Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen has been implicated in modulation of pain processing. Although this modulation occurs within the CNS, estrogen may also act on primary afferent neurons whose cell bodies are located within the dorsal root ganglia (DRG). Primary cultures of rat DRG neurons were loaded with Fura-2 and tested for ATP-induced changes in intracellular calcium concentration ([Ca(2+)](i)) by fluorescent ratio imaging. ATP, an algesic agent, induces [Ca(2+)](i) changes via activation of purinergic 2X (P2X) type receptors and voltage-gated Ca(2+) channels (VGCC). ATP (10 microM) caused increased [Ca(2+)](i) transients (226.6+/-16.7 nM, n = 42) in 53% of small to medium DRG neurons. A 5-min incubation with 17 beta-estradiol (100 nM) inhibited ATP-induced [Ca(2+)](i) (164+/-14.6 nM, P<0.05) in 85% of the ATP-responsive DRG neurons, whereas the inactive isomer 17 alpha-estradiol had no effect. Both the mixed agonist/antagonist tamoxifen (1 microM) and specific estrogen receptor antagonist ICI 182780 (1 microM) blocked the estradiol inhibition of ATP-induced [Ca(2+)](i) transients. Estradiol coupled to bovine serum albumin, which does not diffuse through the plasma membrane, blocked ATP-induced [Ca(2+)](i), suggesting that estradiol acts at a membrane-associated estrogen receptor. Attenuation of [Ca(2+)](i) transients was mediated by estrogen action on VGCC. Nifedipine (10 microM), an L-type VGCC antagonist mimicked the effect of estrogen and when co-administered did not increase the estradiol inhibition of ATP-induced [Ca(2+)](i) transients. N- and P-type VGCC antagonists omega-conotoxin GVIA (1 microM) and omega-agatoxin IVA (100 nM), attenuated the ATP-induced [Ca(2+)](i) transients. Co-administration of these blockers with estrogen induced a further decrease of the ATP-induced [Ca(2+)](i) flux. Together, these results suggest that although ATP stimulation of P2X receptors activates L-, N-, and P-type VGCC, estradiol primarily blocks L-type VGCC. The estradiol regulation of this ATP-induced [Ca(2+)](i) transients suggests a mechanism through which estradiol may modulate nociceptive signaling in the peripheral nervous system.
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PMID:Estradiol inhibits atp-induced intracellular calcium concentration increase in dorsal root ganglia neurons. 1273 39

Many gastrointestinal pain syndromes are more prevalent in women than men, suggesting a gonadal steroid influence. We characterized the effects of estrogen on two responses to colorectal distention (CRD) in the rat: the visceromotor reflex (vmr) and L6-S1 dorsal horn neuron activity (ABRUPT and SUSTAINED neurons). Ovariectomized rats were injected with estrogen, and responses to innocuous and noxious intensities of CRD were measured between 4 hr and 14 d after injection and compared with ovariectomized and intact, cycling rats. Plasma estrogen levels were determined at each time point. Ovariectomy significantly decreased the magnitude of the vmr and ABRUPT neuron response to CRD compared with cycling rats. Four and 48 hr after estrogen injection (10 microg), the magnitude of the vmr and ABRUPT neuron response returned to the level or greater than that of cycling rats. All responses were comparable with ovariectomized rats by 7 d. These results paralleled the plasma estrogen concentration. Fifty micrograms of estrogen did not further increase the magnitude of the vmr or neuronal response 48 hr after estrogen but did extend the period of the increased ABRUPT neuron response to 14 d. Estrogen did not affect the response of SUSTAINED neurons. In a separate experiment, the response to innocuous CRD was sensitized in estrogen-treated rats but not ovariectomized or cycling rats. The present data suggest that estrogen modulates the spinal cord processing and reflex responses to innocuous and noxious colorectal stimuli in female rats and may contribute to alterations in sensory processing associated with irritable bowel syndrome.
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PMID:Estrogen modulates the visceromotor reflex and responses of spinal dorsal horn neurons to colorectal stimulation in the rat. 1273 60

Cyclooxygenase inhibitors demonstrate effective antinociception in many clinical and experimental pain models. Acute uterine cervical distension (UCD) forms the basis for obstetric and some gynecologic pain, and acute UCD in rats results in nocifensor reflexes which are inhibited by morphine in animals lacking, but not in animals with circulating estrogen. We studied the antinociceptive effect of intravenous and intrathecal injection of the cyclooxygenase inhibitor, ketorolac in acute UCD rats and its dependency on estrogen. Virgin rats received estrogen or placebo treatment for 1 week following oviarectomy. An intrathecal catheter was inserted for drug administration. Rats were anesthetized, then the electromyographic response in the rectus abdominus muscle and mean arterial blood pressure change to UCD was recorded before and with cumulative dosing of intravenous or intrathecal ketorolac. Intravenous ketorolac produced dose dependent inhibition of the responses to UCD, but intrathecal ketorolac was ineffective at the maximum test dose (300 microg). Estrogen replacement did not affect the stimulus response or maximum efficacy of ketorolac. Unlike morphine, which reduces response to UCD by spinal and supraspinal mechanisms and whose action is blocked by estrogen, the cyclooxygenase inhibitor, ketorolac acts at an estrogen-independent, non spinal site.
Pain 2003 Sep
PMID:Systemic, but not intrathecal ketorolac is antinociceptive to uterine cervical distension in rats. 1449 26

Estrogen exerts a strong influence on episodic headaches, such as migraine and tension-type headache. A relationship between sex hormones and chronic daily headache (CDH) is less well established. However, similarities between episodic and CDH suggest that estrogen also may significantly influence CDH. Pathophysiologic studies of CDH identify neurochemical abnormalities similar to those influenced by estrogen in episodic headache, such as aberrant 5-hydroxytryptamine activity. In addition, gender differences in CDH prevalence in pediatric and adult populations support a hormonal influence. Few studies have evaluated the ability of gynecologic events, such as menses, to influence CDH.
Curr Pain Headache Rep 2004 Feb
PMID:Estrogen and chronic daily headache. 1473 85

Sexual dysfunction is defined as "disturbances in sexual desire and in the psychophysiological changes that characterize the sexual response cycle and cause marked distress and interpersonal difficulty". The female sexual response cycle consists of three phases: desire, arousal, and orgasm. Various organs of the external and internal genitalia, e.g. vagina, clitoris, labia minora, vestibular bulbs, pelvic floor muscles and uterus, contribute to female sexual function. During sexual arousal, genital blood flow and sensation are increased. The vaginal canal is moistened (lubrication). During orgasm, there is rhythmical contraction of the uterus and pelvic floor muscles. Within the central nervous system, hypothalamic, limbic-hippocampal structures play a central role for sexual arousal. Sexual arousal largely depends on the sympathetic nervous system. Moreover, nonadrenergic/noncholinergic neurotransmitters (NANC), e.g. vasoactive intestinal polypeptide (VIP) and nitric oxide (NO), are involved in smooth muscle relaxation and enhancement of genital blood flow. Furthermore, various hormones may influence female sexual function. Estrogen has a significant role in maintaining vaginal mucosal epithelium as well as sensory thresholds and genital blood flow. Androgens primarily affect sexual desire, arousal, orgasm and the overall sense of well-being. The internationally accepted classification of female sexual dysfunction consists of hypoactive sexual desire disorders, sexual aversion disorders, sexual arousal disorders, orgasmic disorders and sexual pain disorders. Vascular insufficiency, e.g. due to atherosclerosis, and neurologic diseases, e.g. diabetic neuropathy, are major causes of sexual dysfunction. Additionally, sexual dysfunction may be due to changes in hormonal levels, medications with sexual side effects or of psychological origin. For the diagnosis of female sexual dysfunction, a detailed history should be taken initially, followed by a physical examination and laboratory studies. Physiologic monitoring of parameters of arousal potentially allows to diagnose organic diseases. Recordings at baseline and following sexual stimulation are recommended to determine pathologic changes that occur with arousal. Duplex Doppler sonography, photoplethysmography or the measurement of vaginal and minor labial oxygen tension may help to evaluate genital blood flow. Moreover, measurements of vaginal pH and compliance should be performed. Neurophysiological examination, e.g. measurement of the bulbocavernosus reflex and pudendal evoked potentials, genital sympathetic skin response (SSR), warm, cold and vibratory perception thresholds as well as testing of the pressure and touch sensitivity of the external genitalia, should be performed to evaluate neurogenic etiologies. Medical management of female sexual dysfunction so far is primarily based on hormone replacement therapy. Application of estrogen results in decreased pain and burning during intercourse. The efficacy of various other medications, e.g. sildenafil, L-arginine, yohimbine, phentolamine, apomorphine and prostaglandin E1, in the treatment of female sexual dysfunction is still under investigation.
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PMID:[Female sexual dysfunction: a systematic overview of classification, pathophysiology, diagnosis and treatment]. 1588 Sep 11

Estrogen (E2) and/or progesterone (P) in the amygdala may influence anxiety, fear, and pain behaviors. Ovariectomized rats were administered subcutaneous or intra-amygdala vehicle, E2, P, or E2 + P: Effects on open field, elevated plus-maze, defensive freezing, and hot-plate task performance were observed. Subcutaneous E2 + P or intra-amygdala E2, P, or E2 + P increased open field central entries and open arm time in the plus-maze compared with vehicle. Subcutaneous or intra-amygdala E2, P, or E2 + P decreased time spent freezing postshock compared with vehicle. Subcutaneous or intra-amygdala E2 + P increased latencies to lick paws compared with vehicle. Thus, E2 and P may have effects in the amygdala to decrease anxiety, fear, and/or pain responses.
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PMID:Estrogen and/or progesterone administered systemically or to the amygdala can have anxiety-, fear-, and pain-reducing effects in ovariectomized rats. 1511 56

(1) The reference hormone-based contraceptive for women is an oral contraceptive combining ethinylestradiol (about 30 micrograms) and a well-known progestin such as levonorgestrel or norethisterone. (2) A transdermal contraceptive patch delivering 20 micrograms of ethinylestradiol and 150 micrograms of norelgestromin over 24 hours, and designed to be left in place for a whole week, three weeks a month, has recently been marketed in France. (3) Norelgestromin is the active metabolite of norgestimate, which is already available in combined contraceptives but is less well evaluated than some other progestins. Norelgestromin is metabolised by the liver, notably into norgestrel. (4) The clinical evaluation dossier of the new transdermal contraceptive contains data from two comparative unblinded trials, one versus a triphasic combination of oral ethinylestradiol + levonorgestrel, and the other versus oral ethinyl estradiol (20 micrograms) + desogestrel. A third, non comparative trial offers weaker evidence. These three trials included about 3300 women in total, and lasted between 6 and 13 cycles. The patch was about as effective as the comparator contraceptives. (5) In the three main clinical trials, 4.7% of patches had to be replaced because they became unstuck, either completely (1.8%) or partially (2.9%). (6) More women dropped out of the groups using patches (19.9% of the patch group compared with 14.5% of the group taking oral contraceptives in one trial, 29.6% versus 24.3% in the other trial). Women using the patch were more likely than other women to stop their treatment because of adverse events (about 12% versus 5%). (7) Breast discomfort, breast tenderness or pain were reported by 22% of women using the patches and by 9% and 6% of women in the two comparator groups. Women using the patches had slightly longer menstrual periods (5.6 days versus 4.7 days). Reactions at the patch site were reported by 17% of women. (8) There is no evidence that the patch is any less likely than reference oral contraceptives to cause thromboembolism. The true thromboembolic risk associated with the new patches is unknown. (9) Used patches still contain large amounts of active substances, and must be placed in sachets (provided in the packet) and taken to a pharmacy for disposal. (10) In practice, the reference combined contraceptive for women is still oral ethinylestradiol (about 30 micrograms) plus a well-known progestin such as levonorgestrel or norethisterone. Ethinylestradiol + norelgestromin patches offer women no real benefits: they are probably less convenient and may be less safe.
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PMID:Ethinylestradiol + norelgestromin: new preparation. Transdermal contraception: no tangible progress. 1553 34

Sex differences in pain have been confirmed both in clinical and experimental studies. Estrogen has a great role in this process and can affect response to noxious stimuli. In this study, we used Fos as a marker to investigate the mechanism underlying the phenomenon. Sprague-Dawley rats were randomly assigned to ovariotomy (OVX) or sham surgery (OVX-sham) group (n=20 rats/condition). All the rats received CCI surgery three weeks after ovariotomy. We used hot-plate test as a sign of neuropathic pain. On PO days 3, 7, 14, and 21, paw withdrawal latency was determined and 2 h later, the L4-L5 segments of the spinal cord were removed and immunostained for Fos protein. Number of Fos-like immunoreactive (Fos-LI) neurons of each section was counted bilaterally. We find that ovariotomy can regulate the sensitivity to thermal stimuli and Fos protein level will change in the spinal dorsal horn. However, the alternation of Fos expression does not extremely account for the behavior.
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PMID:Ovariotomy and persistent pain affect long-term Fos expression in spinal cord. 1569 53

Estrogen increases reflex nocifensive responses to distension of the uterus and the urinary bladder, but estrogen's effects on afferent response to distension of the uterine cervix, the site of obstetric and some gynecologic pain, has not been studied. Here, single fiber recording of hypogastric nerve responses to uterine cervical distension were obtained from ovariectomized (OVX) rats and OVX rats treated with estrogen (ES). Spontaneous activity was greater in the ES group (13 of 24 units; 54%) than in the OVX group (6 of 27 units; 22%). ES differentially altered the response of low- and high-threshold units to distension. For high-threshold units, firing frequency was increased two- to fourfold with 60-100 gm distension in ES compared with OVX groups (P < 0.05). In contrast, the response of low-threshold units to distension was not altered by ES. About one-half of units tested in each group responded to a temperature increase from 35 to 49 degrees C. A greater proportion of thermosensitive units were also mechanosensitive in the ES group (7 of 8 afferents, 88%) than in the OVX group (5 of 11 afferents, 45%). Acute application of ES in OVX rats failed to evoke or increase distension-induced responses. These data show the polymodal nature of afferent fibers innervating the uterine cervix. Increased spontaneous activity with ES may play a part in remodeling of the cervical tissue, whereas selective sensitization of high-threshold units by ES might underlie increased pain responses to cervical distension. Failure of acute ES treatment to mimic this suggests a genomic effect.
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PMID:Chronic estrogen sensitizes a subset of mechanosensitive afferents innervating the uterine cervix. 1577 14

The paper provides a generalization of data and the results of own experiments on influence ovarian steroids on the hypothalamus and other brain areas related to reproduction. Ovarian hormones have widespread effects throughout the brain: on catecholaminergic neurons and serotonergic pathways and the basal forebrain cholinergic system, as well as the hipocampus, spinal cord, nigrostriatal and mesolimbic system, in addition to glial cells and blood-brain barrier. The widespread influences of these various neuronal systems ovarian steroids have measurable effects on mood and affect as well as on cognition, with implications for dementia. There are developmentally programmed sex differenced in hippocampal structure that may help to explain differences in the strategies which male and female rats use to solve spatial navigation problems. The multiple sites and mechanisms of estrogen action in brain underlie a variety of importants effects on cognitive and other brain functions--coordination of movement, pain, affective state, as well as possible protection in Alzheimer's disease. Estrogen withdrawal after natural or surgical menopause can lead to a host of changes in brain function and behavior.
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PMID:[Neuroendocrine effect of sex hormones]. 1581 Jun 81


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