Sex differences and phases of the estrous cycle alter the response of spinal cord dynorphin neurons to peripheral inflammation and hyperalgesia

Bradshaw, Heather B.; Miller, Julie E.; Ling, Qing-Dong; Malsnee, K.; Ruda, M.A.

doi:10.1016/s0304-3959(99)00253-5

Cited by 82 publications

(59 citation statements)

References 23 publications

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“…The result is compatible with previously reported epidemiologic studies in human populations (6,8,38) and laboratory experiments in animals (1,3,7,17,34,35) showing that the female is highly sensitive to noxious stimuli and pain. On the other hand, our present results suggest the possibility that the male urethra is affected more evidently.…”

Section: Ajp-regul Integr Comp Physiolsupporting

confidence: 92%

Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice

Yoshiyama¹,

Kobayashi²,

Araki³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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related differences in lower urinary tract (LUT) activity responding to intravesical infusion of diluted acetic acid (A/A, pH 3.0) were investigated during cystometrograms in decerebrate unanesthetized mice. A/A produced a decrease of intercontraction intervals in both female and male animals, and the extent of the decrease in male mice was much less than in female mice [19 Ϯ 5% (P ϭ 0.03) vs. 65 Ϯ 5% (P ϭ 0.03); n ϭ 6 for each], exhibiting a marked difference between the two groups in response to acid irritation of the LUT (P ϭ 0.002). A/A reduced maximal voiding pressure (MVP) (19 Ϯ 4%, P ϭ 0.03) but had no effect on pressure threshold for inducing voiding contraction (PT) (P ϭ 0.56) in females, whereas A/A did not change MVP (P ϭ 1.00) but increased PT (16 Ϯ 4%, P ϭ 0.03) in males. A/A decreased bladder compliances of female and male mice in a similar fashion (44 Ϯ 10% vs. 24 Ϯ 7%, P ϭ 0.03 for each). In male mice, A/A produced persistent dribbling of fluid after voiding contraction phase, which was virtually not seen in females. The present study demonstrates the differences between female and male mice in response to noxious stimulation in the LUT: the female bladder is more sensitive to the acid irritation, while the male urethra is more irritable to the noxious stimulus. Identification of mechanisms underlying sex-specific characteristics might be helpful for elucidating pathogenesis of painful bladder syndrome. afferent; bladder tonus; detrusor contractility; efferent; urethral resistance NUMEROUS IN VIVO PHYSIOLOGICAL and pharmacological studies examining bladder and urethral activity have been conducted exclusively in one sex of animals in each experimental design, and thus it is uncertain whether functional responses of female and male lower urinary tracts are similar. There are only a few articles detailing differences between females and males in the lower urinary tract functions. Of the available reports, for example, one previous study comparing female and male rats in cystometry revealed that volume thresholds for inducing micturition were changed in accordance with altered intravesical infusion rates in the female rat, whereas these were constant regardless of the bladder filling rates in the male (24). The study suggested the possibility that mechanosensory afferent responses to intensity of the mechanical stimulus were different between the female and male animals.Epidemiologic studies have demonstrated sex-specific differences in prevalence and incidence of certain diseases. In the urological field, it has been well documented that prevalence and incidence of interstitial cystitis, which is a syndrome consisting of severe refractory bladder symptoms such as suprapubic pain, urinary frequency, and urgency without a specific identifiable cause, for women are significantly higher than those for men (10). What pathophysiological factors are involved in these sex-related differences?Here, we proposed the possibilities that sex differences in mechanisms responsible for transmitting inflammatory pai...

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Section: Ajp-regul Integr Comp Physiolsupporting

confidence: 92%

Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice

Yoshiyama¹,

Kobayashi²,

Araki³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Thresholds were lower in nonarthritic rats during proestrus and in arthritic rats thresholds were lower during estrus and proestrus. Although a definitive conclusion regarding the influence of circulating hormones cannot be made, these results complement those demonstrating greater thermal hyperalgesia in arthritic rats during the proestrus phase (Bradshaw et al, 2000).…”

Section: Discussionsupporting

confidence: 66%

Nociceptive Sensitivity and Opioid Antinociception and Antihyperalgesia in Freund's Adjuvant-Induced Arthritic Male and Female Rats

Cook

Nickerson²

2004

J Pharmacol Exp Ther

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The present study was designed to examine sex differences in complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia and sex differences in opioid antinociception and antihyperalgesia. Female rats developed inflammation and hyperalgesia faster and exhibited greater peak hyperalgesia than male rats. In arthritic (CFA-treated) rats, lower thresholds were observed during estrus and proestrus, and in nonarthritic (vehicle-treated) rats, lower thresholds were observed during proestrus. Morphine and oxycodone were more potent in male than female arthritic rats, and butorphanol was more potent and effective in male than female arthritic rats. The potency of morphine was increased in arthritic rats, although to a greater magnitude in males. The potency of oxycodone was increased in male but not female arthritic rats. The potency of butorphanol was increased in arthritic male rats and the maximal antinociceptive effect of butorphanol was increased in arthritic female rats, but it did not result in greater than 20% antinociception. Morphine, oxycodone, and butorphanol all produced antihyperalgesic effects (returning thresholds of arthritic rats to the thresholds of nonarthritic rats) with greater potency in males than females. The peripherally acting opioid agonist loperamide produced intermediate levels of antinociception in male and female arthritic rats and no antinociception in nonarthritic rats. Loperamide was more potent in male than female arthritic rats at producing antihyperalgesia. These data demonstrate sex differences in arthritis-induced hyperalgesia and responsiveness to opioid analgesics. In arthritic rats, the antinociceptive effects of opioid agonists are most probably mediated by both central and peripheral opioid receptors, whereas their antihyperalgesic effects are mediated primarily by actions at peripheral opioid receptors.

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“…Evidence has shown that estrogen affected chronic inflammation [9,10]. We then investigated the effect of estrogen on OVX CFA rats.…”

Section: Estrogen Replacement Reversed the Decrease Of Pwt In Ovariecmentioning

confidence: 99%

“…Mechanical hyperalgesia and allodynia in the abdomen, hind limbs, and proximal tail of OVX rats, which result from a lack of estrogen in the body, can be reversed by sustaining exogenous estradiol replacement [8]. During several days or weeks after inflammation or injury, estrogen promotes the development of heat hyperalgesia and mechanical hyperalgesia [9,10]. The estrogen effects depend on the type, time course of pain or inflammation models, and also the level and stability of estrogens [7].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

Jiang

Sun

et al. 2016

Purinergic Signalling

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Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041. In 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, weight loss, higher DAI scores, increased visceromotor responses, and inflammatory responses were reversed by application of DPN or ERB-041. The higher expressions of P2X3R in dorsal root ganglia (DRG) of CFA-treated rats and those in rectocolon and DRG of TNBS-treated rats were all decreased by injection of DPN or ERB-041. DPN application also inhibited P2X3R-evoked inward currents in DRG neurons from TNBS rats. Mechanical hyperalgesia and increased P2X3 expression in ovariectomized (OVX) CFA-treated rats were reversed by estrogen replacements. Furthermore, the expressions of extracellular signal-regulated kinase (ERK) in DRG and spinal cord dorsal horn (SCDH) and c-fos in SCDH were significantly decreased after estrogen replacement compared with those of OVX rats. The ERK antagonist U0126 significantly reversed mechanical hyperalgesia in the OVX rats. These results suggest that estrogen may play an important therapeutic role in inflammation through downregulation of P2X3R in peripheral tissues and the nervous system, probably via ERβ, suggesting a novel therapeutic strategy for clinical treatment of inflammation.

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Sex differences and phases of the estrous cycle alter the response of spinal cord dynorphin neurons to peripheral inflammation and hyperalgesia

Cited by 82 publications

References 23 publications

Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice

Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice

Nociceptive Sensitivity and Opioid Antinociception and Antihyperalgesia in Freund's Adjuvant-Induced Arthritic Male and Female Rats

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

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