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)

Clinical and preclinical studies have found sex-specific differences in the discrimination and perception of inflammatory stimuli. The emerging picture suggests that the biological basis of these differences resides in the regulatory activity of gonadal hormones in the central nervous system. This study describes the effects of ovarian hormones in inflammatory pain processes. Ovariectomized rats received estradiol and/or progesterone, and the number of paw flinches was measured after 1, 2.5 or 5% formalin administration. Both estradiol and progesterone altered the number of flinches only after 1% formalin administration. Estradiol significantly reduced the overall number of flinches during Phase II of the formalin nociceptive response while progesterone attenuated Phase I of the response. After co-administration of estradiol and progesterone, progesterone reversed estradiol's analgesic effect in Phase II, however, estradiol did not reverse progesterone's analgesic activity in Phase I. To determine if estradiol effects are receptor-mediated, tamoxifen (selective estrogen receptor mediator, 15 mg/kg) or alpha-estradiol (an inactive isomer of estradiol, 20 microg) were utilized. Tamoxifen decreased the number of formalin-induced flinches during Phase II while alpha-estradiol did not affect any formalin-induced responses. When co-administered with estradiol, tamoxifen failed to reverse estradiol's effect, suggesting both tamoxifen and estradiol activate similar intracellular mechanisms. Although Western blot analysis detected the presence of estradiol alpha and beta and progesterone B receptors in the spinal cord, hormone replacement treatments had no effects on the levels of these receptors. We postulate that the mechanisms by which estradiol and progesterone induce analgesia occur through the activation of their receptor at the spinal cord level.
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PMID:Estradiol and progesterone differentially regulate formalin-induced nociception in ovariectomized female rats. 1625 5

Stimulation of the uterine cervix at parturition activates neural circuits involving primary sensory nerves and supraspinally projecting neurons of the lumbosacral spinal cord, resulting in output of hypothalamic neurohormones. Dorsal root ganglia (DRG) and spinal neurons of these circuits are not well-characterized. The objectives of this study were to detail the activation of DRG and spinal neurons of the L6/S1 levels that are stimulated at late pregnancy, verify hypothalamic projections of activated spinal neurons, and determine whether activated neurons express estrogen receptor-alpha (ERalpha). Expression of phosphorylated cyclic-AMP response element-binding protein (PCREB) and Fos immunohistochemistry were used to "mark" activated DRG and spinal neurons, respectively. Retrograde tracing identified uterine-cervix-related and spinohypothalamic neurons. Baseline PCREB expression in the DRG increased during pregnancy and peaked during the last trimester. Some PCREB-expressing neurons contained retrograde tracer identifying them as cervix-related neurons. Fos-expressing neurons were few in spinal cords of nonpregnant and day 22 pregnant rats but were numerous in parturient animals. Some Fos-expressing neurons located in the dorsal half of the spinal cord contained retrograde tracer identifying them as spinohypothalamic neurons. Some DRG neurons expressing PCREB also expressed ERalpha, and some spinal neurons activated at parturition projected axons to the hypothalamus and expressed ERalpha. These results indicate that DRG and spinal cord neurons are activated at parturition; that those in the spinal cord are present in areas involved in autonomic and sensory processing; that some spinal neurons project axons to the hypothalamus, ostensibly part of a neuroendocrine reflex; and that sensory and spinal neurons can respond to estrogens. Moreover, some activated sensory neurons may be involved in the animal's perception of labor pain.
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PMID:Activation and circuitry of uterine-cervix-related neurons in the lumbosacral dorsal root ganglia and spinal cord at parturition. 1627 43

Injury to the spinal nerves of mice induces allodynia and hyperalgesia. Intrathecal injection of the progesterone/estrogen receptor antagonist ICI 182,780 produced antinociceptive effects. Co-administration of estrogen did not reduce but tended to enhance the antinociceptive effect of ICI 182,780. On the other hand, co-administration of progesterone dose-dependently reduced the antinociceptive effect of ICI 182,780, indicating that the antinociceptive effect is through antiprogesterone receptor activity of ICI 182,780. These results suggest that spinal progesterone receptors play an important role in neuropathic pain, and that controlling the activity of progesterone receptors may be of great importance in the treatment of neuropathic pain.
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PMID:Progesterone receptor antagonist is effective in relieving neuropathic pain. 1675 51

A rare case of the inguinal endometriosis was reported with immunohistochemical analysis. A 28-year-old woman had a thumb-sized tumor in the right groin for two years with a gradual increase in size and pain. An operation revealed an elastic hard tumor with an unclear margin and adhesion to the uterine round ligament. The histology showed irregular proliferation of the endometrial glands and stroma. The glandular epithelium stained weakly positive against CD125 antibody and the stromal matrix stained strongly positive against CD10 antibody. The nucleus in both the epithelial and stromal cells stained strongly positive against progesterone and estrogen receptor antibodies, and the cytoplasm in both types of cells stained moderately positive against COX-2 (cyclooxygenase-2) antibody. In conclusion, the combination of estrogen or progesterone receptor antibody for the nucleus and CD10 or COX-2 antibody for the cytoplasm could enhance the accuracy of diagnosis for ectopic endometriosis.
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PMID:Immunohistochemical analysis of an ectopic endometriosis in the uterine round ligament. 1696 27

ERB-041 (2-(3-Fluoro-4-hydroxyphenyl)-7-vinyl-1,3 benzoxazol-5-ol) is a selective estrogen receptor-beta agonist with activity in rodent models of rheumatoid arthritis and endometriosis. Clinical trials for these diseases are underway: however, the role of estrogen receptor-beta in modulating pain associated with inflammation remains unknown. These studies demonstrate that acutely administered ERB-041 is anti-hyperalgesic in preclinical models of chemical-induced and acute inflammatory pain, thus suggesting that ERB-041 may be useful for modulating pain associated with some types of inflammation.
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PMID:An estrogen receptor-beta agonist is active in models of inflammatory and chemical-induced pain. 1705 36

Aromatase inhibitors (AIs) are widely used as an adjuvant endocrine treatment in postmenopausal women with early-stage breast cancer. Clinical trials have assessed 5 years of AI therapy, either as an alternative to tamoxifen for primary adjuvant therapy of breast cancer, or after 5 years of adjuvant tamoxifen. Treatment of 2-3 years' duration after 2-3 years of tamoxifen has also been studied. AI therapy brings side effects related to estrogen deprivation, and this side effect profile differs in clinically relevant ways from that seen with tamoxifen. In particular, the selective estrogen receptor modulatory effects of tamoxifen contribute to menopausal symptoms, vaginal discharge, and the rare but worrisome risks of thromboembolism and uterine carcinoma. By contrast, the low levels of estrogen achieved with aromatase inhibition contribute to menopausal symptoms, vaginal dryness and sexual dysfunction, and accelerated bone demineralization with risk of osteoporosis and osteoporotic fracture. Clinical experience also suggests that AI therapy is associated with a novel musculoskeletal side effect consisting of an arthralgia syndrome. The actual incidence of AI-associated arthralgias or musculoskeletal symptoms is not known, though such symptoms are quite prevalent and appear more commonly with AI use than with tamoxifen. Arthralgias can be a reason for discontinuation of AI treatment. The possible mechanisms of AI-associated arthralgia are unclear. Estrogen deficiency causes bone loss, which in turn contributes to arthralgia. Less well-studied functions of estrogen include regulating immune cells and cytokines involved in bone remodeling, and modulating pain sensitivity at the level of the central nervous system. Arthralgia and arthritis have seldom been rigorously differentiated in clinical trials of AIs. Assessment of inflammatory and rheumatologic markers, as well as detailed evaluation of patient symptoms using appropriate quality-of-life instruments, may be warranted in order to understand both the symptoms and the etiology of the arthralgia syndrome. Treatment options for arthralgia (primarily non-steroidal anti-inflammatory drugs) are currently inadequate, but areas of active research include high-dose vitamin D and new-targeted therapies to inhibit bone loss.
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PMID:Aromatase inhibitor-associated arthralgia syndrome. 1736 3

Endometriotic nodules in the lower genital tract often cause dysmenorrhea and dyspareunia. We report here a case of posterior vaginal fornix endometriosis that was overlooked for several years. We performed a trans-vaginal resection after the associated pain was not relieved by repetitive gonadotropin-releasing hormone agonist (GnRHa) therapy or abdominal surgery. After the resection, the patient's symptoms disappeared. The patient subsequently conceived and proceeded to a full-term delivery. The pathological diagnosis was 'endometriosis of the vagina.' Immunohistochemical staining revealed that the progesterone receptor-positive cells outnumbered the estrogen receptor-positive cells. We emphasize that the existence of vaginal lesions should be considered in cases in which pain has not improved despite long-term GnRHa administration, or in cases involving dyspareunia. To provide appropriate treatment, attentive evaluation and careful examination of the disease are necessary for a patient with prolonged unsatisfactory progress.
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PMID:Clinical pitfalls of pain recurrence in endometriosis arising in the posterior vaginal fornix. 1744 98

The histology of the primary tumor in metastatic spine disease plays an important role in its treatment and prognosis. However, there is paucity in the literature of histology-specific analysis of spinal metastases. In this study, prognostic variables were reviewed for patients who underwent surgery for breast metastases to the spinal column. Respective chart review was done to first identify all patients with breast cancer over an 8-year period at a major cancer center and then to select all those with symptomatic metastatic disease to the spine who underwent spinal surgery. Univariate and multivariate analyses were used to assess several prognostic variables. Presence of visceral metastases, multiplicity of bony lesions, presence of estrogen receptors (ER), and segment of spine (cervical, thoracic, lumbar, sacral) in which metastases arose were compared with patient survival. Eighty-seven patients underwent 125 spinal surgeries. Those with estrogen receptor (ER) positivity had a longer median survival after surgery compared to those with estrogen receptor negativity. Patients with cervical location of metastasis had a shorter median survival compared with those having metastases in other areas of the spine. The presence of visceral metastases or a multiplicity of bony lesions did not have prognostic value. In patients with spinal metastases from breast cancer, aggressive surgical management may be an option for providing significant pain relief and preservation/improvement of neurological function. Interestingly, in patients undergoing such surgery, cervical location of metastasis is a negative prognostic variable, and ER-positivity is associated with better survival, while presence of visceral or multiple bony lesions does not significantly alter survival.
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PMID:Positive and negative prognostic variables for patients undergoing spine surgery for metastatic breast disease. 1748 76

Aromatase inhibitors are recommended for use by postmenopausal women who have estrogen receptor-positive early-stage breast cancer. They reduce local and distant recurrence more effectively than tamoxifen. Anastrozole (Arimidex, AstraZeneca Pharmaceuticals LP), letrozole (Femara, Novartis Pharmaceuticals Corporation), and exemestane (Aromasin, Pfizer Inc.) inhibit aromatase activity, thus significantly decreasing estrogen production in tissues such as liver, muscle, and fat. Very low levels of estrogen may be one cause of musculoskeletal pain, a common side effect associated with the drugs. In the major adjuvant aromatase inhibitor clinical trials, 25%-30% of the patients enrolled experienced musculoskeletal pain. Although quality-of-life studies demonstrate that aromatase inhibitors are well tolerated overall, some women discontinue this treatment because of musculoskeletal pain. Little is known about how to predict, measure, or manage musculoskeletal pain caused by aromatase inhibition. Oncology nurses play an important role in the assessment and management of side effects related to cancer. This article provides an overview of the current knowledge about musculoskeletal pain in patients with breast cancer receiving aromatase inhibitor therapy.
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PMID:Aromatase inhibitors and musculoskeletal pain in patients with breast cancer. 1762 27

Women have greater temporal summation of experimental pain stimuli and also have a higher propensity for developing chronic visceral pain conditions. Sex hormone-mediated regulation of N-methyl-d-aspartic acid receptors (NMDARs) in nociceptive pathways is a plausible mechanism that may underlie these phenomena. The aim of this study was to compare the effect of 17-beta-estradiol (E2) in modulation of NMDAR activity in adult male and female rat dorsal root ganglia (DRG) neurons. DRG neurons were collected from adult male or female rats and grown in short-term culture in steroid-free media. NMDAR currents were recorded on small to medium size neurons by whole cell patch clamp using rapid perfusion with saturating concentrations of N-methyl-d-aspartic acid and glycine in the absence of extracellular Mg(2+). We found that the average density of NMDAR currents was 2.8-fold larger in DRG neurons from female rats compared with male rats (P<0.0001). Addition of 100 nM E2 increased NMDAR currents 55+/-15% in female neurons, but only 19+/-7% in male neurons. Potentiation was maximal after 20-40 min and dose dependent with an apparent 50% excitatory concentration of 17-23 nM. This effect was mimicked by E2 conjugated to BSA and attenuated by pretreatment with the protein tyrosine kinase inhibitor lavendustin A (1 microM) or the estrogen receptor (ER) antagonist, ICI 182,780 (1 microM), strongly suggesting activation of a cell surface ER acting through a non-genomic mechanism involving protein tyrosine kinases to increase NMDAR currents. These results identify sex-based differences in both the basal expression and the regulation of the NMDARs in DRG neurons.
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PMID:Sex-dependent differences in the activity and modulation of N-methyl-d-aspartic acid receptors in rat dorsal root ganglia neurons. 1769 30


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