Sex differences in morphine-induced analgesia of visceral pain are supraspinally and peripherally mediated

2006 ◽  
Vol 291 (2) ◽  
pp. R307-R314 ◽  
Author(s):  
Yaping Ji ◽  
Anne Z. Murphy ◽  
Richard J. Traub
Keyword(s):  
Sex Difference ◽  
Visceral Pain ◽  
Somatic Tissue ◽  
Female Rats ◽  
Male Rats ◽  
Opioid Analgesia ◽  
Morphine Analgesia ◽  
Intact Male ◽  
Morphine Dose ◽  
Male And Female Rats

Increasing evidence suggests there is a sex difference in opioid analgesia of pain arising from somatic tissue. However, the existence of a sex difference in visceral pain and opioid analgesia is unclear. This was examined in the colorectal distention (CRD) model of visceral pain in the current study. The visceromotor response (vmr) to noxious CRD was recorded in gonadally intact male and female rats. Subcutaneous injection of morphine dose-dependently decreased the vmr in both groups without affecting colonic compliance. However, morphine was significantly more potent in male rats than females. Because systemic morphine can act at peripheral tissue and in the central nervous system (CNS), the source of the sex difference in morphine analgesia was determined. The peripherally restricted μ-opioid receptor (MOR) antagonist naloxone methiodide dose-dependently attenuated the effects of systemic morphine. Systemic administration of the peripherally restricted MOR agonist loperamide confirmed peripherally mediated morphine analgesia and revealed greater potency in males compared with females. Spinal administration of morphine dose-dependently attenuated the vmr, but there was no sex difference. Intracerebroventricular administration of morphine also dose-dependently attenuated the vmr with significantly greater potency in male rats. The present study documents a sex difference in morphine analgesia of visceral pain that is both peripherally and supraspinally mediated.

SEX DIFFERENCES IN THE CONCENTRATIONS OF GLUCOCORTICOID RECEPTORS IN RAT LIVER AND THYMUS

1979 ◽  
Vol 80 (1) ◽  
pp. 21-26 ◽  
Author(s):  
D. B. ENDRES ◽  
R. J. MILHOLLAND ◽  
F. ROSEN
Keyword(s):  
Sex Differences ◽  
Sex Difference ◽  
Glucocorticoid Receptors ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Intact Male ◽  
Male And Female ◽  
Male And Female Rats

The effects in rats of adrenalectomy, hypophysectomy, ovariectomy or combinations of these operations on the concentrations of glucocorticoid receptors in the cytosol of liver and thymus were measured. The concentrations of glucocorticoid receptors were lower in cytosols from liver and thymus of female than of male rats. After adrenalectomy, there was a significant increase in the concentrations of receptors measured in the cytoplasm from the liver and thymus of female rats and from the liver of male rats. After adrenalectomy or hypophysectomy, there was no sex difference in the concentrations of glucocorticoid receptors in cytosols of liver or thymus. After ovariectomy, the concentration of receptors in cytosols from the thymus, but not from the liver, increased. Ovariectomized rats responded to adrenalectomy in the same way as intact male rats. The different responses shown by male and female rats to endocrine manipulation probably depend upon associated changes in plasma corticosterone concentrations which are influenced by the ovary. Differences in response between the liver and thymus probably reflect a preferential distribution of corticosterone to the liver rather than to the thymus.

Sex Differences in Cholinergic Analgesia I 

1999 ◽  
Vol 91 (5) ◽  
pp. 1447-1447 ◽  
Author(s):  
Astrid Chiari ◽  
Joseph R. Tobin ◽  
Hui-Lin Pan ◽  
David D. Hood ◽  
James C. Eisenach
Keyword(s):  
Sex Difference ◽  
Intrathecal Administration ◽  
Female Rats ◽  
Male Rats ◽  
Muscarinic Agonist ◽  
Noxious Heat ◽  
Male And Female Rats ◽  
Adrenergic Antagonist ◽  
Cholinergic Agents ◽  
Dose Dependent

Background Cholinergic agents produce analgesia after systemic and intrathecal administration. A retrospective review showed that intrathecal neostigmine was more potent in women than in men, suggesting a sex difference in this response. The purpose of this study was to determine whether such a sex difference exists in normal rats and to examine the pharmacologic mechanisms that underlie this difference. Methods Male and female rats with indwelling intrathecal catheters received injections of neostigmine, bethanechol (muscarinic agonist), or RJR-2403 (neuronal nicotinic agonist) alone or with atropine (muscarinic antagonist), mecamylamine (nicotinic antagonist), or phentolamine alpha-adrenergic antagonist) with antinociception determined to a noxious heat stimulus to the hind paw. Time versus subcutaneous paw temperature relationships were defined for males and females. Results Neostigmine produced dose-dependent antinociception with five times greater potency in female than in male rats. Neostigmine-induced antinociception was reversed in male rats by atropine and unaffected by mecamylamine, whereas it was partially reduced by each antagonist alone in females and completely reversed after injection of both. RJR-2403 was more potent in females than in males, whereas there was no sex difference to bethanechol. Phentolamine partially reversed antinociception from RJR-2403 in females. Paw temperature increased more rapidly in females than in males for the same lamp intensity. Conclusions These data demonstrate a large sex difference in antinociception to intrathecal neostigmine that is primarily the result of a nicotinic component in females. Phentolamine reversal suggests that part of this nicotinic component may rely on spinal norepinephrine release. A better understanding of this sex difference could lead to development of novel pain therapy for women.

Effect of the anterior pituitary gland and gonads on enzyme components of the hepatic microsomal cytochrome P-450 system of male and female rats

1983 ◽  
Vol 96 (2) ◽  
pp. 259-267 ◽  
Author(s):  
B. Gillham ◽  
J. S. M. Hutchinson ◽  
M. B. Thorn
Keyword(s):  
Sex Difference ◽  
Anterior Pituitary ◽  
Testosterone Propionate ◽  
Specific Activity ◽  
Female Rats ◽  
Intact Male ◽  
Adult Rats ◽  
Microsomal Cytochrome ◽  
Male And Female Rats ◽  
Cytochrome P 450

The concentration of cytochrome P-450 in microsomes prepared from the livers of mature female Wistar-derived rats was significantly lower than in mature males. This sex difference was abolished after hypophysectomy, when the concentration of the cytochrome in males and females was not significantly different from that in the intact male. A concentration of cytochrome P-450 characteristic of females was restored by two anterior pituitary transplants under the kidney capsule of hypophysectomized females; a partial 'feminization' occurred in similarly treated hypophysectomized males. A partial 'feminization' was also achieved by the administration of rat or sheep prolactin to hypophysectomized females. Unexpectedly, the administration of l-dihydroxyphenylalanine to normal females was without effect on cytochrome P-450, whereas in intact males 'feminization' resulted. Castration of adult rats resulted in the 'feminization' of cytochrome P-450, whereas ovariectomy was without effect. Administration of testosterone propionate for 10 days, either immediately after the operation or 14 weeks later to rats castrated when adult failed, however, to reverse the fall in cytochrome P-450. The establishment of a higher concentration of cytochrome P-450 in the liver of female rats could not be brought about by the administration of testosterone propionate, whether given as a single dose on the second day after birth or as a 10-day course of treatment after puberty or both. It is concluded that the sex difference in hepatic microsomal cytochrome P-450 is maintained by the release in the female of an anterior pituitary factor(s) that serves to depress its concentration. The factor(s) shows some of the characteristics of prolactin but the findings are not consistent with that hormone being responsible for all of the effects observed. The release of the factor(s) in the male may be inhibited by a compound of gonadal origin other than testosterone. A sex difference could not be 'imprinted' in the female by either neonatal and/or postpubertal testosterone treatment. The concentration of hepatic microsomal cytochrome b5 and the specific activity of NADPH-cytochrome c reductase were found not to be sex-dependent in the rats used. However, anterior pituitary factor(s) other than prolactin and growth hormone act to suppress partially the concentration of the former and to promote the specific activity of the latter in the endoplasmic reticulum of rat hepatocytes.

Sex Differences in Cholinergic Analgesia II 

1999 ◽  
Vol 91 (5) ◽  
pp. 1455-1455 ◽  
Author(s):  
Patricia M. Lavand'homme ◽  
James C. Eisenach
Keyword(s):  
Nerve Injury ◽  
Sex Difference ◽  
Female Rats ◽  
Male Rats ◽  
Saline Control ◽  
Muscarinic Agonist ◽  
Intraplantar Injection ◽  
Male And Female Rats ◽  
Adrenergic Antagonist ◽  
Cholinergic Agents

Background Cholinergic agents reduce allodynia after nerve injury in animals and may be useful in the treatment of neuropathic pain. Intrathecally administered neostigmine and neuronal nicotinic agonists are more potent in female than in male rats against acute thermal noxious stimuli. The purpose of this study was to determine whether there is also a sex difference in the antiallodynic effects of intrathecal cholinomimetic agents in two models of allodynia and to test their pharmacologic mechanisms. Methods Male and female rats with indwelling intrathecal catheters received injections of neostigmine, bethanechol (muscarinic agonist), RJR-2403 (neuronal nicotinic agonist) alone or with atropine (muscarinic antagonist), mecamylamine (nicotinic antagonist), phentolamine (alpha-adrenergic antagonist), or saline control. The effect of these agents was determined on mechanical allodynia produced by either intraplantar injection of capsaicin or ligation of spinal nerves. Results Neostigmine and RJR-2403 but not bethanechol were more potent in female than in male rats in reducing allodynia after nerve injury, and antagonist studies were also consistent with a nicotinic component to explain this sex difference. Phentolamine did not reverse neostigmine's effect. In contrast, for capsaicin-induced allodynia, neostigmine plus mecamylamine but not neostigmine or RJR-2403 was more potent in female than in male rats. Conclusions These data demonstrate a sex difference of intrathecal neostigmine after nerve injury-induced allodynia similar to that observed in normal animals that received acute noxious thermal stimulation. However, this sex difference is not universal to all pain models because it was not present after intradermal capsaicin injection, nor is its interaction with spinal noradrenergic mechanisms consistent in all models.

INVOLVEMENT OF INHIBIN IN THE REGULATION OF FOLLICLE-STIMULATING HORMONE CONCENTRATIONS IN PREPUBERTAL AND ADULT, MALE AND FEMALE RATS

1980 ◽  
Vol 86 (1) ◽  
pp. 79-92 ◽  
Author(s):  
W. P. HERMANS ◽  
E. C. M. VAN LEEUWEN ◽  
M. H. M. DEBETS ◽  
F. H. DE JONG
Keyword(s):  
Follicle Stimulating Hormone ◽  
Female Rats ◽  
Male Rats ◽  
Intact Male ◽  
Adult Rats ◽  
Physiological Factor ◽  
Male And Female ◽  
Male And Female Rats ◽  
Pituitary Secretion ◽  
Fast Acting

Administration of steroid-free bovine follicular fluid (bFF), containing inhibin-like activity, depressed levels of FSH measured 4 h after injection in intact adult and 35-day-old female rats, but not in younger females. Suppression of FSH was also observed in intact male rats, aged 55 days, but not in older and younger male rats. Eight hours after injection of bFF, FSH levels were depressed in 15-day-old and older immature and adult rats of both sexes. Male and female rats, gonadectomized 2 days earlier, responded similarly to bFF treatment as did the intact animals. In a second experiment it was found that the rise of FSH levels, occurring within 8 h of gonadectomy, decreased with age in male and increased with age in female rats. Steroid treatment was found to prevent the rise in FSH levels partially in 15-day-old male and completely in 25-day-old female rats, whereas treatment with bFF was fully effective in blocking the FSH rise in both immature and adult rats of both sexes. It is concluded that inhibin might be a major physiological factor in a fast-acting control of FSH concentrations from at least the age of 25 days onwards in female rats. In male rats its physiological significance might be limited to the prepubertal period, despite the fact that pituitary secretion of FSH is suppressed by exogenous inhibin-like activity at all ages studied.

Incidence, growth and oestradiol-receptor levels of 7,12-dimethylbenz(a)anthracene-induced mammary tumours in rats: effects of neonatal sex steroids and oestradiol implants

1982 ◽  
Vol 95 (3) ◽  
pp. 357-368 ◽  
Author(s):  
G. Verhoeven ◽  
G. Vandoren ◽  
W. Heyns ◽  
E. R. Kühn ◽  
J. P. Janssens ◽  
...  
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Intact Female ◽  
Intact Male ◽  
Tumour Incidence ◽  
Tumour Induction ◽  
Male And Female Rats ◽  
Neonatal Administration ◽  
Low Levels ◽  
Intact Rats

The effects of neonatally administered steroids on the sensitivity of the mammary gland to tumour induction by 7,12-dimethylbenz(a)anthracene was studied as a model for delayed (de)differentiating effects of steroid hormones. Immediately after birth male and female rats were gonadectomized and treated with testosterone, oestradiol or oil. Control animals were left intact. On day 45 all the gonadectomized animals and some of the control animals received an implant which delivered continuous low levels of oestradiol. The carcinogen was administered on day 55. The administration of an oestradiol implant, which increased prolactin levels in all animals, markedly reduced tumour incidence in intact female rats and increased tumour incidence in intact male rats. Neonatal administration of testosterone or oestradiol did not significantly influence tumour incidence, histopathology or oestradiol responsiveness in neonatally gonadectomized rats but tended to decrease tumour oestradiol-receptor levels. This lack of effect of neonatal steroids in gonadectomized animals suggests that the effects observed by other authors in intact rats are mediated by changes in gonadal secretions. It is concluded that the hormonal environment during and after tumour induction plays a major role in the development of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas.

EFFECTS OF TESTOSTERONE ON PITUITARY CORTICOTROPHIN AND ADRENAL STEROID SECRETION IN MALE AND FEMALE RATS

1963 ◽  
Vol 43 (4) ◽  
pp. 601-608 ◽  
Author(s):  
Julian I. Kitay
Keyword(s):  
Plasma Corticosterone ◽  
Female Rats ◽  
Male Rats ◽  
Intact Male ◽  
Male And Female ◽  
Adrenal Steroid ◽  
Adrenal Steroidogenesis ◽  
Male And Female Rats

ABSTRACT Administration of a depot testosterone preparation to male and female rats resulted in no change in body or pituitary weight in either sex. Pituitary corticotrophin content was unaltered in male animals but was reduced in females. Adrenal weights and adrenal RNA and DNA contents were decreased in both sexes. Plasma corticosterone concentrations were unaffected in males but were reduced in female rats after stress or corticotrophin injection. Hepatic reduction of ring A in vitro and biological half-life of corticosterone in vivo were unchanged in male animals but impaired in females. Testosterone administration to intact male rats significantly increased adrenal steroidogenesis measured in vitro. A significant decrease in steroid production was found in intact females but increased steroidogenesis was observed in adrenals from testosterone-treated oophorectomized animals. No effect was obtained following addition of testosterone directly in vitro. The data suggest that testosterone leads both to diminution of corticotrophin secretion and enhancement of adrenal steroid secretory capacity. In intact female rats, these effects are complicated by suppression of oestrogen secretion, the effects of which have been reported previously.

Sex difference in growth hormone feedback in the rat

1990 ◽  
Vol 126 (1) ◽  
pp. 27-35 ◽  
Author(s):  
L. M. S. Carlsson ◽  
R. G. Clark ◽  
I. C. A. F. Robinson
Keyword(s):  
Growth Hormone ◽  
Sex Difference ◽  
Female Rats ◽  
Male Rats ◽  
Constant Infusion ◽  
Physiological Control ◽  
Sampling System ◽  
Male And Female ◽  
Gh Secretion ◽  
Male And Female Rats

ABSTRACT Growth hormone inhibits its own secretion in animals and man but the mechanism for this inhibition is unclear: both stimulation of somatostatin release and inhibition of GH-releasing factor (GRF) release have been implicated. We have now studied the GRF responsiveness of conscious male and female rats under conditions of GH feedback induced by constant infusion of exogenous human GH (hGH). Intravenous infusions of hGH (60 μg/h) were maintained for 3 to 6 h whilst serial injections of GRF(1–29)NH2 (0·2–1 μg) were given at 45-min intervals. The GH responses were studied by assaying blood samples withdrawn at frequent intervals using an automatic blood sampling system. We have confirmed that male and female rats differ in their ability to respond to a series of GRF injections; female rats produced consistent GH responses for up to 13 consecutive GRF injections, whereas male rats showed a 3-hourly pattern of intermittent responsiveness. In female rats, multiple injections of GRF continued to elicit uniform GH responses during hGH infusions, whereas hGH infusions in male rats disturbed their intermittent pattern of responsiveness to GRF, and their regular 3-hourly cycle of refractoriness was prolonged. We suggest that this sex difference in GH feedback may be due to GH altering the pattern of endogenous somatostatin release differentially in male and female rats. Such a mechanism of GH autofeedback could be involved in the physiological control of the sexually differentiated pattern of GH secretion in the rat. Journal of Endocrinology (1990) 126, 27–35

Estrogen and prothrombin synthesis: effect of estrogen on absorption of vitamin K1

1977 ◽  
Vol 232 (1) ◽  
pp. H12-H17 ◽  
Author(s):  
D. W. Jolly ◽  
C. Craig ◽  
T. E. Nelson
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Thoracic Duct Lymph ◽  
Albino Rats ◽  
Vitamin K1 ◽  
Intact Male ◽  
Deficient Diet ◽  
Castrate Male ◽  
Male And Female ◽  
Male And Female Rats

Intact male and female albino rats fed a vitamin K-deficient diet develop a plasma prothrombin-proconvertin deficiency. Male rats respond with a precipitous drop to approximately 20–30% of normal plasma levels within 2–5 days, whereas female rats respond at a slower rate. Ethynylestradiol, 5–10 mug/day, or castration, reduces the progressive decline of plasma prothrombin-proconvertin seen in nonsupplemented intact male rats. The response of castrate females differs little from the response of intact females. Ethynylestradiol, 5–10 mug/day, affects both castrate males and females similarly, limiting the prothrombin-proconvertin decrease to about 13% below control value after 14 days. Intestinal absorption of vitamin K1 measured in the thoracic duct lymph of pentobarbital-anesthetized castrate male and female rats was shown to increase significantly after estrogen treatment. Estrogen-treated castrate male and female rats absorbed 25.8 mug and 11.8 mug vitamin K1, respectively. Nontreated control castrate male and female rats absorbed 0.0 mug and 1.2 mug, respectively, during a 240-min collection period. Use of radioactive vitamin K1 in similar experiments confirmed these results. Estrogen-treated castrate males absorbed vitamin K1 at the rate of 30-40 mug/g lymph whereas nontreated control males absorbed only about 6 mug/g lymph.

PUBERTAL MANIFESTATION OF SEX DIFFERENCE IN CIRCADIAN RHYTHM OF CORTICOTROPHIN-RELEASING ACTIVITY IN THE RAT HYPOTHALAMUS

1977 ◽  
Vol 86 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Sato Honma ◽  
Tsutomu Hiroshige
Keyword(s):  
Circadian Rhythm ◽  
Sex Difference ◽  
Developmental Change ◽  
Marked Change ◽  
Female Rats ◽  
Male Rats ◽  
Ovarian Activity ◽  
Essential Difference ◽  
Male And Female ◽  
Male And Female Rats

ABSTRACT Post-natal development of the circadian rhythm of hypothalamic content of corticotrophin-releasing factor (CRF) was examined in male and female rats, separately. CRF activity was estimated by the intrapituitary injection technique. The circadian rhythm of the CRF content observed at the third week was without any noticeable sex difference: both male and female rats began their circadian rhythm with higher values in the afternoon than in the morning. Male rats maintained this pattern up to maturity. In contrast, female rats showed a marked change at ages of fifth to sixth week: the CRF rhythm in female rats changed to a female pattern, with higher values in the morning than in the afternoon. During this period, the vaginal opening occurred concurrently with a marked afternoon rise in the plasma corticosterone, characteristic of mature female rats. On the other hand, no essential difference could be observed between male and female rats in the developmental change in the circadian rhythm of locomotor activity. These results indicate that a sex difference in the CRF rhythm is not essentially related to the process of sex differentiation in the central nervous system, but is rather related to changes in ovarian activity following the onset of puberty.

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