, GW Pasternak, B Kest and RJ Bodnar. Differential gender effects upon central opioid analgesia. Pain 45: 87-95, 1991.
Kepler, KL, B Kest, JM Kiefel, ML Cooper and RJ Bodnar. Roles of gender, gonadectomy and estrous phase in the analgesic effects of intracerebroventricular morphine in rats. Pharmacol. Biochem. Behav. 34: 119-127, 1989.
Romero, M-T, ML Cooper, BR Komisaruk and RJ Bodnar. Gender-specific and gonadectomy-specific effects upon swim analgesia: role of steroid replacement therapy. Physiol. Behav. 44: 257-265, 1988.
Bodnar, RJ, M-T Romero and E Kramer. Organismic variables and pain-inhibition: roles of gender and aging. Brain Res. Bull. 21: 947-953, 1988.
Romero, M-T, KL Kepler and RJ Bodnar. Gender determinants of opioid mediation of swim analgesia in rats. Pharmacol. Biochem. Behav. 29: 705-709, 1988.
Romero, M-T, KL Kepler, ML Cooper, BR Komisaruk and RJ Bodnar. Modulation of gender-specific effects upon swim analgesia in gonadectomized rats. Physiol. Behav. 40: 39-45, 1987.
Romero, M-T and RJ Bodnar. Gender differences in two forms of cold-water swim analgesia. Physiol. Behav. 37: 893-897, 1986.
Badillo-Martinez, D, AL Kirchgessner, PD Butler and RJ Bodnar. Monosodium glutamate and morphine analgesia: test-specific effects. Neuropharmacol. 23: 1141-1149, 1984.