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)

Bicalutamide is a competitive nonsteroidal androgen receptor antagonist. In the European Union and a number of other countries, bicalutamide 150 mg per day is approved as an adjuvant to primary treatments (radical prostatectomy or radiotherapy) or as monotherapy as an alternative to surgical or medical castration in men with locally advanced, nonmetastatic prostate cancer. The ongoing bicalutamide Early Prostate Cancer (EPC) program has shown that breast events, defined as gynecomastia, breast pain or both, are a significant limitation of bicalutamide. Nearly 90% of patients experienced one or both symptoms and nearly 16% of patients withdrew from the EPC program as a consequence of bicalutamide-induced breast events. Tamoxifen, anastrozole and radiotherapy have all been studied as options for the treatment of breast events. To date, tamoxifen appears to be the superior agent in terms of outcomes; however, further studies are still required to determine the optimal dose and timing of tamoxifen administration for both prophylaxis and treatment. In addition, the impact on prostate cancer control remains uncertain. An ongoing clinical trial using toremifene to prevent morphometric vertebral fractures in men undergoing medical and/or surgical castration will provide some additional data on the effects of selective estrogen receptor modulators in men with prostate cancer.
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PMID:Treatment of bicalutamide-induced breast events. 1806 51

Many painful conditions occur more frequently in women, and estrogen is a predisposing factor. Estrogen may contribute to some pain syndromes by enhancing axon outgrowth by sensory dorsal root ganglion (DRG) neurons. The objective of the present study was to define mechanisms by which estrogen elicits axon sprouting. The estrogen receptor-alpha agonist propyl pyrazole triol induced neurite outgrowth from cultured neonatal DRG neurons, whereas the estrogen receptor-beta agonist diarylpropionitrile was ineffective. 17beta-Estradiol (E2) elicited sprouting from peripherin-positive unmyelinated neurons, but not larger NF200-positive myelinated neurons. Microarray analysis showed that E2 up-regulates angiotensin II (ANGII) receptor type 2 (AT2) mRNA in vitro, and studies in adult rats confirmed increased DRG mRNA and protein in vivo. AT2 plays a central role in E2-induced axon sprouting because AT2 blockade by PD123,319 eliminated estrogen-mediated sprouting in vitro. We assessed whether AT2 may be responding to locally synthesized ANGII. DRG from adult rats expressed mRNA for renin, angiotensinogen, and angiotensin converting enzyme (ACE), and protein products were present and occasionally colocalized within neurons and other DRG cells. We determined if locally synthesized ANGII plays a role in estrogen-mediated sprouting by blocking its formation using the ACE inhibitor enalapril. ACE inhibition prevented estrogen-induced neuritogenesis. These findings support the hypothesis that estrogen promotes DRG nociceptor axon sprouting by up-regulating the AT2 receptor, and that locally synthesized ANGII can induce axon formation. Therefore, estrogen may contribute to some pain syndromes by enhancing the pro-neuritogenic effects of AT2 activation by ANGII.
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PMID:Estrogen elicits dorsal root ganglion axon sprouting via a renin-angiotensin system. 1838 95

Neurobehavioral investigations into the functions of estrogen receptor (ER)alpha and ERbeta have utilized 'knockout' mice, phytoestrogens and, more recently, ER-specific agonists. Feeding, sexual, aggressive and social behavior, anxiety, depression, drug abuse, pain perception, and learning (and associated synaptic plasticity) are affected by ERalpha and ERbeta in a manner that is dependent upon the specific behavior studied, gender and developmental stage. Overall, ERalpha and ERbeta appear to function together to foster sociosexual behavior while inhibiting behaviors that, if occurring at the time of behavioral estrous, may compete with reproduction (eg, feeding). Recently developed pharmacological tools have limited selectivity and availability to the research community at large, as they are not commercially available. The development of highly selective, commercially available ERbeta-specific antagonists would greatly benefit preclinical and applied research.
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PMID:Estrogen receptor beta agonists in neurobehavioral investigations. 1860 May 82

The nature of the distinctive ovarian lesion often associated with sclerosing peritonitis, initially considered a variant of luteinized thecoma in the paper describing this phenomenon, remains uncertain, as does its long-term prognosis. We describe the features of 27 cases, including immunohistochemical analysis of 13 cases. Sclerosing peritonitis was documented in 25 cases. Patients ranged in age from 10 months to 85 years, and typically presented with abdominal distension and pain with ascites and sometimes bowel obstruction. The ovarian lesions, clinically bilateral in 24 cases, ranged from 2 to 31 cm and often had a striking cerebriform aspect. Microscopically, mitotically active spindle cells with weakly luteinized cells, variable edema, and entrapped follicles were typical. The spindle cells were focally positive with calretinin in 2 cases, CD56 in 2, AE1/3 in 4, smooth muscle actin in 12, and desmin in 8 cases, and negative with alpha-inhibin, epithelial membrane antigen, beta-catenin, CD34, and transforming growth factor-beta, with focal nuclear positivity for estrogen receptor in 5 and progesterone receptor in 11 cases. Luteinized cells were positive with alpha-inhibin, calretinin, and/or CD56. The peritoneal lesions were strongly positive with AE1/3 and exhibited focal weak or moderate positivity with estrogen receptor or progesterone receptor in 4 of 8 cases each. Follow-up in 20 cases (mean: 5.9 y) disclosed no evidence of spread of the ovarian lesion, but 3 patients died of sclerosing peritonitis. The findings fail to allow definitive classification of the ovarian lesions, and we prefer at present to retain their current designation as a subtype of luteinized thecoma, but to allow for the possibility of a non-neoplastic nature, feel it reasonable to have the designation "thecomatosis" as a parenthetical alternative. We have documented for the first time that sclerosing peritonitis is not invariably associated with the distinctive ovarian pathology present in these cases.
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PMID:Luteinized thecomas (thecomatosis) of the type typically associated with sclerosing peritonitis: a clinical, histopathologic, and immunohistochemical analysis of 27 cases. 1863 18

Clinical and basic studies demonstrate that estrogen (E-sub-2)-based therapies influence anxiety and mood, but the receptor targets (e.g., a or ss isoform of the estrogen receptor, ER) for these effects requires further investigation. To address the specificity of E2's anxiolytic-like effects through ERss, anxiety, motor, and nociceptive behavior of ovariectomized, wildtype (WT), and ERss knockout (ssERKO) mice was examined. Mice were administered oil vehicle or ER agonists, 17ss-E2 (E2; 0.1 mg/kg; similar affinity for ERa and ERss), and a selective ER modulator, diarylpropionitrile (DPN; 0.1 mg/kg; greater affinity for ERss than ERa). Performance of mice in anxiety (open field, elevated plus maze, elevated zero maze, social interaction), motor activity (activity monitor) and nociception (tailflick, pawlick) measures was compared. Results supported our hypothesis that ERss is important in modulation of anxiety-like behavior by E2 in some tasks. Administration of E2 or DPN to WT, but not ssERKO, mice increased open field central entries, plus maze open arm time, zero maze open quadrant time, and social interaction. This pattern was neither seen in motor activity nor pain threshold measures. Thus, actions of ERss may be important for modulating anxiety-like behavior of mice.
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PMID:Estradiol or diarylpropionitrile decrease anxiety-like behavior of wildtype, but not estrogen receptor beta knockout, mice. 1882 54

A new approach to menopausal therapy is the tissue selective estrogen complex or the pairing of a selective estrogen receptor modulator with estrogens. The clinical profile of a tissue selective estrogen complex will result from the blended tissue-selective activities of its components. An appropriate tissue selective estrogen complex may provide the therapeutic benefits of estrogens and selective estrogen receptor modulators with better tolerability and safety than either therapy alone. An ideal menopausal therapy would reduce the number and severity of hot flashes, effectively treat vulvar-vaginal atrophy and its symptoms, prevent and treat menopausal osteoporosis, and have favorable effects on lipoprotein profiles, while at the same time would not stimulate the endometrium, not cause uterine bleeding, not increase the risk of vascular events, not be associated with breast pain or tenderness, and potentially reduce breast cancer incidence. Here, we introduce the concept of a tissue selective estrogen complex and the rationale for its development as a next generation menopausal therapy.
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PMID:A new approach to menopausal therapy: the tissue selective estrogen complex. 1908 68

We examined nociceptive responses to mechanical stimulation in mice of both sexes lacking the estrogen receptor alpha or beta and in respective wild types under normal conditions, after inflammation of a hindpaw or peripheral nerve injury. In normal wild-type mice, females had significantly lower paw withdrawal threshold than males. There was no significant difference between wild-type mice and knock-outs of either estrogen receptor alpha or beta in mechanical response threshold in male mice. However, significantly elevated response threshold was observed in both knock-out female mice, which eliminated sex differences in nociception. After carrageenan-induced inflammation of a hindpaw, all wild-type and knock-out mice exhibited similar local edema with no difference between the sexes. Wild-type mice developed hypersensitivity (allodynia) to mechanical stimulation, which was more profound in the females than in males. Again, such sex difference was not observed in the knock-outs of either estrogen receptor. Photochemically induced partial sciatic nerve injury caused similar persistent mechanical hypersensitivity in the wild types and both estrogen receptor knock-outs with no difference between the sexes. These results suggest that the sex difference in basal mechanical pain threshold and inflammatory hypersensitivity is eliminated in mice lacking either the estrogen alpha receptors or beta receptors. However, these receptors do not seem to be directly involved in mediating pain sensitivity in general or in the development of neuropathic pain. It is unclear whether the elimination of sex differences observed in the knock-outs reflects an ongoing effect of estrogen acting through its receptors in females or the developmental changes that predominantly affect females.
Pain 2009 May
PMID:Ablation of estrogen receptor alpha or beta eliminates sex differences in mechanical pain threshold in normal and inflamed mice. 1928 5

Pelvic endometriosis in women is a very common disease. The incidence of this condition in Poland in reproductive age women is about 7-15%, and as much as 50% of cases is diagnosed in patients with co-existing infertility and/or pain and adhesion of a true pelvis. The choice of a therapeutic method depends on the patient's age, stage of the disease, desire for pregnancy, the presence of adhesion, focus localization and a reaction to previous treatment. Currently, the most popular is surgical treatment sometimes followed by pharmacotherapy. Pharmacological treatment includes hormone therapy and symptomatic treatment, also the use of painkillers. Hormonal agents are administered to suppress ovarian activity and cause atrophy of ectopic foci of endometrium. At present, post-surgical pharmacotherapy for endometriosis uses mainly such hormones as: the Combined Oral Contraceptive Pill (COCP), progestagens, danazol, GnRh (gonadotropin-releasing hormone) analogues, aromatase inhibitors and other less common drugs. Also other therapeutic procedures are recommended in endometriosis treatment, procedures which support and in certain clinical situations even replace classical pharmacological methods. Some of them are immunotherapy and a diet rich in isoflavones, organic compounds which modulate estrogen receptor activity. Numerous clinical trials proved that preoperative pharmacotherapy does not improve treatment results and is not applicable to endometriomas in women. On the other hand, postoperative pharmacotherapy still ignites controversy. As maintained by the most recent literature, in the case of mild endometriosis (clinical Stage I and II according to the American Society for Reproductive Medicine) endometrial ablation has better effects than observation only, however postoperative pharmacotherapy does not improve the results of treatment. In more severe cases (clinical Stage III and IV), the best results are achieved by the combined treatment. Nevertheless, no randomized research has been carried out on a wide scale in this group of patients.
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PMID:[Pharmacotherapy for pelvic endometriosis in women]. 1938 39

Estrogens exert a substantial influence on the transmission of nociceptive stimuli and the susceptibility to pain disorders as made evident by studies in both animals and human subjects. The estrogen receptor (ER) seems to be of crucial importance to the cellular mechanisms underlying such an influence. However, it has not been clarified whether nociceptive neurons activated by pain express ERs. In this study, a noxious injection of formalin was given into the lower lip of female rats, thereby activating nociceptive neurons in the trigeminal subnucleus caudalis as demonstrated by immunohistochemical labeling of Fos. Using a dual-label immunohistochemistry protocol ERalpha-containing cells were visualized in the same sections. In the superficial layers of the medullary dorsal horn, 12% of ERalpha-labeled cells, mainly located in lamina II, also expressed noxious-induced Fos. These findings show that nociceptive-responsive neurons in the medullary dorsal horn express ERalpha, thus providing a possible morphological basis for the hypothesis that estrogens directly regulate pain transmission at this level.
Eur J Pain 2010 Mar
PMID:Estrogen receptor-alpha expression in nociceptive-responsive neurons in the medullary dorsal horn of the female rat. 1952 33

Cyclin-dependent kinase-5 (Cdk5), a proline-directed serine/threonine kinase, may alter pain-related neuronal plasticity by regulating extracellular signal-related kinase-1/2 (ERK1/2) activation. This study investigated whether Cdk5-dependent ERK activation underlies the estrogen-elicited facilitation on the repetitive stimulation-induced spinal reflex potentiaton (SRP) that is presumed to be involved in postinflammatory/neuropathic hyperalgesia and allodynia. Reflex activity of the external urethra sphincter electromyogram evoked by pelvic afferent nerve test stimulation (TS; 1 stimulation/30 s for 10 min) and repetitive stimulation (RS; 1 stimulation/1 s for 10 min) was recorded in anesthetized rats. TS evoked a baseline reflex activity, whereas RS produced SRP. Intrathecal (it) beta-estradiol facilitated the repetitive stimulation-induced SRP that was reversed by pretreatment with the estrogen receptor anatogonist ICI 182,780 (10 nM, 10 microl it), Cdk5 inhibitor roscovitine (100 nM, 10 microl it), ERK inhibitor (U-0126; 100 microM, 10 microl it) and N-methyl-D-aspartate (NMDA) NR2B subunit antagonist (Co-101244; 100 nM, 10 microl it). Moreover, ERalpha (propylpyrazoletriol; 100 nM, 10 microl it) and ERbeta (diarylpropionitrile; 100 microM, 10 microl it) agonists both facilitated the SRP, similar to results with a beta-estradiol injection. In association with the facilitated RS-induced SRP, an intrathecal beta-estradiol injection elicited ERK1/2 and NR2B subunit phosphorylation that were both reversed by intrathecal roscovitine and U-0126. These results indicated that the Cdk/ERK cascade, which is activated by ERalpha and ERbeta, may subsequently phosphorylate the NR2B subunit to develop NMDA-dependent postinflammatory hyperalgesia and allodynia to maintain the protective mechanisms of the body.
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PMID:Estrogen-dependent facilitation on spinal reflex potentiation involves the Cdk5/ERK1/2/NR2B cascade in anesthetized rats. 1953 42


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