Gender effects and central opioid analgesia

Kepler, Karen L.; Standifer, Kelly M.; Paúl, Dennis; Kest, Benjamin; Pasternak, Gavril W.; Bodnar, Richard J.

doi:10.1016/0304-3959(91)90168-w

Cited by 168 publications

(79 citation statements)

References 35 publications

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“…The persistence of sex differences in antinociception when opioids are administered i.c.v. [28,29], directly into the RVM [6], or directly into the PAG [31,53] also argues against a purely pharmacokinetic explanation. Thus, sex differences in opioid antinociception are probably caused by one or more pharmacodynamic factors, such as sexually dimorphic brain loci at which opioids act.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, mu opioid receptor expression in vPAG is two-fold higher in male than in female rats [55]. Sex differences in antinociception have been observed after opioid administration to the vPAG [31,53,55] and RVM [6]; however, whereas several studies have shown that supraspinal administration of morphine or DAMGO produces greater antinociception in males [6,28,29,31], other studies have reported greater antinociception in females [53] or no sex difference [27,29]. Disagreement among such studies may result from differences in the type/intensity of the nociceptive stimulus, efficacy of the mu agonist, use of awake vs. anesthetized animals, estrous phase of females, and genotype (strain/vendor) of the rodent [11,12,38].…”

Section: Introductionmentioning

confidence: 99%

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PAG mu opioid receptor activation underlies sex differences in morphine antinociception

Bernal

Morgan

Craft

2007

Behavioural Brain Research

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Given the findings that (1) systemic opioid antinociception varies by estrous stage in females, and (2) the magnitude of sex differences in opioid antinociception is negatively correlated with opioid agonist efficacy, we hypothesized that sex differences in the function of the descending pain modulatory system are likely influenced by estrous stage in females and by the number of available opioid receptors therein. The present study tested these hypotheses by (1) comparing antinociception produced by morphine microinjection to the ventral periaqueductal gray (vPAG) in females at different stages of the estrous cycle, and (2) examining systemic morphine antinociception in males vs. females under conditions of reduced vPAG mu opioid receptor availability. When estrous stage of females was not controlled for (Experiment 1), there was no significant sex difference in tail withdrawal antinociception following morphine microinjection (0.3-10 μg), although morphine was more potent in males than females in producing immobility. Experiment 2 showed that intra-vPAG morphine produced less antinociception and immobility in estrus than in diestrus females; that is, only estrus females' response to morphine was lower than that of males. Experiment 3 showed that microinjection of the irreversible mu opioid antagonist β-funaltrexamine (β-FNA) into the vPAG shifted the systemic morphine dose-effect curve farther to the right in females than in males. That is, a reduction in available vPAG mu opioid receptors had a greater impact on opioid antinociception in females than in males, suggesting that females have fewer vPAG mu opioid receptors than males. Overall, these data suggest that ovarian hormones and PAG mu opioid receptor density contribute to sex differences in antinociception produced by morphine.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PAG mu opioid receptor activation underlies sex differences in morphine antinociception

Bernal

Morgan

Craft

2007

Behavioural Brain Research

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“…For example, gonadectomy of adult male rats or mice has been shown to increase (Chatterjee et al, 1982;Ali et al, 1995), decrease (Rao and Saifi, 1985;, or not affect (Kepler et al, 1989(Kepler et al, , 1991Candido et al, 1992;Islam et al, 1993;Cicero et al, 1996Cicero et al, , 2002Krzanowska and Bodnar, 1999) opioid antinociception. Gonadectomy in adult female rats also has been shown to increase (Kepler et al, 1989;Ali et al, 1995;Krzanowska and Bodnar, 1999;Terner et al, 2002), decrease (Banerjee et al, 1983), or not affect (Kepler et al, 1991;Cicero et al, 1996Cicero et al, , 2002Terner et al, 2002) opioid antinociception. The effect of adult gonadectomy on opioid antinociception has been shown to depend on subject age and opioid dose (Islam et al, 1993), as well as rodent genotype and opioid efficacy .…”

Section: Introductionmentioning

confidence: 99%

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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“…Age and sex-related variations in noradrenergic pain modulation pathways may account for these differences. 41 This observation may provide a new insight into the physiological mechanisms underlying the sex variation in pain perception. 42 The occurrence of morphine side effects was not increased by clonidine as reported here and detailed by others.…”

Section: Discussionmentioning

confidence: 83%

Intraoperative clonidine enhances postoperative morphine patient-controlled analgesia

Kock¹,

Pichon²,

Scholtès³

1992

Can J Anaesth

101

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In this prospective study, the postoperative analgesic effects of intraoperative iv clonidine were evaluated. Two hundred consecutive patients undergoing major abdominal surgery were randomly assigned to either balanced anaesthesia with iv clonidine (Group 1) 55,4 +--30,6 mg versus 67,1 +_ 45,1 mg dans le groupe 2 (P < 0,05); cette diffgrence est plus marquee dans les 12 premiOres heures aprks la chirurgie (19,7 --+ 11,1 mg versus 27,6 +--18,1 mg;P < 0,001 Adequate postoperative analgesia has become a priority. Besides providing patient comfort, it reduces the incidence of complications and the length of hospitalization.I Despite the progress of technology, the exclusive management of pain by epidural or parenteral opiates cannot be achieved without close surveillance or complications. 2 Kehlet recently introduced the concept of postoperative "balanced analgesia" using, among other drugs, opiates, CAN J ANAESTH 1992 / 39:6 / pp 537-44

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Gender effects and central opioid analgesia

Cited by 168 publications

References 35 publications

PAG mu opioid receptor activation underlies sex differences in morphine antinociception

PAG mu opioid receptor activation underlies sex differences in morphine antinociception

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

Intraoperative clonidine enhances postoperative morphine patient-controlled analgesia

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