Dose-response and time-response relationships between progesterone and the display of patterns of receptive and proceptive behavior in the female rat

Fadem, Barbara H.; Barfield, Ronald J.; Whalen, Richard E.

doi:10.1016/0018-506x(79)90033-3

Cited by 166 publications

(52 citation statements)

References 15 publications

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“…Thus, reasonable starting doses for estradiol in ovariectomized rats would be in the range of 2 μg estradiol benzoate s.c., with testing beginning 24-48 h later; this dose/test interval has been shown to mimic proestrus-estrus, both behaviorally and in terms of plasma hormone levels [13]. Likewise, 500 μg of s.c. progesterone is a reasonable starting point for progestin replacement, with testing beginning 4-6 h later [58]. Of course, these testing intervals assume a nuclear steroid receptor-mediated (genomic) effect, whereas recent reports indicate that gonadal steroids may modulate pain thresholds at considerably shorter intervals [57].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Studying sex and gender differences in pain and analgesia: A consensus report

Greenspan

Craft

LeResche

et al. 2007

Pain

871

633

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In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?" Keywords Sex differences; Gonadal hormones; Estrogens The case for studying sex and gender differences in pain and analgesiaThe pain field has moved from debating whether sex differences in pain exist to recognizing the importance of these differences. Attention is now directed toward understanding (1) what conditions lead to the expression of sex and gender differences in pain experience and reactivity, (2) what mechanisms underlie these differences, and (3) how these differences can inform clinical management of pain.As noted in a recent review, at least 79% of animal studies published in Pain over the preceding 10 years included male subjects only, with a mere 8% of studies on females only, and another 4% explicitly designed to test for sex differences (the rest did not specify) [142]. Given the substantially greater prevalence of many clinical pain conditions in women vs. men [20,199], and growing evidence for sex differences in sensitivity to experimental pain and to analgesics [21,41,213], we recommend that all pain researchers consider testing their hypotheses in both sexes, or if restricted by practical considerations, only in females. It is invalid to assume that data obtained in male subjects will generalize to females, and the best non-human model of the modal human pain sufferer -a woman -is a female animal. If only males are examined in a given study, it is important that a rationale for exclusion of females be provided and that the potential limitation in generalizability of the findings be addressed in the discussion, particularly when examining a pain phenomenon that occurs with greater prevalence or severity in females. In both preclinical and clinical studies, a comparison of both sexes will further our understanding of individual differences in sensitivity to pain and analgesia, thus improving our ability to treat and prevent pain in all people. General considerationsTwo issues of terminology are important. First, the term "sex" refers to biologically based differences, while the term "gender" refers to socially based phenomena. Although biological sex exerts a major influence on one's gender identity, sex and gender a...

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Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Studying sex and gender differences in pain and analgesia: A consensus report

Greenspan

Craft

LeResche

et al. 2007

Pain

871

633

View full text Add to dashboard Cite

show abstract

“…21 Rats were tested on both the hot plate and warm water tail withdrawal assays (both 50°C) consecutively in that order (tests were approximately 10 seconds apart). To obtain non-drug response latencies (to lick a hind paw or jump off the hot plate, or to withdraw the tail from warm water), each rat was tested on each assay 3 times: first at time 0 (baseline 1) and then again 10 to 15 minutes later (baseline 2);…”

Section: Nociceptive Testingmentioning

confidence: 99%

Gonadal hormone modulation of mu, kappa, and delta opioid antinociception in male and female rats

Stoffel

Ulibarri

Folk

et al. 2005

The Journal of Pain

101

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Previous studies suggest that sex differences in morphine antinociception in rodents might be attributed to the activational effects of gonadal hormones. The present study determined whether hormonal modulation of opioid antinociception in adult rats extends to opioids other than the prototypic mu agonist morphine. Male and female rats were sham-gonadectomized (sham-GDX) or gonadectomized (GDX) and replaced with no hormone, estradiol (E2, females), progesterone (P4, females), E2+P4 (females), or testosterone (males). Approximately 28 days later, nociception was evaluated on the 50°C hot plate and warm water tail withdrawal tests before and after subcutaneous administration of hydromorphone, buprenorphine, U50,488, or SNC 80. In sham-GDX (gonadally intact) rats, the mu agonists and U50,488 were less effective in females than in males in at least one nociceptive test, and the delta agonist SNC 80 was less effective in males than in females. In males, gonadectomy tended to decrease, and testosterone tended to increase antinociception produced by 3 of the 4 agonists. In females, gonadectomy and hormone treatment had more variable effects, although E2 tended to decrease mu opioid antinociception. The present results suggest that activational effects of gonadal hormones are relatively modest and somewhat inconsistent on antinociception produced by various opioid agonists in the adult rat.Perspective: This study demonstrates that reproductive hormones such as testosterone in males and estradiol in females do not consistently modulate sensitivity to the analgesic effects of opioids in the adult organism. KeywordsTestosterone; estradiol; progesterone; pain; analgesia; sex differences Accumulating evidence suggests that there are sex differences in the acute antinociceptive effects of opioids in rodents, with males generally displaying greater opioid sensitivity than females.14 Several variables that might influence the observation of sex differences in opioid antinociception include the efficacy/selectivity of the opioid, the type and intensity of the noxious stimulus, and the genotype of the subject. 5 , 13 , 15 , 29 , 36 , 37 , 49 Sex differences in opioidCorrespondence to: Rebecca M. Craft.Address reprint requests to Rebecca M. Craft, PhD,

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“…Testing began at approximately 1400 hours, to occur within the period of P4's peak reproductive effect, 4-6 h post-injection (e.g. Fadem et al, 1979). To obtain nondrug response latencies (to lick a hindpaw or jump off the plate), each rat was tested on the 50°C and then 54°C hotplates, three times: first at time 0 (baseline 1), then again 15 min later (baseline 2); immediately following this second baseline test, saline was administered (1 ml/ kg, s.c.) and rats were tested a third time on each hotplate 30 min later (saline test).…”

Section: 33mentioning

confidence: 99%

“…T and E2 were given chronically because single-dose acute administration of these steroids will not fully restore reproductive behavior. P4 was given intermittently to approximate the cyclic changes in progestins observed in intact cycling females, and females were tested approximately 4-6 h after P4 injection because that is the peak time of P4's effect on reproductive behavior and physiology (Fadem et al, 1979;Feder, 1981).…”

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

169

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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Dose-response and time-response relationships between progesterone and the display of patterns of receptive and proceptive behavior in the female rat

Cited by 166 publications

References 15 publications

Studying sex and gender differences in pain and analgesia: A consensus report

Studying sex and gender differences in pain and analgesia: A consensus report

Gonadal hormone modulation of mu, kappa, and delta opioid antinociception in male and female rats

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

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