scholarly journals Sex differences in the inflammatory mediator-induced sensitization of dural afferents

2011 ◽  
Vol 106 (4) ◽  
pp. 1662-1668 ◽  
Author(s):  
N. N. Scheff ◽  
M. S. Gold
Keyword(s):  
Sex Difference ◽  
Inflammatory Mediator ◽  
Sodium Current ◽  
Adult Population ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Electrophysiological Properties ◽  
Male And Female Rats ◽  
Dural Afferents

Approximately 20% of the adult population suffers from migraine. This debilitating pain disorder is three times more prevalent in women than in men. To begin to evaluate the underlying mechanisms that may contribute to this sex difference, we tested the hypothesis that there is a sex difference in the inflammatory mediator (IM)-induced sensitization of dural afferents. Acutely dissociated retrogradely labeled dural afferents from adult Sprague-Dawley rats were examined with whole cell patch-clamp recordings. Baseline passive and active electrophysiological properties of dural afferents from both sexes were comparable. However, while IM-induced increases in the excitability of dural afferents from male and female rats were also comparable, the proportion of dural afferents from female rats sensitized by IM (∼100%) was significantly greater than that of dural afferents from male rats (∼50%). This appeared to be due to differences downstream of IM receptors, as tetrodotoxin-resistant sodium current was increased by IM in a majority of male dural afferents (13/14). These data indicate that there are both quantitative and qualitative differences in the IM-induced sensitization of dural afferents that may contribute to the sex difference in the manifestation of migraine.

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.

scholarly journals Intraperitoneal Alfaxalone and Alfaxalone–Dexmedetomidine Anesthesia in Sprague–Dawley Rats (Rattus norvegicus)

2020 ◽  
Vol 59 (5) ◽  
pp. 531-538
Author(s):  
Sylvia E West ◽  
Jonathan C Lee ◽  
Tinika N Johns ◽  
Elizabeth A Nunamaker
Keyword(s):  
Rattus Norvegicus ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Withdrawal Reflex ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Laboratory Rodent ◽  
Physiologic Parameters

Due to their unpredictability and variable effects, injectable anesthetic regimens in laboratory rodent species warrant refinement. In our study we sought to evaluate alfaxalone, which has gained recent popularity in veterinary medicine, alone and in combination with dexmedetomidine to evaluate their anesthetic ability in Sprague–Dawley rats when administered intraperitoneally. Three doses of alfaxalone only and 4 dose combinations of alfaxalone-dexmedetomidine were tested in males and female rats. The time to induction, anesthetic duration, pulse rate, respiratory rate, temperature, and time to recovery were recorded by a blind observer. The level of anesthesia induced by the various anesthetic protocols was assessed by using pedal withdrawal reflex to a noxious stimulus and scored according to the response. Dependent on the treatment group, atipamezole or saline was administered intraperitoneally once animals reached 60 min of anesthesia. Regardless of the dose, alfaxalone alone achieved only a sedative level of anesthesia, whereas all alfaxalone-dexmedetomidine combinations led to a surgical level of anesthesia in all animals. Anesthesia regimens using alfaxalone alone and in combination with dexmedetomidine demonstrated sex-associated differences, with female rats maintaining longer durations of sedation or anesthesia than their male counterparts. Both male and female rats displayed decreases in physiologic parameters consistent with the effects of dexmedetomidine. Given the results described herein, we recommend 20 mg/kg alfaxalone for sedation and 30 mg/kg alfaxalone combined with 0.05 mg/kg dexmedetomidine for surgical anesthesia in female rats. Appropriate doses of alfaxalone only and alfaxalone-dexmedetomidine for male rats were not determined in this study and need further evaluation.

Abstract 386: Compound 21 Induces Natriuresis via Renal AT2 Receptor Activation in Male and Female Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Brandon A Kemp ◽  
Nancy L Howell ◽  
Robert M Carey
Keyword(s):  
Receptor Activation ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Angiotensin Iii ◽  
Compound 21 ◽  
Renal Cortical Interstitium

Endogenous renal des-aspartyl 1 -angiotensin II (angiotensin III) activates renal proximal tubule AT 2 receptors (AT 2 Rs) and induces natriuresis via a nitric oxide-cyclic GMP signaling pathway. The present study explores the ability of highly selective non-peptide AT 2 R agonist Compound 21 (C21) to induce natriuresis. Sprague-Dawley rats (12 weeks old; male N=22; female N=18) were studied in the presence and absence of concurrent 24-h AT 1 R blockade with candesartan (CAND;0.01 mg/kg/min). Rats were anesthetized with Inactin 100 mg/kg i.p., uninephrectomized and instrumented for delivery of 3 cumulative 30-min i.v. infusions of C21 (100, 200, and 300 ng/kg/min) following a 30-min control infusion of vehicle. Mean arterial pressure (MAP) was measured for all periods and urine Na + excretion rate (U Na V) was calculated for the control and final C21 collection periods. To determine whether the systemically induced natriuresis is mediated by renal AT 2 Rs, PD-123319 (PD), a specific AT 2 R antagonist, was infused directly into the renal cortical interstitium(20 μg/kg/min and 10 μg/kg/min for females and males, respectively) during the i.v. C21 infusions. In female rats, C21 increased U Na V from 1.5 ± 0.20 to 7.48 ± 0.95 μmol/min (P<0.0001). This response was abrogated by concurrent intrarenal PD infusion [control 0.74 ± 0.19 vs. C21 2.02 ± 0.50 μmol/min (P<0.001from C21 alone). Systemic CAND administration augmented the natriuretic response to C21 [control 1.29 ± 0.25 vs. C21 10.68 ± 0.70 μmol/min (P<0.05 from C21 alone)]. In male rats, C21 increased U Na V from 0.46 ±0.08 to 6.21 ± 1.33 μmol/min (P<0.01). This response was blocked by concurrent intrarenal PD infusion [control 0.39 ± 0.11 vs. C21 1.69 ± 0.53 μmol/min (P<0.05 from C21 alone). Systemic CAND did not significantly alter the natriuretic response to C21 alone [control 0.49 ± 0.15 vs. C21 7.67 ± 0.72 μmol/min (P = NS from C21 alone). In female rats, CAND augmented the natriuretic response to C21 over that of male rats (P<0.01). Systemic arterial pressures were decreased by CAND in both male and female rats but were unchanged by C21 alone or together with intrarenal PD. C21 induces natriuresis via renal AT 2 R activation in both male and female rats. These data suggest the potential for AT 2 R agonist therapy in hypertension.

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.

Toxic Peripheral Neuropathy with Demyelination in Sprague-Dawley Rats Given CGS 21595 —A 5-Lipoxygenase Inhibitor

1992 ◽  
Vol 29 (2) ◽  
pp. 145-151 ◽  
Author(s):  
D. E. Gunson ◽  
P. S. Sahota ◽  
W. O. Iverson ◽  
R. Y. Chau ◽  
G. M. McCormick ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Recovery Period ◽  
Female Rats ◽  
Male Rats ◽  
Renal Tubules ◽  
Sprague Dawley ◽  
Lipoxygenase Inhibitor ◽  
Male And Female ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

Male and female Sprague-Dawley rats were given CGS 21595, a pro-drug that is almost immediately metabolized to CGS 19213, a naphthoquinone that acts as a 5-lipoxygenase inhibitor. The compound was administered by gavage to five groups of Sprague-Dawley rats (group Nos. 1, 5, n = 30; group Nos. 2–4, n = 20) at daily doses of 0, 50, 150, 500, or 1,000 mg/kg for 13 weeks. Rats in the higher dose groups had a reduced weight gain, but significant neurologic signs were not observed. A peripheral neuropathy consisting predominantly of myelin destruction in the spinal nerve roots and sciatic nerves was seen in male rats treated with ≥ 150 mg/kg CGS 21595 and in female rats treated with ≥50 mg/kg CGS 21595 for 13 weeks. This lesion was not fully reversible after a recovery period of 4 weeks. Lesions consisted of ballooning of myelin sheaths, infiltration by macrophages, demyelination, and occasional areas of remyelination. Axons were generally preserved, and the brain and spinal cord were not affected. Male and female rats in all treatment groups had cytoplasmic hyaline droplets in the proximal renal tubules. This change was reversible after 4 weeks and was not associated with any other adverse effects on the kidney.

scholarly journals Spontaneous Primary Pleural Mesothelioma in Fischer 344 (F344) and Other Rat Strains: A Retrospective Review

2021 ◽  
pp. 019262332110536
Author(s):  
Debra A. Tokarz ◽  
Margarita M. Gruebbel ◽  
Gabrielle A. Willson ◽  
Jerry F. Hardisty ◽  
Gail Pearse ◽  
...  
Keyword(s):  
Retrospective Review ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Rat Strains ◽  
Incidence Data ◽  
Fischer 344 ◽  
Male And Female Rats ◽  
Microscopic Evaluation ◽  
F344 Rats

Spontaneous primary pleural mesotheliomas in Fischer 344 (F344) or other rat strains have rarely been reported. The objectives of this retrospective study were to develop historical incidence data and better characterize the light-microscopic morphology of these naturally occurring neoplasms in a large cohort of rats of several strains. A retrospective review was performed of National Toxicology Program (NTP) studies in rats conducted between 1980 and 2019 and comprising a total of 104,029 rats (51,326 males, 52,703 females), predominantly (90%) of the F344 strain. Of the 94,062 F344 rats surveyed, there were 30 cases of primary pleural mesotheliomas (22 males, 8 females). Of the 2998 Wistar Han rats surveyed, primary pleural mesotheliomas were present in 2 male rats. No primary pleural mesotheliomas were noted in male and female rats of other strains (6669 Sprague Dawley; 300 Osborne-Mendel). All primary pleural mesotheliomas in control and treated F344 and Wistar Han rats were considered spontaneous and unrelated to treatment. Based on light-microscopic evaluation of paraffin-embedded hematoxylin and eosin stained sections, only epithelioid and biphasic histologic subtypes were observed: 18 and 12 in F344 rats, respectively, and one each in Wistar Han rats. No sarcomatoid subtype cases were noted in any strain of rat.

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.

scholarly journals Alcohol and Vapourized Nicotine Co-Exposure During Adolescence Contribute Differentially to Sex-Specific Behavioural Effects in Adulthood

2021 ◽  
Author(s):  
Jessica Ruffolo ◽  
Jude Frie ◽  
Hayley Thorpe ◽  
Malik Talhat ◽  
Jibran Khokhar
Keyword(s):  
Alcohol Drinking ◽  
Preference Test ◽  
Alcohol Preference ◽  
Female Rats ◽  
Fear Learning ◽  
Male Rats ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Male And Female ◽  
Male And Female Rats

Introduction: Co-occurrence of e-cigarette use and alcohol consumption during adolescence is frequent. However, little is known about their long-lasting effects when combined. Here, we examined whether adolescent co-exposure to alcohol drinking and vapourized nicotine would impact reward- and cognition-related behaviours in adult male and female rats during adulthood. Methods: Four groups of male and female Sprague Dawley rats (n=8-11/group/sex) received either nicotine (JUUL 5% nicotine pods) or vehicle vapour daily between postnatal days 30-46, while having continuous voluntary access to ethanol and water during this time in a two-bottle preference design. Upon reaching adulthood, rats underwent behavioural testing utilizing Pavlovian conditioned approach testing, fear conditioning and a two-bottle alcohol preference test. Results: A sex-dependent effect was found in the two-bottle preference test in adulthood such that females had a higher intake and preference for alcohol compared to males regardless of adolescent exposure; both male and female adult rats had greater alcohol preference compared to adolescents. Male rats exposed to vapourized nicotine with or without alcohol drinking during adolescence exhibited altered reward-related learning in adulthood, evidenced by enhanced levels of sign-tracking behaviour. Male rats that drank alcohol with or without nicotine vapour in adolescence showed deficits in associative fear learning and memory as adults. In contrast, these effects were not seen in female rats exposed to alcohol and nicotine vapour during adolescence. Conclusions: The present study provides evidence that co-exposure to alcohol and vapourized nicotine during adolescence in male, but not female, rats produces long-term changes in reward- and cognition-related behaviours.

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

Effects of sex and exercise training on β-adrenoreceptor mediated opposition of evoked sympathetic vasoconstriction in resting and contracting muscle of rats

2020 ◽  
Author(s):  
Ian R. Cooper ◽  
Sixue Liu ◽  
Darren S. DeLorey
Keyword(s):  
Exercise Training ◽  
Triceps Surae ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Contracting Muscle ◽  
Arterial Blood ◽  
Male And Female Rats ◽  
Sympathetic Vasoconstriction ◽  
Main Effect

This study investigated the hypothesis that β-adrenoreceptor mediated inhibition of sympathetic vasoconstriction would be enhanced in female compared to male rats, and that exercise training would augment β-adrenoreceptor inhibition of sympathetic vasoconstriction in male and female rats. Sprague-Dawley rats were randomized into sedentary (Male: n=7; Female: n=8) and exercise trained (Male: n=9; Female: n=9) groups. Following 4 weeks of exercise training or sedentary behavior, rats were anesthetized and surgically instrumented for stimulation of the lumbar sympathetic chain, muscle contraction and measurement of arterial blood pressure and femoral artery blood flow (FBF). Femoral vascular conductance (FVC) was calculated as FBF/mean arterial pressure. The percentage change of FVC in response to sympathetic stimulation delivered at 2 and 5 Hz was measured at rest and during contraction of the triceps surae muscles before and after β-adrenoreceptor blockade (Propranolol;0.075 mg·kg-1, IV). We found that, at rest, β-adrenoreceptor blockade decreased (main effect of drug, 2Hz: P <0.001; 5Hz: P<0.001) sympathetic vasoconstriction. During contraction, sympathetic vasoconstrictor responsiveness was lower (main effect of sex, 2Hz: P=0.001; 5Hz: P=0.023) in female compared to male rats, and sympatholysis was enhanced (main effect of sex, 2 Hz: P=0.001; 5Hz: P<0.001) in female rats. β-adrenoreceptor blockade decreased (main effect of drug, 2Hz: P=0.049; 5Hz: P<0.001) evoked sympathetic vasoconstriction in contracting muscle. The present study demonstrated that β-adrenoreceptors do not blunt sympathetic vasoconstriction in resting or contracting skeletal muscle of male or female rats. Sympatholysis was enhanced in female rats, however, this was not attributable to β-adrenoreceptor mediated blunting of sympathetic vasoconstriction.

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