Sex-related differences in the antinociceptive effects of opioids: importance of rat genotype, nociceptive stimulus intensity, and efficacy at the µ opioid receptor

Cook, Charles D.; Barrett, Andrew C.; Roach, Emily L.; Bowman, Joseph R.; Picker, Mitchell J.

doi:10.1007/s002130000453

Cited by 158 publications

(157 citation statements)

References 24 publications

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“…Previous studies have shown that the intensity of the noxious stimulus used in the pain test can influence the magnitude of sex differences in opioid antinociception (Negus and Mello, 1999;Cook et al, 2000;Craft and Bernal, 2001;Barrett et al, 2002), and in nociceptive thresholds (e.g. Aloisi et al, 1995).…”

Section: Effect Of Nociceptive Stimulus Intensitymentioning

confidence: 99%

“…Sex differences in opioid antinociception also are widely reported in rodents, although they tend to be in the opposite direction to those observed in humans. For example, morphine was significantly more potent or produced a greater effect in male than in female mice (Kavaliers and Innes, 1987;Lipa and Kavaliers, 1990;Candido et al, 1992) and rats (Baamonde et al, 1989;Cicero et al, 1996;Craft et al, 1999;Cook et al, 2000). Variables that may influence the magnitude of sex differences in opioid antinociception in rodents include opioid efficacy/selectivity, intensity of the noxious stimulus used in the pain test, and subject genotype (i.e.…”

Section: Introductionmentioning

confidence: 99%

“…Variables that may influence the magnitude of sex differences in opioid antinociception in rodents include opioid efficacy/selectivity, intensity of the noxious stimulus used in the pain test, and subject genotype (i.e. rodent strain) (Kest et al, 1999;Mogil et al, 2000;Cook et al, 2000;Craft and Bernal, 2001;Barrett et al, 2002). Sex differences in opioid analgesia have also been reported in the rhesus monkey Mello, 1999, 2002); these sex differences are similar to those observed in rodent studies, using similar tests of acute thermal nociception.…”

Section: Introductionmentioning

confidence: 99%

“…Intensity of the noxious stimulus is another procedural variable that differs among studies of gonadal steroid modulation of nociception. Group differences in basal nociception and opioid antinociception have been shown to vary in size (and significance) with the intensity of the noxious stimulus used in the nociceptive test (Morgan et al, 1999;Negus and Mello, 1999;Cook et al, 2000;Craft and Bernal, 2001;Barrett et al, 2002;Terner et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats

Stoffel

Ulibarri

Craft

2003

Pain

168

137

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The purpose of this study was to examine how gonadal steroid hormones modulate basal nociception and morphine antinociception relative to regulating reproduction in the adult rat. Male and female Sprague-Dawley rats were either gonadectomized (GDX) or sham-gonadectomized (sham); GDX males were implanted subcutaneously with capsules containing testosterone (T), estradiol (E2), dihydrotestosterone (DHT), E2 and DHT, or nothing (0). GDX females received E2, T, or empty (0) capsules immediately after surgery, and vehicle or progesterone (P4) injections at 4-day intervals. Basal nociception and morphine antinociception were tested 28 days after surgery on 50°C and 54°C hotplate tests, and reproductive behavior and physiology were assessed shortly thereafter. There were no significant differences in baseline hotplate latencies among the male treatment groups, but morphine was significantly more potent in sham and GDX + T males than in GDX + 0 males. The ability of T to increase morphine's potency was approximated by its major metabolites E2 and DHT, given together but not alone. Baseline hotplate latencies were higher in sham females tested during diestrus than in those tested during estrus. Morphine was significantly more potent in sham females tested during proestrus and diestrus than in those tested during estrus. Baseline hotplate latencies were significantly higher, and morphine was significantly less potent in GDX + E2, GDX + E2/P4 and GDX + T females than in GDX + 0 females. All group differences in basal nociception and morphine antinociception observed on the 50°C hotplate test were smaller and generally nonsignificant on the 54°C hotplate test. Steroid manipulations produced the expected changes in reproductive behaviors and steroid-sensitive organs. These results demonstrate that in adult rats, gonadal steroid manipulations that are physiologically relevant, modulate (1) basal nociception in females but not males, and (2) morphine's antinociceptive potency in both males and females.

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Section: Effect Of Nociceptive Stimulus Intensitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats

Stoffel

Ulibarri

Craft

2003

Pain

168

137

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“…After a one-week wash out period, similar experiments were performed with fentanyl. It was reported that repeated use of opioids did not lead to tolerance if the exposure was separated by 5-7 days (Cook et al, 2000, Walker et al, 1999. The rats in the control groups remained as controls in the cross over.…”

Section: Hot Plate Testingmentioning

confidence: 99%

Oxidative damage and sensitivity to nociceptive stimulus and opioids in aging rats

Raut

Ratka

2009

Neurobiology of Aging

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Oxidative stress contributes to aging and may cause alterations in pain and analgesia. Knowledge about effects of oxidative stress on the opioid system is very limited. This project was designed to determine the relationship between age-related oxidative damage and opioid antinocicpetion. Three age groups of male Fischer 344 rats were tested for pain sensitivity and responses to morphine and fentanyl using the hot plate method. Oxidative stress markers in various brain regions were measured. With advancing age, nociceptive threshold and antinociceptive effects of opioids decreased significantly. There was a significant negative correlation between morphine antinociception and protein oxidation in cortex, striatum, and midbrain (r 2 = 0.73, 0.87, and 0.77, respectively), and lipid peroxidation in cerebral cortex, hippocampus, and striatum (r 2 = 0.73, 0.61 and 0.71, respectively). Similar correlation was observed between oxidative stress markers and fentanyl antinociception. These findings demonstrate that the age-related increase in oxidative damage in brain is associated with a significant decrease in the antinociceptive effects of opioids.

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Genetic Contributions to Pain and Analgesia

Fillingim

Mogil

2013

Pain Genetics

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Sex-related differences in the antinociceptive effects of opioids: importance of rat genotype, nociceptive stimulus intensity, and efficacy at the µ opioid receptor

Cited by 158 publications

References 24 publications

Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats

Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats

Oxidative damage and sensitivity to nociceptive stimulus and opioids in aging rats

Genetic Contributions to Pain and Analgesia

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