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

The existence of a sex difference in several chronic pain syndromes and the fluctuation of symptoms during the menstrual cycle strongly suggest sex hormones are involved in pain processing. The mechanisms underlying these changes are not well understood. Using the colorectal distention model in the rat, we previously reported a sex difference in the response to distention [Ji Y, Murphy AZ, Traub RJ (2006) Sex differences in morphine induced analgesia of visceral pain are supraspinally and peripherally mediated. Am J Physiol Regul Integr Comp Physiol 291:R307-R314] and that ovariectomy decreased the responses to distention while estrogen replacement reversed the decrease [Ji Y, Murphy AZ, Traub RJ (2003) Estrogen modulates the visceromotor reflex and responses of spinal dorsal horn neurons to colorectal stimulation in the rat. J Neurosci 23:3908-3915], suggesting estrogen increases visceral nociception. In the present study we tested the hypothesis that the visceromotor response to colorectal distention fluctuates with the estrous cycle. Three measurements (vaginal smears, uterine tube weight and plasma estrogen concentration) were used to determine the estrous phase. Comparison of the visceromotor response threshold and magnitude was made between proestrus and metestrus/diestrus. Our experiment demonstrated that the distention threshold was significantly lower in proestrus (median: 15 mm Hg) as compared with metestrus/diestrus (median: 25 mm Hg); and the magnitude of the visceromotor response to graded intensities of colorectal distentions (20, 40, 60, 80 mm Hg) was significantly higher in proestrus. The results indicate that the visceromotor response fluctuates with estrous phase, providing evidence for endogenous estrogen modulation of visceral nociceptive processing that could contribute to sex differences.
 ...
PMID:The visceromotor response to colorectal distention fluctuates with the estrous cycle in rats. 1855 Feb 90

Epidemiologic literatures suggest that temporomandibular joint disorders (TMD) are more prevalent in women than in men. It is affecting approximately 7-15% of the adult population in North America, and 80% of patients treated for TMD are women. The severity of symptoms is also related to the age of the patients. The gender and age distribution of TMD suggests a possible link between its pathogenesis and estrogen. It has been reported that estrogen could influence the development, restitution and metabolism of the temporomandibular joint and associated structures such as bone, cartilage and articular disc. Estrogen can also influence the regulative mechanism of pain. In this article, we will use the hypothesis that the overwhelming majority of patients treated for temporomandibular disorders are women and use the available literature to examine the role of estrogens in TMD.
 ...
PMID:The possible role of estrogen in the incidence of temporomandibular disorders. 1859 50

There is mounting evidence that estrogens act directly on the nervous system to affect the severity of pain. Estrogen receptors (ERs) are expressed by sensory neurons, and in trigeminal ganglia, 17beta-estradiol can indirectly enhance nociception by stimulating expression and release of prolactin, which increases phosphorylation of the nociceptor transducer transient receptor potential vanilloid receptor 1 (TRPV1). Here, we show that 17beta-estradiol acts directly on dorsal root ganglion (DRG) sensory neurons to reduce TRPV1 activation by capsaicin. Capsaicin-induced cobalt uptake and the maximum TRPV1 current induced by capsaicin were inhibited when isolated cultured DRGs neurons from adult female rats were exposed to 17beta-estradiol (10-100 nm) overnight. There was no effect of 17beta-estradiol on capsaicin potency, TRPV1 activation by protons (pH 6-4), and P2X currents induced by alpha,beta-methylene-ATP. Diarylpropionitrile (ERbeta agonist) also inhibited capsaicin-induced TRPV1 currents, whereas propylpyrazole triol (ERalpha agonist) and 17alpha-estradiol (inactive analog) were inactive, and 17beta-estradiol conjugated to BSA (membrane-impermeable agonist) caused a small increase. TRPV1 inhibition was antagonized by tamoxifen (1 microm), but ICI182870 (10 microm) was a potent agonist and mimicked 17beta-estradiol. We conclude that TRPV1 in DRG sensory neurons can be inhibited by a nonclassical estrogen-signalling pathway that is downstream of intracellular ERbeta. This affects the vanilloid binding site targeted by capsaicin but not the TRPV1 activation site targeted by protons. These actions could curtail the nociceptive transducer functions of TRPV1 and limit chemically induced nociceptor sensitization during inflammation. They are consistent with clinical reports that female pelvic pain can increase after reductions in circulating estrogens.
 ...
PMID:17beta-estradiol activates estrogen receptor beta-signalling and inhibits transient receptor potential vanilloid receptor 1 activation by capsaicin in adult rat nociceptor neurons. 1861 18

P2X(3) and P2X(2/3) receptors are expressed in peripheral tissues and dorsal root ganglia (DRG) and participate in peripheral pain. However, the mechanisms underlying P2X receptor-mediated nociception at different ovarial hormone levels has not been examined. In this study, 24 female rats were randomly divided into sham-operated (sham), ovariectomized (OVX), estrogen-treated, and estrogen-progesterone-treated groups with colitis. In each group, the visceromotor reflex (VMR) to colorectal distension was tested and the DRG were harvested for a real-time PCR analysis of P2X(3) and P2X(2) receptor mRNA. In OVX rats with colitis we found that the VMR to colorectal distension and P2X(3) receptor mRNA in DRG were both significantly decreased. Estrogen replacement reversed the decrease. However, neither the VMR nor the P2X(3) mRNA level in DRG from OVX colitis rats was reversed by the complex of estrogen and progesterone. Patch-clamp recording showed that in colitis rats, estradiol rapidly potentiated the sustained and transient currents evoked by ATP to 336+/-49% and 122+/-12% of controls, respectively, in a subpopulation of DRG neurons, which were blocked by ICI 182, 780, an antagonist of the estrogen receptor. Whereas progesterone rapidly inhibited the transient currents induced by ATP to 67+/-10% of control and had no effect on the sustained currents evoked by the same agonist. These results indicate that P2X(3) receptors are likely to be an important contributor to the altered colonic functions in colitis rats, where the underlying mechanisms are closely related to endogenous estrogen modulation.
 ...
PMID:Estrogen altered visceromotor reflex and P2X(3) mRNA expression in a rat model of colitis. 1962 2

Endometriosis is a complex trait with significant environmental and genetic influences that are likely to affect its phenotype. Natural history of the disease varies from one individual to another. The gold standard of surgical diagnosis is limited in accuracy by visibility and recognition of lesions by the attending surgeon. Several lines of evidence suggest that pelvic endometriosis results from the reflux of viable endometrial tissue through the fallopian tubes. Endometriosis is an inflammatory disease that nuclear factor kappa B pathway may play an important role in its pathogenesis. Endometriotic lesions demonstrate increased aromatase expression in association with increased cyclo-oxygenase-2 expression, especially in red lesions which represent earlier stages of inflammation. Estrogen and progesterone receptor expressions vary according to the morphology and the inflammatory status of the endometriotic lesions. Normal endometrial tissue fragments can adhere and implant to peritoneum. Aromatase expression, a possible intrinsic survival factor for endometrial tissue, is inducible in human endometrial fragments by androstenedione at physiological concentrations found in peritoneal fluid. Inflammatory response to ectopic endometrial tissue, which may vary in each individual seems to be important in disease progression. Current therapies for endometriosis include surgical and medical approaches aimed at cytoreduction or hormonal suppression. However, the disease have tendency to recur in many symptomatic women. Although new management approaches are emerging, properly designed clinical trials are desperately needed in treatment of pain and subfertility associated with endometriosis. Future studies should also focus on identifying risk population to develop preventive strategies, since the treatment of endometriosis is costly and challenging.
 ...
PMID:Endometriosis and the role of reproductive medicine. 1974 96

It is now firmly established that estrogen and all sex steroid receptors exist in discrete cellular pools outside the nucleus. Estrogen receptors (ER) have been localized to the plasma membrane where both ERalpha and ERbeta function in a wide variety of cells and organs. ERs have also been found in discrete cytoplasmic organelles including mitochondria and the endoplasmic reticulum. In ligand-dependent fashion, each ER pool contributes to the overall, integrated effects of estrogens producing biological outcomes. This review highlights the recent work establishing new roles and targets of membrane ER signaling. Such actions include prevention of vascular injury or cardiac hypertrophy, sexual behavior and pain perception mediated through the central nervous system, osteoblast survival, and fluid resorption in the colon.
 ...
PMID:Plasma membrane estrogen receptors. 1978 54

Bisphenol A (BPA), a chemical estrogen widely used in the food-packaging industry and baby bottles, is recovered in human fluids (0.1-10 nM). Recent studies have reported that BPA is hormonally active at low doses, emphasizing the debate of a risk for human health. Estrogen receptors are expressed in the colon, and although the major route of BPA exposure is food, the effects on gut have received no attention. We first examined the endocrine disrupting potency of BPA on colonic paracellular permeability (CPP), experimental colitis, and visceral sensitivity in ovariectomized rats orally exposed to 5 mg/kg/d BPA (i.e., the no observed adverse effect level), 50 microg/kg/d BPA (i.e., tolerable daily intake), or lower doses. BPA dose-dependently decreased basal CPP, with a half-maximal inhibitory dose of 5.2 microg/kg/d, 10-fold below the tolerable daily intake. This correlated with an increase in epithelial tight junction sealing, also observed in Caco-2 cells exposed to 10 nM BPA. When ovariectomized rats were fed with BPA at the no observed adverse effect level, the severity of colitis was reduced, whereas the same dose increased pain sensitivity to colorectal stimuli. We then examined the impact of perinatal exposure to BPA on intestinal permeability and inflammatory response in the offspring. In female rats, but not in male rats, perinatal BPA evoked a decrease of CPP in adulthood, whereas the proinflammatory response of colonic mucosa was strengthened. This study first demonstrates that the xenoestrogen BPA at reference doses influences intestinal barrier function and gut nociception. Moreover, perinatal exposure promotes the development of severe inflammation in adult female offspring only.
 ...
PMID:Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats. 2001 22

One of the many harmful factors faced by the skin is solar UV radiation, which damages skin by inducing chronic low-grade inflammation through increased expression of proinflammatory cytokines, metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). Estrogen receptors (ERs) alpha and beta are ligand-dependent transcription factors that are expressed in skin, and an ERbeta agonist has previously shown efficacy in vivo in models of pain and inflammation. Because ERbeta does not carry the breast and uterine proliferation liabilities of ERalpha, we decided to explore the possibility of using ERbeta as a target for photoaging. We show that ERbeta-selective compounds suppressed the expression of cytokines and MMPs in activated keratinocytes and fibroblast-based in vitro models of photoaging. Furthermore, in activated dermal fibroblasts, ERbeta-selective compounds also inhibited COX-2. These activities of ERbeta ligands in skin cells correlated with the expression levels of ERbeta and showed reversal by treatment with a potent synthetic ER antagonist. Furthermore, the pharmacology of ERbeta-selective compound was observed in wild-type but not in skin cells obtained from ERbeta knockout mice. Finally, we demonstrate that a synthetic ERbeta agonist inhibited UV-induced photodamage and skin wrinkle formation in a murine model of photoaging. Therefore, the potential of an ERbeta ligand to regulate multiple pathways underlying the cause of photoaging suggests ERbeta to be a novel therapeutic target for the prevention and treatment of photoaging.
 ...
PMID:Estrogen receptor beta is a novel therapeutic target for photoaging. 2011 Apr 5

While a number of chronic pain conditions are much more prevalent in women than men, the role of estrogen in regulating nociception remains unclear. Estrogen receptors (ER) are known to be expressed in various parts of the nociceptive pathway, including in the small-sized primary sensory neurons of the dorsal root ganglion (DRG). This study evaluated the effects of long term estrogen replacement on pain sensitivity and neuropeptide expression in the DRG of female Sprague Dawley rats. The goal was to evaluate whether estrogen modulates nociceptive neuropeptides in the DRG in a manner consistent with its effects on pain sensitivity. Our results show that long term (28 days) ovariectomy (ovx) of adult rats induces a profound thermal and mechanical hyperalgesia of the hindpaw and tail compared to ovariectomized animals that were continuously estrogen-treated (ovx+E). Significant changes in the expression of two neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP), were observed using immunocytochemistry and in situ hybridization (ISH) in the small lumbar DRG neurons which contain ER. CGRP and SP were differentially regulated by estrogen, with SP showing a significant downregulation at both the peptide and mRNA levels while CGRP and its mRNA were increased in the DRG of estrogen-treated animals. We also evaluated the development of mechanical allodynia after partial sciatic nerve injury and found that both ovx and ovx+E animals developed significant allodynia within a week of the partial nerve injury, which continued for at least one month. The estrogen-treated animals showed a partial amelioration of the extent of the allodynia at 2 weeks post injury. Overall, the results suggest that estrogen has significant anti-nociceptive actions that can be directly correlated with changes in expression of two peptides in the small nociceptive ERalpha expressing neurons of the DRG.
 ...
PMID:Estrogen effects on pain sensitivity and neuropeptide expression in rat sensory neurons. 2030 52

Estradiol is a neuroactive steroid found in several brain areas such as locus coeruleus (LC). It modulates nociception by binding to its receptors and also by allosteric interaction with other membrane-bound receptors like glutamate and GABA(A) receptors. LC is involved in noradrenergic descending pain modulation. In order to study the effect of 17beta-estradiol on both acute and persistent pain modulation and its mechanisms, formalin was injected into the male rat's hind paw. Formalin-induced responses including licking, flexing duration and paw jerking frequency were recorded for 60 min after injection of 50 microl of 2% formalin. The results of the current study showed that intra-locus coeruleus injection of 17beta-estradiol attenuated the second phase, but not the acute phase of formalin-induced pain (P<0.05). AMPA receptor antagonists CNQX had no effect on pain-modulatory effect of 17beta-estradiol. Estrogen and GABA(A) receptor antagonists (ICI 182,780 and bicuculline, respectively) could not reverse the antinociceptive effect of 17beta-estradiol. However, NMDA receptor antagonist APV significantly antagonized the analgesic effect of 17beta-estradiol on flexing behaviour (P<0.05). It may be concluded that the analgesic effect of 17beta-estradiol in formalin-induced inflammatory pain is mediated through interaction with membrane-bound receptors, probably the NMDA receptors.
 ...
PMID:The effect of intra-locus coeruleus injection of 17beta-estradiol on inflammatory pain modulation in male rat. 2060 Mar 51


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>