Skip to main content
SpringerLink
Log in

Opioid-induced analgesia and respiratory depression: Sex differences

  • Chapter
Physiology And Pharmacology of Cardio-Respiratory Control

Abstract

Exogenous Opioids such as morphine exert powerful physiological effects, including analgesia and respiratory depression. These effects exhibit marked inter-individual differences, however. In addition to the well-documented effects of age/development and genetic background, the contribution of sex and hormonal status as a factor in Opioid potency is becoming increasingly appreciated. Progress in this area has been slow, perhaps since most studies on the analgesic and respiratory effects of Opioids utilize male subjects to avoid the need to control for estrous/menstrual status. Additionally, sex differences in opioid analgesia have been reported by some to be either negligible or absent. This may reflect differences in the methodology-species, strain and age of the animals, particular nociceptive assay employed and its parameters-employed by each laboratory. Nonetheless, findings from an increasing number of studies directly examining the issue of sex and hormonal status in the potency of Opioids demonstrate that sex and hormonal factors need to be considered if opioid drugs are to be used in the most efficacious manner possible.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ali B, Sharif S, Elkadi A: Sex differences and the effect of gonadectomy on morphine-induced antinociception and dependence in rats and mice. Clin Exp Pharmacol Physiol 1995; 22:342–344

    Article  PubMed  CAS  Google Scholar 

  2. Baamonde AI, Hidalgo A, Adrés-Trelles F: Sex-related differences in the effects of morphine and stress on visceral pain. Neuropharmacol 1989; 28: 967–970

    Article  CAS  Google Scholar 

  3. Banarjee P, Chatterjee TK, Ghosh JJ: Ovarian steroids and modulation of morphine-induced analgesia and catalepsy in female rats. Eur J Pharmacol 1983; 96: 291–294

    Article  Google Scholar 

  4. Bartok RE, Craft RM: Sex differences in Opioid antinociception. J Pharmacol Exp Ther 1997; 282: 769–778

    PubMed  CAS  Google Scholar 

  5. Berglund LA, Simpkins JW: Alterations in brain opiate receptor mechanisms on proestrous afternoon. Neuroendocrin 1988; 48: 394–400

    Article  CAS  Google Scholar 

  6. Berkely KJ: Sex differences in pain. Behav Brain Sci 1997; 20: 371–380

    Google Scholar 

  7. Bodnar RJ, Romeo M-T, Kramer E: Organismic variables and pain inhibition: roles of gender and aging. Brain Res Bull 1988; 21: 947–953

    Article  PubMed  CAS  Google Scholar 

  8. Bond MR, Pilowsky I: Subjective assessment of pain and its relationship to the administration of analgesics in patients with advanced cancer. J Psychosom Res 1966; 10: 203–208

    Article  PubMed  CAS  Google Scholar 

  9. Boyle P, Parbrook GD: The interrelation of personality on post-operative factors. BrJ Anaesth 1977;49:259–264

    Article  CAS  Google Scholar 

  10. Burns JW, Hodsman NBA, McLIntock TTC, Gillies GWA, Kenny GNC, McArdle CS: The influence of patient characteristic on the requirements for postoperative analgesia. Anaes 1989; 44: 2–6

    Article  CAS  Google Scholar 

  11. Candido J, Lufty K, Billings B, Sierra V, Duttaroy A, Inturrisi CE, Yoburn BC: Effect of adrenal and sex hormones on opioid analgesia and opioid receptor regulation. Pharmacol Biochem Behav 1992; 42: 685–692

    Article  PubMed  CAS  Google Scholar 

  12. Chatterjee TK, Das S, Banarjee P, Ghosh JJ: Possible physiological role of adrenal and gonadal steroids in morphine analgesia. Eur J Pharmacol 1982; 77: 119–123

    Article  PubMed  CAS  Google Scholar 

  13. Cicero TJ, Newman KS, Meyer ER: testosterone does not influence opiate binding sites in the male rat brain. Life Sci 1983; 33: 1231–1239

    Article  PubMed  CAS  Google Scholar 

  14. Cicero TJ, Nock B, Meyer ER: Gender-related differences in the antinociceptive properties of morphine. J Pharmacol Exp Ther 1996; 279: 763–773

    Google Scholar 

  15. Cleeland CS, Gonin R, Hatfield AK, Edmonson JH, Blum RH, Stewart JA, Pandya KJ: Pain and its treatment in outpatients with metastatic cancer. New Eng J Med 1998; 330: 592–596

    Article  Google Scholar 

  16. Dawson KH, Egbert MA, Myall RW: Pain following iliac crest bone grafting of alveolar clefts. J Pharmacol Exp Ther 1996; 24: 151–154

    CAS  Google Scholar 

  17. Dason-Basoa M, Gintzler AR: Estrogen and progesterone activate spnial kappa-opiate receptor analgesic mechanisms. Pain 1996; 64: 169–177

    Article  Google Scholar 

  18. Diez JA, Roberts JL: Evidence contradicting the notion that gonadal hormones regulate brain opiate receptors. Biochem Biophys Res Comm 1982; 108: 1313–1319

    Article  PubMed  CAS  Google Scholar 

  19. Fields HL, Heinricher MM, Mason P: Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci 1991; 14: 219–245

    Article  PubMed  CAS  Google Scholar 

  20. Gear RW, Miakowski C, Gordon NC, Paul SM, Heller PH, Levine JD: Kappa-opioids produce significantly greater analgesia in women than in men. Nature Med 1995; 11: 1248–1250

    Google Scholar 

  21. Gordon NC, Gear RW, Heller PH, Paul S, Miakowski C, Levine JD. Enhancement of morphine analgesia by GABAB agonist baclofen. Neurosci 1995; 69: 345–349

    Article  CAS  Google Scholar 

  22. Hahn EF, Fishman J: Castration affects male rat brain opiate receptor content. Neuroendocrin 1985;41:60–63

    Article  CAS  Google Scholar 

  23. Islam AK, Cooper ML, Bodnar RJ: Interactions among aging, gender and gonadectomy affects upon morphine antinociception in rats. Physiol Behav 1993; 54: 43–54

    Google Scholar 

  24. Jacquet YF: The NMDA receptor: central role in pain inhibition in rat periaqueductal gray. Eut J Pharmacol 1988; 154: 271–276

    Article  CAS  Google Scholar 

  25. Kaiko RF, Wallenstein SL, Rogers AG, Houde RW: Sources of variation in analgesic responses in cancer patients with chronic pain receiving morphine. Pain 1983; 15: 191–200

    Article  PubMed  CAS  Google Scholar 

  26. Kasson BG, George R: Endocrine influences on the actions of morphine. IV. Effects of sex and strain. Life Sci 1984; 34: 1627–1634

    Article  PubMed  CAS  Google Scholar 

  27. Kavaliers M, Innes DGL: Sex and day-night differences in opiate-induced responses of insular wild deer mice, peromyscus maniculatus triangularis. Pharmacol Biochem Behav 1987; 27: 477–482.

    Article  PubMed  CAS  Google Scholar 

  28. Kavaliers M, Innes DGL: Sex differences in the effects of Tyr-MIF-1 on morphine-and stress-induced analgesia. Peptides 1992; 13: 1295–1297

    Article  PubMed  CAS  Google Scholar 

  29. Kavaliers M, Innes DGL: Sex differences in the effects of neuropeptide FF and IgG from neuropeptide FF on morphine-and stress-induced analgesia. Peptides 1992; 13: 603–607

    Article  PubMed  CAS  Google Scholar 

  30. Kavaliers M, Innes DGL: Sex differences in the antinociceptive effects of the enkephalinase inhibitor SCH 34826. Pharmacol Biochem Behav 1993; 46: 777–780

    Article  PubMed  CAS  Google Scholar 

  31. Kepler KL, Kest B, Kiefel JM, Cooper ML, Bodnar RJ: Roles of gender, gonadectomy and estrous phase in the analgesic effects of intracerebroventricular morphine in rats. Pharmacol Biochem Behav 1989; 34: 119–127

    Article  PubMed  CAS  Google Scholar 

  32. Kepler KL, Standifer KM, Paul D, Kest B, Pasternak GW, Bodnar RJ: Gender effects and central opioid analgesia. Pain 1991; 45: 87–94

    Article  PubMed  CAS  Google Scholar 

  33. Kest B, Brodsky M, Sadowski B, Mogil JS, Inturrisi CE: Mu opioid receptor (MOR-1) mRNA levels are altered in mice with differential analgesic sensitivity to the mu opioid DAMGO. Analgesia 1995; 1:498–501

    CAS  Google Scholar 

  34. Kest B, Wilson SG, Mogil JS: Genetic mediation of supraspinal morphine analgesia: strain and sex differences. 1998; in preparation

    Google Scholar 

  35. Lipa SM. Kavaliers M: Sex differences in the inhibitory effects of the NMDA antagonist MK-801 on morphine and stress-induced analgesia. Brain Res Bull 1990; 24: 627–630

    Article  PubMed  CAS  Google Scholar 

  36. McQuay HJ, Bullingham RES, Paterson GMC, Moore RA: Clinical effects of buprenorphine during and after operation. Br J Anaesth 1980; 52: 1013–1019

    Article  PubMed  CAS  Google Scholar 

  37. Mogil JS, Marek P, O’Toole LA, Helms ML, Sadowski B, Liebeskind JC, Belknap JK: Muopiate receptor binding is upregulated in mice selectively bred for high stress-induced analgesia. Brain Res 1994; 853: 16–22

    Article  Google Scholar 

  38. Mogil JS, Richards SP, O’Toole LA, Helms ML, Mitchell SR, Kest B, Belknap JK: Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice. J Neurosci 1997; 20: 7995–8002

    Google Scholar 

  39. Moskowitz AS, Terman GW, Carter KR, Morgan MJ, Liebeskind JC: Analgesic, locomotor and lethal effects of morphine in the mouse: strain comparisons. Brain Res 1985; 361: 46–51

    Article  PubMed  CAS  Google Scholar 

  40. Parsons CG, Czlonkowski A, Stein C, Herz A: Peripheral opioid receptors mediating antinociception in inflammation: activation by endogenous Opioids and the role of the pituitary-adrenal axis. Pain 1990; 41: 81–93

    Article  PubMed  CAS  Google Scholar 

  41. Petersen SL, La Flamme KD: Progesterone increases levels of μ-opioid receptor mRNA in the preoptic area and arcuate nucleus of ovariectomized, estradiol-treated female rats. Mol Brain Res 1997;52:32–37

    Article  PubMed  CAS  Google Scholar 

  42. Ratka A, Simpkins JW: Effects of estradiol and progesterone on the sensitivity to pain on morphine-induced antinociception in female rats. Horm Behav 1991; 25: 217–228

    Article  PubMed  CAS  Google Scholar 

  43. Schul R, Frenk H: The role of serotonin in analgesia elicited by morphine in the periaqueductal gray matter (PAG). Brain Res 1991; 553: 353–357

    Article  PubMed  CAS  Google Scholar 

  44. Simerly RB, Swanson L, Gorski RA: Demonstration of a sexual dimorphism in the distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus of the rat. J Comp Neurol 1984; 225: 151–166

    Article  PubMed  CAS  Google Scholar 

  45. Simerly RB, McCall LD, Watson SJ: Distribution of opioid peptides in the pre-optic region: immunohistochemical evidence for a steroid-sensitive enkephalin sexual dimorphism. J Comp Neurol 1988; 276: 442–459

    Article  PubMed  CAS  Google Scholar 

  46. Twycross RG: Choice of strong analgesic in terminal cancer: diamorphine or morphine? Pain 1977; 3:93–104

    Article  PubMed  CAS  Google Scholar 

  47. Vaught JL, Takemori AE: Differential effects of leucine and methionine enkephalin on morphine-induced analgesia, acute tolerance and dependence. J Pharmacol Exp Ther 1979; 208: 86–90

    PubMed  CAS  Google Scholar 

  48. Watson RE, Hoffmann GE, Wiegand SJ: Sexually dimorphic Opioid distribution in the preoptic area: manipulation by gonadal steroids. Brain Res 1986; 398: 157–163

    Article  PubMed  CAS  Google Scholar 

  49. Weiland NG, Wise PM: Estrogen and progesterone regulate opiate receptor densities in multiple brain regions. Endocrin 1990; 126: 804–808

    Article  CAS  Google Scholar 

  50. Wilkinson M, Brawer JR, Wilkinson DA: Gonadal steroid-induced modification of opiate binding sites in anterior hypothalamus of female rats. Biol Reprod 1985; 32: 501–506

    Article  PubMed  CAS  Google Scholar 

  51. Graff KJ, Kennedy RM, Jaffe DM: Conscious sedation for pediatric orthopedic emergencies. Ped Emer Care 1996; 12: 31–35

    Article  CAS  Google Scholar 

  52. Dahan A, Sarton E, Teppema L, Olievier C: Sex-related differences in the influence of morphine on ventilatory control in humans. Anesthesiology 1998; 88: 903–913

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Benjamin Kest
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elise Sarton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeffrey S. Mogil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Albert Dahan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Leiden University Medical Center, Leiden, The Netherlands

    Albert Dahan  & Luc Teppema  & 

  2. Free University, Amsterdam, The Netherlands

    Johannes H. G. M. van Beek

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Kest, B., Sarton, E., Mogil, J.S., Dahan, A. (1998). Opioid-induced analgesia and respiratory depression: Sex differences. In: Dahan, A., Teppema, L., van Beek, J.H.G.M. (eds) Physiology And Pharmacology of Cardio-Respiratory Control. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5129-0_14

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-5129-0_14

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6156-8

  • Online ISBN: 978-94-011-5129-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation