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

The anatomy of the human uterine vascular tree changes repeatedly with the variations in hormonal state during each menstrual cycle, with progressive differentiation of arterioles up to the premenstrual state. Hormonal factors also influence the innervation of uterine arteries, both cholinergic, adrenergic and peptidergic, and regulate the spontaneous contractile activity of the smooth muscle of vessel walls as well as the motor responses of these tissues to different vasoactive substances. The smaller branches of uterine arteries, i.e., the resistance arteries appear to be of particular importance in the regulation of uterine blood flow, since they are most densely innervated. Furthermore, the most effective uterine vasoconstrictors in vitro, vasopressin, endothelin, oxytocin and noradrenaline have a more pronounced effect on these vessels than on the main branches of the uterine artery. Vascular compression may also result from changes in the myometrial activity. A hormonal disturbance may cause dysfunctional bleeding by changing vessel growth as well as the uterine smooth muscle activity of both vessels and myometrium. An example of the latter phenomenon is primary dysmenorrhoea, women with this condition having an increased secretion of vasopressin. By an action on type V1 vasopressin receptors of the uterus, this peptide causes myometrial hyperactivity and vasoconstriction, with resultant uterine ischemia and pain. Further support for a pathophysiological role of vasopressin and also of oxytocin in dysmenorrhoea is the therapeutic effect of a competitive type V1 vasopressin and oxytocin receptor antagonist in the condition.
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PMID:Vascularization of human endometrium. Uterine blood flow in healthy condition and in primary dysmenorrhoea. 797 51

Arginine vasopressin (AVP) activates three vasopressin receptors and it also has an agonistic activity on the oxytocin receptor. For an accurate description of the target receptor subtype(s) responsible for complex AVP and oxytocin actions, a careful evaluation of ligand specificity and receptor activities are required, particularly when these receptors are co-expressed in the central nervous system. Previous studies suggest that AVP plays a regulatory role in nociception through the direct activation of central vasopressin receptors and also through the receptors that reside in the peripheral tissues. Genetically altered rodent models, including the AVP-deficient mutant Brattleboro rat and gene knockout mice lacking an endogenous opioid peptide, advanced the understanding of the interactions between the pain perception process and AVP system. This report reviews previous findings in this important field and reconciles them with the findings of recent gene knockout/knockdown studies.
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PMID:New topics in vasopressin receptors and approach to novel drugs: vasopressin and pain perception. 1915 39

It has been recently demonstrated that pain behavior in the mouse can be modulated by the presence of a conspecific, but what remains unclear is whether such pain behavior can serve the function of soliciting social approach. Using a novel social approach paradigm, we tested mice in various dyadic or triadic conditions, including "jailed" mice-some in pain via intraperitoneal injection of 0.9% acetic acid-and test mice free to approach or avoid the jailed mice. We observed a sex-specific effect whereby female, but not male, test mice approached a familiar same-sex conspecific in pain more frequently than an unaffected familiar or unfamiliar, but affected, conspecific. Despite a substantial literature emphasizing oxytocin's role in affiliative and pair-bonding behavior, this effect was also observed in female mice lacking the oxytocin receptor, suggesting that pain-related social approach may not be mediated by oxytocin. Furthermore, we found that the frequency of contact by the test mouse was negatively correlated with the pain behavior of the jailed mouse, suggesting that proximity of a familiar unaffected conspecific may have analgesic properties.
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PMID:Social approach to pain in laboratory mice. 1984 45

The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) contribute to the regulation of diverse cognitive and physiological functions including nociception. Indeed, OXT has been reported to be analgesic when administered directly into the brain, the spinal cord, or systemically. Here, we characterized the phenotype of oxytocin receptor (OTR) and vasopressin-1A receptor (V1AR) null mutant mice in a battery of pain assays. Surprisingly, OTR knock-out mice displayed a pain phenotype identical to their wild-type littermates. Moreover, systemic administration of OXT dose-dependently produced analgesia in both wild-type and OTR knock-out mice in three different assays, the radiant-heat paw withdrawal test, the von Frey test of mechanical sensitivity, and the formalin test of inflammatory nociception. In contrast, OXT-induced analgesia was completely absent in V1AR knock-out mice. In wild-type mice, OXT-induced analgesia could be fully prevented by pretreatment with a V1AR but not an OTR antagonist. Receptor binding studies demonstrated that the distribution of OXT and AVP binding sites in mouse lumbar spinal cord resembles the pattern observed in rat. AVP binding sites diffusely label the lumbar spinal cord, whereas OXT binding sites cluster in the substantia gelatinosa of the dorsal horn. In contrast, quantitative real-time reverse transcription (RT)-PCR revealed that V1AR but not OTR mRNA is abundantly expressed in mouse dorsal root ganglia, where it localizes to small- and medium-diameter cells as shown by single-cell RT-PCR. Hence, V1ARs expressed in dorsal root ganglia might represent a previously unrecognized target for the analgesic action of OXT and AVP.
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PMID:Oxytocin-induced analgesia and scratching are mediated by the vasopressin-1A receptor in the mouse. 2055 79

Recent research indicates that the neuropeptide oxytocin and the gene for the oxytocin receptor (OXTR) have been implicated in the modulation of various social behaviors, including those related to empathy and sensitivity to others. In this study, we examine the hypothesis that genetic variation in OXTR is associated with autonomic reactions when perceiving others in distress. We also explore the possibility that individual disposition in empathic concern would differ by OXTR genotype. To address these questions, 51 male participants (18-35 years of age), genotyped for OXTR rs53576, viewed a social interaction containing high levels of individual distress and apparent physical pain. Electrodermal activity, a measure of sympathetic nervous system activity, was collected during the presentation of the stimuli. Participants also completed a self-report dispositional measure of empathy prior to starting the study and provided ratings of arousal while viewing the stimuli. OXTR variant rs53576 GG individuals showed increased levels of sympathetic and subjective arousal in response to the stimuli compared to A allele carriers. GG homozygotes also expressed greater levels of empathic concern. These findings support the importance of the oxytocin receptor variation in emotional and physiological reactions to the affective experiences of other conspecifics.
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PMID:Oxytocin receptor gene variation predicts empathic concern and autonomic arousal while perceiving harm to others. 2429 35

We have previously reported that induction of adenomyosis in mice results in progressive hyperalgesia, uterine hyperactivity, and elevated plasma corticosterone levels and that epigallocatechin-3-gallate (EGCG) treatment dose dependently suppressed myometrial infiltration and improved generalized hyperalgesia. In this study, we examined whether adenomyosis induced in mice results in the loss of GABAergic inhibition as manifested by the diminished glutamate decarboxylase (GAD) 65-expressing neurons in the brainstem nucleus raphe magnus (NRM) that could correlate with heightened hyperalgesia. We also evaluated whether EGCG treatment would reverse these changes and also improve the expression of some proteins known to be involved in adenomyosis. Adenomyosis was induced in 28 female ICR mice and additional 12 were used as blank controls, as reported previously. At the 16th week, all mice with induced adenomyosis received low- or high-dose EGCG treatment or untreated. Mice without adenomyosis received no treatment. After 3 weeks of treatment, their uterine horns and brains were harvested. The right uterine horn was used for immunohistochemistry analysis and for counting the number of macrophages infiltrating into the ectopic endometrium. The brainstem NRM sections were subjected to immunofluorescence staining for GAD65. We found that mice with induced adenomyosis had significantly diminished GAD65-expressing neurons, concomitant with heightened hyperalgesia. Treatment with EGCG increased these neurons in conjunction with improved hyperalgesia, reduced the expression of p-p65, cycloxygenase 2, oxytocin receptor, collagen I and IV, and transient receptor potential vanilloid type 1 in ectopic endometrium or myometrium, reduced the number of macrophages infiltrating into the ectopic endometrium while elevated the expression of progesterone receptor isoform B. Thus, adenomyosis-induced pain resembles neuropathic pain in that there is a remarkable central plasticity.
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PMID:Possible Loss of GABAergic Inhibition in Mice With Induced Adenomyosis and Treatment With Epigallocatechin-3-Gallate Attenuates the Loss With Improved Hyperalgesia. 2449 88

The treatment of chronic pain arising from deep tissues is currently inadequate and there is need for new pharmacological agents to provide analgesia. The endogenous paracrine hormone/neurotransmitter oxytocin is intimately involved in the modulation of multiple physiological and psychological functions. Recent experiments have given clear evidence for a role of oxytocin in the modulation of nociception. The present article reviews the existent human and basic science data related to the direct and indirect effects of oxytocin on pain. Due to its analgesic, anxiolytic, antidepressant and other central nervous system effects, there is strong evidence that oxytocin and other drugs acting through the oxytocin receptor could act as multifunctional analgesics with unique therapeutic value.
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PMID:Oxytocin - a multifunctional analgesic for chronic deep tissue pain. 2534 12

The neuromodulators oxytocin and serotonin have been implicated in regulating affective processes underlying empathy. Understanding this dependency, however, has been limited by a lack of objective metrics for measuring empathic performance. Here we employ a novel psychophysical method for measuring empathic performance that quantitatively measures the ability of subjects to decode the experience of another person's pain. In 50 female subjects, we acquired functional magnetic resonance imaging data as they were exposed to a target subject experiencing variable degrees of pain, whilst performing an irrelevant attention-demanding task. We investigated the effect of variation in the oxytocin receptor gene (OXTR) and the serotonin transporter gene (SLC6A4) on the psychophysical and neurometric variability associated with empathic performance. The OXTR rs2268498 and rs53576 polymorphisms, but not the SLC6A4 5-HTTLPR, were associated with significant differences in empathic accuracy, with CC- and AA-carriers, respectively, displaying higher empathic accuracy. For OXTR rs2268498 there was also a genotype difference in the correlation between empathic accuracy and activity in the superior temporal sulcus (STS). In OXTR rs2268498 CC-carriers, high empathic accuracy was associated with stronger responsiveness of the right STS to the observed pain. Together, the results show that genetic variation in the OXTR has significant influence on empathic accuracy and that this may be linked to variable responsivity of the STS.
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PMID:Variation in the oxytocin receptor gene is associated with behavioral and neural correlates of empathic accuracy. 2553 88

Oxytocin (OT) plays an important role in pain modulation and antinociception in the central nervous system. However, little is known about its peripheral effects. This study was conducted to investigate the effect of OT on the electrical properties of neurons in the dorsal root ganglia (DRG) and the underlying mechanisms. DRG neurons from adult rats were acutely dissociated and cultured. Intracellular Ca(2+) was determined by fluorescent microscopy using an indicator dye. The electrical properties of DRG neurons were tested by patch-clamp recording. The oxytocin receptor (OTR) and neuronal nitric oxide synthase (nNOS) on DRG neurons were assessed with immunofluorescence assays. OTR co-localized with nNOS in most of Isolectin B4 (IB4)-binding cultured DRG neurons in rats. OT decreased the excitability, increased the outward current, and evoked the membrane hyperpolarization in cultured DRG neurons. Sodium nitroprusside (SNP), the donor of nitric oxide (NO), exerted similar effects as OT on the membrane potential of cultured DRG neurons. OT increased the production of NO in DRGs and cultured DRG neurons. Pre-treatment of the OTR antagonist atosiban or the selective nNOS inhibitor N-Propyl-l-arginine (NPLA) significantly attenuated the hyperpolarization effect evoked by OT. OT produced a concentration-dependent increase in intracellular Ca(2+) in DRG neurons that responds to capsaicin, which can be attenuated by atosiban, but not by NPLA. OT-evoked membrane hyperpolarization and increase of outward current were distinctly attenuated by glibenclamide, a blocker of ATP-sensitive K(+) (KATP) channel. OT might be an endogenous antinociceptive agent and the peripheral antinociceptive effects of OT are mediated by activation of the Ca(2+)/nNOS/NO/KATP pathway in DRG neurons.
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PMID:Oxytocin-induced membrane hyperpolarization in pain-sensitive dorsal root ganglia neurons mediated by Ca(2+)/nNOS/NO/KATP pathway. 2561 53

The human brain responds more strongly to racial ingroup than outgroup individuals' pain. This racial ingroup bias varies across individuals and has been attributed to social experiences. What remains unknown is whether the racial ingroup bias in brain activity is associated with a genetic polymorphism. We investigated genetic associations of racial ingroup bias in the brain activity to racial ingroup and outgroup faces that received painful or non-painful stimulations by scanning A/A and G/G homozygous of the oxytocin receptor gene polymorphism (OXTR rs53576) using functional MRI. We found that G/G compared to A/A individuals showed stronger activity in the anterior cingulate and supplementary motor area (ACC/SMA) in response to racial ingroup members' pain, whereas A/A relative to G/G individuals exhibited greater activity in the nucleus accumbens (NAcc) in response to racial outgroup members' pain. Moreover, the racial ingroup bias in ACC/SMA activity positively predicted participants' racial ingroup bias in implicit attitudes and NAcc activity to racial outgroup individuals' pain negatively predicted participants' motivations to reduce racial outgroup members' pain. Our results suggest that the two variants of OXTR rs53576 are associated with racial ingroup bias in brain activities that are linked to implicit attitude and altruistic motivation, respectively.
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PMID:Oxytocin receptor gene and racial ingroup bias in empathy-related brain activity. 2563 90


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