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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Estrogen and progesterone are known to affect nociception. The plasma concentrations of these hormones vary during estrous cycle in rodents. The aim of the present study was to investigate the effect of evidence of alpha1 receptor agonist and antagonist on tonic pain in all phases of estrous cycle in female rats. Phenylephrine (alpha1 agonist) and prazosin (alpha1 antagonist) were administered via intracerebroventicular (ICV) injection. Adult female rats weighting 200-220 g were maintained on 12 h light/dark cycle for 10-14 days prior to the experiment. Food and water were made available ad libitum. Formalin test was performed in all phases of estrous cycle. Results showed that phenylephrine caused significant (P<0.05) reduction in pain sensitivity. This reduction was more pronounced during proestrus phase. Prazosin significantly (P<0.05) increased pain sensitivity, particularly during metestrus phase. It is possible that fluctuation in pain sensitivity during estrous cycle is related to the level of sex hormones during estrous cycle.
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PMID:CNS alpha 1 receptor in tonic pain during estrous cycle in rats. 1588 62

Estrogen affects many aspects of the nervous system, including pain sensitivity and neural regulation of vascular function. We have shown that estrogen elevation increases sensory nociceptor innervation of arterioles in Sprague-Dawley rat mammary gland, external ear and mesentery, suggesting widespread effects on sensory vasodilatory innervation. However, it is unclear whether estrogen elicits nociceptor hyperinnervation by promoting target release of neurotrophic factors, or by direct effects on sensory neurons. To determine if estrogen may promote axon sprouting by increasing release of target-derived diffusible factors, dorsal root ganglia explants were co-cultured with mesenteric arterioles for 36 h in the absence or presence of 17beta-estradiol (E2). Mesenteric arteriolar target substantially increased neurite outgrowth from explanted ganglia, but estrogen had no effect on outgrowth, suggesting that estrogen does not increase the availability of trophic proteins responsible for target-induced neurite outgrowth. To assess the direct effects of estrogen, dissociated neonatal dorsal root ganglion neurons were cultured for 3 days in the absence or presence of E2 and nerve growth factor (NGF; 1-10 ng/mL), and immunostained for the nociceptor markers peripherin or calcitonin gene-related peptide. NGF increased neuron size, survival and numbers of neurons with neurites, but did not affect neurite area per neuron. Estrogen did not affect neuron survival, size or numbers of neurons with neurites, but did increase neurite area per neuron. The effects of these agents were not synergistic. We conclude that estrogen exerts direct effects on nociceptor neurons to promote axon outgrowth, and this occurs through an NGF-independent mechanism.
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PMID:Estrogen increases sensory nociceptor neuritogenesis in vitro by a direct, nerve growth factor-independent mechanism. 1593 91

Chronic pain induces plastic changes in nociceptive sensory pathways, and is often accompanied and exacerbated by depression. Estrogen can influence nociceptive sensory processing, but the molecular mechanisms underlying sex differences in pain remain unclear. Brain-derived neurotrophic factor (BDNF) may orchestrate changes occurring during persistent pain or depression by increasing spinal nociceptive signaling and altering neuronal growth in higher brain structures. This study addressed whether estrogen regulates BDNF gene expression in central systems associated with nociceptive processing and/or affective state, which may in turn influence sex differences in pain sensitivity. Thus, BDNF gene expression was quantified in intact female rats in proestrus and diestrus, and in ovariectomized (OVX) rats with or without 17beta-estradiol (E2) replacement following intraplantar injection of dilute formalin as an inflammatory nociceptive stimulus. Twenty-four hours after formalin injection, central nervous system (CNS) tissues were removed and solution hybridization-nuclease protection assays used to quantify BDNF mRNA levels. Results demonstrated that estrogen replacement increased BDNF mRNA levels in the hippocampus, cortex and spinal cord. Cortical BDNF mRNA levels were significantly decreased by nociception, in the hippocampus this decrease was only evident in estrogen-treated rats. Spinal BDNF expression was robustly increased by nociception. The pain-evoked up-regulation of spinal BDNF gene expression was significantly potentiated by concomitant estrogen treatment. Results demonstrate that BDNF gene expression in certain brain structures is inhibited by inflammatory pain, yet estrogen may enhance central nervous system sensitization associated with sensory processing. Since alterations in BDNF gene expression in higher brain centers may be relevant to cognitive changes that occur in recurrent depression, these results may provide insights into the coincidence of chronic pain and depression.
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PMID:Estrogen increases nociception-evoked brain-derived neurotrophic factor gene expression in the female rat. 1602 Sep 28

Clinical presentation of temporomandibular joint (TMJ) disorders are more common in women and changes in the female hormone estrogen affect the level of swelling, pro-inflammatory cytokine release and pain in animal models of TMJ arthritis. Estrogen also modulates the expression of the CD16 receptor in vitro. This alters pro-inflammatory cytokine release in monocytes/macrophages when auto-antigens and arthritic factors bind the CD16 receptor. This study investigated the effects of various levels of estrogen on the intensity of inflammation and CD16 expression in a TMJ arthritic animal model. The experiments included rats that were intact or ovariectomized (OVX), eliminating the major source of estrogen output. A portion of the OVX animals had estrogen replaced with 17-beta estradiol (E2) using Alzet pumps. In OVX animals E2 levels were administered for 10 days to create an artificial estrus cycle or to simulate pregnancy. Following E2 treatment the rats were given an intra-articular TMJ injection of saline or complete Freund's adjuvant (CFA). CFA injection significantly increased TMJ swelling, stress induced chromodacryorrhea and attenuated food intake, thus indicating the adjuvant induced TMJ pain/inflammation. Removing endogenous E2 through OVX reduced CFA induced TMJ inflammation, whereas CFA increased the number of TMJ monocytes expressing the CD14 receptor equally in all groups irrespective of plasma E2 levels. Paradoxically, higher levels of E2 reduced the number of TNF-alpha positive, CD16+ and double labeled CD14+/CD16+ cells. The findings indicate that reduced plasma E2 levels attenuated CFA induced TMJ inflammation, whereas increasing E2 levels enhanced TMJ swelling in a dose dependent manner. Estrogenic group differences in CFA induced swelling were independent of TMJ CD14+, CD14+/CD16+ or CD16+ cell numbers suggesting E2 action on the CFA immune response primarily excluded CD16 receptor action.
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PMID:Estrogenic effect on swelling and monocytic receptor expression in an arthritic temporomandibular joint model. 1615 20

Prominent interindividual and sex-dependent differences have been described in responses to sustained pain and other stressful stimuli. Variations in mu-opioid receptor-mediated endogenous opioid neurotransmission may underlie some of these processes. We examined both baseline mu-opioid receptor levels and the activation of this neurotransmitter system during sustained pain using positron emission tomography in a sample of young healthy men and women. Women were studied twice, during low and high estrogen states. The high-estrogen state was associated with regional increases in baseline mu-opioid receptor availability in vivo and a greater activation of endogenous opioid neurotransmission during the pain stressor. The latter did not differ from that obtained in males. During the low estrogen condition, however, significant reductions in endogenous opioid tone were observed at the level of thalamus, nucleus accumbens, and amygdala, which were associated with hyperalgesic responses. Estrogen-associated variations in the activity of mu-opioid neurotransmission correlated with individual ratings of the sensory and affective perceptions of the pain and the subsequent recall of that experience. These data demonstrate a significant role of estrogen in modulating endogenous opioid neurotransmission and associated psychophysical responses to a pain stressor in humans.
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PMID:Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. 1672 35


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