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Why is running a marathon like giving birth? The possible role of oxytocin in the underestimation of the memory of pain induced by labor and intense exercise

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Abstract

Pain can be overestimated, underestimated or reported accurately at recall. The way pain is remembered seems to depend on certain factors, including the type of pain or, in other words, its cause, the context, and the meaning it has for the person suffering from it. For instance, episodes of chronic pain, as well as pain related to surgery, are often overestimated at recall. Interestingly, research shows that pain induced by parturition or marathon running is often underestimated at recall despite the fact that both are not only physically grueling but also emotionally intense experiences. However, both processes can likewise be considered positive events, as opposed to most that involve pain. On the neurophysiological level, one of the similarities between giving birth and running a marathon is the particular involvement of the oxytocin system. Oxytocin is involved both in parturition and intense exercise, for various reasons. During labor, oxytocin mediates uterine contractions, while in the case of extensive running it might be involved in the maintenance of fluid balance. It also has well-documented analgesic properties and plays an important role in memory formation and recall. It has been suggested that oxytocin modulates the output of the central nucleus of the amygdala (CeA)during the fear recall. Moreover, it has been demonstrated that oxytocin can impair fear learning and influence the memory of both positive and negative emotionally salient stimuli. We propose that the reason for pain to be remembered in a more favorable light is the central action of oxytocin in the central nucleus of the amygdala, first and foremost during the encoding phase.

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... This analogy is relevant because euphoria levels are significantly increased after running (Boecker et al., 2008), and runner's high is one of the paradigmatic cases of ASC that is due principally to a transient state of hypofrontality (Dietrich & Al-Shawaf, 2018). According to Farley et al. (2019), labor pain and marathon pain share not only positive emotional valence but also physiological mechanisms. Both physiological childbirth and extreme physical exertion involve a number of endogenous systems and substances that are specific to these two types of experiences, including endocannabinoids and endogenous opioids, and the oxytocin system, which is related to analgesia and memory. ...
... It has been demonstrated that oxytocin can impair fear acquisition and influence the memory of both positive and negative emotionally salient stimuli. Farley et al. (2019) hypothesized that, primarily during the encoding phase, oxytocin influences memory of pain through its inhibiting action in the central nucleus of the amygdala during the painful event, (i.e., during memory formation). Note, however, that Farley et al. (2019) did not connect the oxytocin system mechanism to hypofrontality. ...
... Farley et al. (2019) hypothesized that, primarily during the encoding phase, oxytocin influences memory of pain through its inhibiting action in the central nucleus of the amygdala during the painful event, (i.e., during memory formation). Note, however, that Farley et al. (2019) did not connect the oxytocin system mechanism to hypofrontality. Further research in this direction may shed light on the biochemical aspects of transient hypofrontality. ...
Article
In this article, I present the concept of “birthing consciousness,” a psychophysical altered state of women that can occur during natural and undisturbed birth. I demonstrate that this altered state of consciousness (ASC) has phenomenological and cognitive features of hypofrontality; thus, birthing consciousness probably shares a similar brain mechanism to that postulated by the transient-hypofrontality theory (THT). I argue that until recently (with the advent of modern medical intervention), in evolutionary terms, women lacking the proclivity for this specific brain mechanism had a lower chance of reproducing successfully. Hence, I suggest a general and preliminary hypothesis concerning THT: Birthing consciousness is one example of an adaptive pain-induced ASC associated with transient hypofrontality.
... 3,5,8,11,14,15,20,[23][24][25][26][27][28][29] These studies mostly emphasize the role of negative affect, 5,11,14,15,20,[23][24][25][26]28 whereas some recent studies suggest that positive affect may also be of importance, especially in terms of pain associated with positively valued experiences. 3,30 One previous study shows that negative affect experienced after reaching the marathon finish line enabled pain memory predictions. The influence of positive affect on pain memory was statistically nonsignificant, but a trend was revealed, suggesting the need for further research. ...
... It is hypothesized that oxytocin can inhibit the action of the central nucleus of the amygdala (CeA), which is involved in memory consolidation. 30 It has also been found that post-training administration of sub-analgesic doses of beta-endorphin causes retrograde amnesia. 53 In the light of these data, the question arises of whether participants' memory of pain induced by physical exercise was distorted or rather participants did not have enough opportunity to encode and consolidate their pain-related experiences. ...
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Background: Memory and in turn, memory of pain is a reconstructive process. This study considers the relationship between time, memory, affective states, and pain induced by running a marathon by investigating the influence of these factors on a participant's memory of pain experienced after a marathon. The following two hypotheses were formulated: 1) participants' recalled-pain of marathon experience is underestimated; and 2) the underestimation of recalled pain would be greater for participants experiencing higher positive affect. Methods: A longitudinal design was employed to check pain intensities of marathon participants a) at the finish line and b) 6 months following its completion. The sample size was based on a power analysis, and 108 marathonists rated their pain intensities and positive and negative affects at the finish line. From this sample, 58 participants recalled their pain experience of running the marathon 6 months later. Linear models, including computer-based data-mining algorithms, were used. Results: The experienced pain was higher than their recalled pain (t(55) = 3.412, p < 0.01, d = 0.45), supporting the first hypothesis. The memory of pain faded similarly in all participants, which did not directly support the second hypothesis. Further exploratory analysis suggested that negative and positive affective states were related to participants' pain memory; positive affective states appeared to be inversely related to the recall (β = -0.289, p = 0.039). Discussion: This study shows that time has a significant effect on memory recall and that emotions may also influence the memory of pain. This is the first study that preliminarily showcased the effect of positive affective states on the memory of pain induced by physical exercise.
... [27][28][29][30] Running a marathon, like giving birth, might increase the concentration of beta-endorphins and oxytocin, which in turn impair memory of negative aspects of such experiences, eg, pain. 31 The current study suggests that the experience and the memory of pain induced by physical effort may change as a result of cognitive factors. The expected intensity of upcoming pain determined the way it was felt. ...
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Purpose: It has been shown that the memory of pain induced by running might be underestimated. Our previous study showed the contribution of emotional factors to this process. This study aimed to investigate the cognitive factors that might influence the memory of this type of pain, ie expectancy of pain intensity, expectancy of pain unpleasantness, and desire for pain relief. Participants and methods: A total of 49 half-marathon runners rated the intensity and unpleasantness of pain immediately after completing a run and one month later. Participants rated the expected intensity and unpleasantness of the upcoming pain before starting the run, as well as the desire for pain relief after its completion. Those who also participated in the previous edition of the half marathon were asked to recall the pain experienced due to that run. Results: Participants underestimated remembered pain intensity and unpleasantness. The desire for pain relief mediated the memory of pain intensity (p < 0.05), while expectancy of pain intensity influenced memory of pain intensity (a × b) through its effect on the experienced pain (bootstrapped point estimate = 0.08; 95% CI: 0.02-0.32). The remembered intensity of pain experienced during the previous half marathon affected the current pain experience directly (p < 0.05) or indirectly (a × b) by generating pain-related expectancy (bootstrapped point estimate = 0.11; 95% CI: 0.01-0.46). The cognitive variables did not influence the memory of pain unpleasantness. Conclusion: The memory of pain induced by sports activity may change due to cognitive factors; however, further research is needed to investigate their role in shaping the memory of the sensory and affective dimensions of pain.
... This natural process may be a causal factor of the postpartum occurrence of 'the superwoman syndrome,' a woman's feeling immediately after an undisturbed physiological birth that she can do anything, as if she has super powers (Cheyney, 2011;Kurz et al., 2019). 2 In fact, labor pain exhibits positive emotional valence during which the level of euphoria is significantly increased. Both natural birth and extreme physical effort, such as running a marathon, involve endocannabinoids, opioids, and oxytocinall related to pain relief (Farley et al., 2019). ...
Article
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Birthing consciousness" is a psycho-physical state of focus and retreat into which a woman sometimes enters during physiological birth. When this state is initiated and continues uninterrupted, the probability of a natural birthing process increases. Adversely, interruptions to the state of birthing consciousness slow down or even stop the birth from progressing. In this theoretical examination, I claim that birthing consciousness was a useful adaptation in human evolutionary time. However, in current hospital settings there are various interruptions to birthing consciousness. I offer a critical insight: obstetrics has neglected to exploit evolutionary advantages. Moreover, attention to evolutionary adaptation in the hospital generally, or obstetrics specifically, will advance best medical practices, thus public health in general. The suggested evolutionary approach offers a new perspective concerning the cascade of interventions in the birth process. It also suggests a path for future research concerning the reduction in the rate of unscheduled cesarean births, on the rise in current obstetrical care.
... In this situation, submitting to pain feels quite good (see also Dahan, 2019). Both physiological birth and extreme physical effort, such as marathon runs, involve several similar endogenous opioids, including endocannabinoids and oxytocin, which was found to be related to analgesia and memory (Farley, Piszczek, & Bąbel, 2019). ...
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This paper focuses on the riddle of the extreme ends of the birth experience. On one end, are women who experience relatively successful childbirth as traumatic, and suffer from poor mental health during postpartum, varying from baby blues to postpartum depression and up to childbirth-related PP-PTSD. On the other, are women who experience childbirth as a highly positive, life-altering event. I offer that both extremes can be understood from the phenomenon of birthing consciousness and its fragility. When natural birth is uninterrupted, there are more chances for a natural birth process. At the end of an undisturbed natural delivery, women report ‘natural high’ sensations. However, even minor physical and environmental interruptions to the birthing woman stop the birth from progressing, thus requiring medical interventions. Out of analyzing the psycho-physical states during birth – natural and undisturbed versus highly medicated births – I claim that the fragility of birthing consciousness is the answer to the riddle of the extreme ends of the birth experience. Thus, the question ‘how does a low-risk woman get to a highly medicated birth?’ should be answered, not only in a physiological orientation, but also in a psycho-physiological and environmental context. Typical modern hospital birth environments often interrupt birthing consciousness, leading to a cascade of medical interventions and highly medicalized births with extremely negative birth experiences, which often results in poor mental health in postpartum. I argue that the first step to support a woman during a physiological birth, is to acknowledge the particular psycho-physical state of the birthing woman and its fragility, and not interrupt it unnecessarily.
... Future longitudinal studies could follow the course of identity fusion as well as event-related mechanisms of fusion over the antenatal and postpartum periods. It would also be interesting to measure other mechanisms of pain perception and epidural use [e.g., 60], endogenous oxytocin levels and exposure to synthetic oxytocin such as Pitocin [e.g., 61,62], and stress hormone levels such as cortisol [e.g., 63] at different time points before, during, and after childbirth. Our sample is not representative of first-time mothers outside the United States; future analyses could explore possible cultural differences across Western and non-Western cultures. ...
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Oxytocin is a hypothalamic neuropeptide first recognized as a regulator of parturition and lactation which has recently gained attention for its ability to modulate social behaviors. In this chapter, we review several aspects of the oxytocinergic system, focusing on evidence for release of oxytocin and its receptor distribution in the cortex as the foundation for important networks that control social behavior. We examine the developmental timeline of the cortical oxytocin system as demonstrated by RNA, autoradiographic binding, and protein immunohistochemical studies, and describe how that might shape brain development and behavior. Many recent studies have implicated oxytocin in cognitive processes such as processing of sensory stimuli, social recognition, social memory, and fear. We review these studies and discuss the function of oxytocin in the young and adult cortex as a neuromodulator of central synaptic transmission and mediator of plasticity.
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Background The majority of women experience pain during labour and childbirth, however not all women experience it in the same way. In order to develop a more complete understanding of labour pain, this study aimed to examine women’s experiences within the perspective of modern pain science. A more complete understanding of this phenomenon can then guide the development of interventions to enhance women’s experiences and potentially reduce their need for pharmacological intervention. Methods A qualitative study was conducted using phenomenology as the theoretical framework. Data were collected from 21 nulliparous women, birthing at one of two large maternity services, through face-to-face interviews and written questionnaires. Data were analysed using an Interpretative Phenomenological Analysis approach. Results The data from this study suggest that a determining factor of a woman’s experience of pain during labour is the meaning she ascribes to it. When women interpret the pain as productive and purposeful, it is associated with positive cognitions and emotions, and they are more likely to feel they can cope. Alternatively, when women interpret the pain as threatening, it is associated with negative cognitions and emotions and they tend to feel they need help from external methods of pain control. The social environment seems particularly important in shaping a woman’s pain experience by influencing her interpretation of the context of the pain, and in doing so can change its meaning. The context and social environment are dynamic and can also change throughout labour. Conclusion A determining factor in a woman’s experience of pain during labour is its perceived meaning which can then influence how the woman responds to the pain. The meaning of the pain is shaped by the social environment and other contextual factors within which it is experienced. Focussed promotion of labour pain as a productive and purposeful pain and efforts to empower women to utilise their inner capacity to cope, as well as careful attention to women’s cognitions and the social environment around them may improve women’s experiences of labour pain and decrease their need for pain interventions. Electronic supplementary material The online version of this article (doi:10.1186/s12884-017-1343-3) contains supplementary material, which is available to authorized users.
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Objective: This study assessed changes in anxiety during different phases of childbirth in a sample of women demanding epidural anesthesia. Design: Prospective, longitudinal case series. Sample: A total of 133 women who demanded epidural anesthesia for childbirth answered the questionnaires. Methods: Anxiety state was measured using the State Trait Anxiety Inventory (STAI) questionnaire. The STAI-S (anxiety state) was administered in three phases during childbirth: Phase 1 was before applying epidural anesthesia, Phase 2 was 45 min after the application of epidural anesthesia and Phase 3 was at less than 24 h after delivery. Data were collected in two general hospitals: a third-level public hospital and a well-recognized private hospital. Main outcome measures: STAI scores. Results: Anxiety state decreases significantly after applying the epidural anesthesia (Phase 2) compared to before anesthesia (Phase 1), and it remains low levels 24 h after childbirth (Phase 3). There were statistically significant differences in STAI scores between the different phases administrated (Phases 1 and 2: p < 0.001; effect size, d = 1.40; Phases 1 and 3: p < 0.001; effect size, d = 1.39). In Phase 3, women with cesarean section birth had significant differences in STAI scores relative to those with spontaneous birth (p = 0.037; d = 0.44). The type of health-care setting (public or private), the educational level and the numbers of previous births does not affect the level of anxiety state in women in any of the three phases. Conclusions: Women’s anxiety decreases significantly after applying epidural anesthesia, and it remains low 24 h after delivery. Anxiety against childbirth was not influenced by the health system used by women, by the condition of primiparous or multiparous, or by the educational level. Women who received an epidural anesthesia with a cesarean section reported higher rates of anxiety state after birth.
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Background. Validity of pain recall is questioned in research.Objective.To evaluate the reliability of pain intensity recall for seniors in an emergency department (ED).Methods.This study was part of a prospective multicenter project for seniors (≥65 years old) treated in an ED for minor traumatic injury. Pain intensity (0-10 numerical rating scale) was evaluated at the initial ED visit, at one week (baseline), and 3 months. At three months, patients were asked to recall the pain intensity they had at baseline.Results.482 patients were interviewed (mean age 76.6 years, SD ± 7.3) and 72.8% were female. Intraclass correlation coefficient between pain at baseline and its recall was 0.24 (95% CI: 0.14-0.33). Senior patients tended to overestimate their pain intensity by a mean of 1.2 (95% CI: 0.9-1.5) units. A stepwise multiple regression analysis showed that the variance of baseline pain recall at 3 months was explained by pain at ED visit (11%), pain at 3 months (7%), and pain at baseline (2%).Conclusion.The accuracy of pain intensity recall after three months is poor in seniors and seems to be influenced by the pain experienced at the time of injury.
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Early-life sensory input plays a crucial role in brain development. Although deprivation of orofacial sensory input at perinatal stages disrupts the establishment of the barrel cortex and relevant callosal connections, its long-term effect on adult behavior remains elusive. In this study, we investigated the behavioral phenotypes in adult mice with unilateral transection of the infraorbital nerve (ION) at postnatal day 3 (P3). Although ION-transected mice had normal locomotor activity, motor coordination, olfaction, anxiety-like behaviors, novel object memory, preference for social novelty and sociability, they presented deficits in social memory and spatial memory compared with control mice. In addition, the social memory deficit was associated with reduced oxytocin (OXT) levels in the hypothalamus and could be partially restored by intranasal administration of OXT. Thus, early sensory deprivation does result in behavioral alterations in mice, some of which may be associated with the disruption of oxytocin signaling. Electronic supplementary material The online version of this article (doi:10.1186/s13041-016-0278-3) contains supplementary material, which is available to authorized users.
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Background: Patient-reported outcome measures (PROMs) are valuable tools for quantifying outcomes of orthopedic surgery. However, when baseline scores are not obtained, there is considerable controversy about whether PROMs can be administered retrospectively for patients to recall their preoperative state. We investigated the accuracy of patient recall after total shoulder arthroplasty (TSA) using the American Shoulder and Elbow Surgeons (ASES) assessment score. Methods: Recalled ASES scores were collected postoperatively at 6 weeks, 3 months, 6 months, and 12 months from 169 patients who previously completed baseline scores before TSA. The ASES total score was divided into its two subcomponents: functional ability and visual analog scale (VAS) for pain. We compared preoperative and recalled scores for each subcomponent and the total ASES score. Results: Recalled ASES function scores were comparable to corresponding preoperative scores across all time points (analysis of variance, P = .21), but recalled VAS pain was significantly higher at all time points beyond 6 weeks after surgery (P = .0001 at 3 months; P = .005 at 6 months; and P = .001 at 12 months). As a result, the ASES total score was only comparable at 6 weeks after surgery (P = .39) and differed at all time points thereafter. Conclusion: Patients are able to recall preoperative function with considerable accuracy for up to 12 months after TSA. However, beyond 6 weeks postoperatively, patients recall having worse pain than they originally reported, and recalled ASES total scores are unreliable as a result.
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Background: Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. Methods: Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. Results: Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. Conclusions: The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits.
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The aims of the study were to assess the memory of dental pain induced by tooth restoration and to investigate the factors that influence the memory of pain. Two dimensions of pain, i.e., pain intensity and pain unpleasantness, were measured twice: immediately after dental treatment and at 6 or 12 weeks follow up. Regardless of the length of the recall delay, mean pain was recalled accurately, but mean pain unpleasantness was underestimated. However, underestimation of pain intensity and unpleasantness at the follow-up was observed only in the subjects who reported more intense and unpleasant pain immediately after dental treatment. Moreover, those who underestimated pain intensity and/or unpleasantness had higher scores on dental anxiety and reported more state anxiety and less positive affect before dental treatment.
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Anxiety sensitivity, a trait characterised by fear of anxiety-related body sensations, has been linked to heightened attention to pain, appraising body sensations as threatening, and remembering threat-related information. We assessed whether individuals with greater anxiety sensitivity overestimate in remembering pain. We also assessed whether emotion regulation strategies that direct attention away from pain (distraction), or alter appraisals of pain (reappraisal), alleviate memory bias. Participants (N = 137) were randomly assigned to one of two emotion regulation conditions or to a control condition before taking part in a cold pressor task. Greater anxiety sensitivity was associated with overestimation in remembering pain. Engaging in reappraisal mitigated this memory bias but engaging in distraction did not. This is the first study to examine the relations among anxiety sensitivity, emotion regulation and memory for pain. The findings suggest that health-care practitioners can encourage reappraisal to promote more positive memories of procedural pain, particularly in patients high in anxiety sensitivity.
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The present study investigated how oxytocin (OT) signaling in the central (CeA) and basolateral (BLA) amygdala affects acquisition, expression, and extinction of context-conditioned fear (freezing) in rats. In the first set of experiments, acquisition of fear to a shocked context was impaired by a preconditioning infusion of synthetic OT into the CeA (Experiment 1) or BLA (Experiment 2). In the second set of experiments, expression of context fear was enhanced by a pre- or post-extinction CeA infusion of synthetic OT (Experiments 3-6) or a selective OT receptor agonist, TGOT (Experiment 4). This enhancement of fear was blocked by coadministration of an OT receptor antagonist, OTA (Experiment 5) and context fear was suppressed by administration of the antagonist alone (Experiment 6). In the third set of experiments, expression of context fear was suppressed, not enhanced, by a preextinction BLA infusion of synthetic OT or a selective OT receptor agonist, TGOT (Experiments 7 and 8). This suppression of fear was blocked by coadministration of the OT receptor antagonist, OTA (Experiment 8). Taken together, these findings show that the involvement of the CeA and BLA in expression and extinction of context-conditioned fear is dissociable, and imply a critical role for oxytocin signaling in amygdala-based regulation of aversive learning. © 2015 Campbell-Smith et al.; Published by Cold Spring Harbor Laboratory Press.
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The aim of this study was to assess the memory of pain induced by running a marathon and the factors that influence it. Sixty-two marathon runners participated in the study, which comprised two phases. Immediately after a participant had reached the finishing line of the marathon, they were asked to rate the intensity and the unpleasantness of their pain and the emotions they felt at that time. Either three or six months later they were asked again to rate the intensity and the unpleasantness of the same pain experience. Regardless of the length of recall delay, participants underestimated both recalled pain intensity and unpleasantness. The pain and negative affect reported at the time of the pain experience accounted for 24% of the total variance in predicting recalled pain intensity and 22% of the total variance in predicting recalled pain unpleasantness. Positive affect at the time of pain experience was not a significant predictor of both the recalled pain intensity and pain unpleasantness. It is concluded that pain induced by physical exercise is not remembered accurately and the pain and negative affect experienced influence recall. Further research is needed on the influence of positive affect on the memory of pain.
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Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory of emotionally arousing experiences. However, as the onset of these glucocorticoid actions appear often too rapid to be explained by genomic regulation, the neurobiological mechanism of how glucocorticoids could modify the memory-enhancing properties of norepinephrine and CRF remained elusive. Here, we show that the endocannabinoid system, a rapidly activated retrograde messenger system, is a primary route mediating the actions of glucocorticoids, via a glucocorticoid receptor on the cell surface, on BLA neural plasticity and memory consolidation. Furthermore, glucocorticoids recruit downstream endocannabinoid activity within the BLA to interact with both the norepinephrine and CRF systems in enhancing memory consolidation. These findings have important implications for understanding the fine-tuned crosstalk between multiple stress hormone systems in the coordination of (mal)adaptive stress and emotional arousal effects on neural plasticity and memory consolidation.Neuropsychopharmacology accepted article preview online, 30 December 2014. doi:10.1038/npp.2014.334.
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Background: Current neurocircuitry models of anxiety disorders posit a lack of inhibitory tone in the amygdala during acquisition of Pavlovian fear responses and deficient encoding of extinction responses in amygdala-medial prefrontal cortex circuits. Competition between these two responses often results in a return of fear, limiting control over anxiety. However, one hypothesis holds that a pharmacologic strategy aimed at reducing amygdala activity while simultaneously augmenting medial prefrontal cortex function could facilitate the extinction of conditioned fear. Methods: Key among the endogenous inhibitors of amygdala activity in response to social fear signals is the hypothalamic peptide oxytocin. To address the question whether oxytocin can strengthen Pavlovian extinction beyond its role in controlling social fear, we conducted a functional magnetic resonance imaging experiment with 62 healthy male participants in a randomized, double-blind, parallel-group, placebo-controlled design. Specifically, subjects were exposed to a Pavlovian fear conditioning paradigm before receiving an intranasal dose (24 IU) of synthetic oxytocin or placebo. Results: Oxytocin, when administered intranasally after Pavlovian fear conditioning, was found to increase electrodermal responses and prefrontal cortex signals to conditioned fear in the early phase of extinction and to enhance the decline of skin conductance responses in the late phase of extinction. Oxytocin also evoked an unspecific inhibition of amygdalar responses in both phases. Conclusions: Collectively, our findings identify oxytocin as a differentially acting modulator of neural hubs involved in Pavlovian extinction. This specific profile of oxytocin action may open up new avenues for enhancing extinction-based therapies for anxiety disorders.
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Social recognition, the ability to recognize individuals that were previously encountered, requires complex integration of sensory inputs with previous experience. Here, we use a variety of approaches to discern how oxytocin-sensitive neurons in the PFC exert descending control over a circuit mediating social recognition in mice. Using male mice with Cre-recombinase directed to the oxytocin receptor gene (Oxtr), we revealed that oxytocin receptors (OXTRs) are expressed on glutamatergic neurons in the PFC, optogenetic stimulation of which elicited activation of neurons residing in several mesolimbic brain structures. Optogenetic stimulation of axons in the BLA arising from OXTR-expressing neurons in the PFC eliminated the ability to distinguish novel from familiar conspecifics, but remarkably, distinguishing between novel and familiar objects was unaffected. These results suggest that an oxytocin-sensitive PFC to BLA circuit is required for social recognition. The implication is that impaired social memory may manifest from dysregulation of this circuit.SIGNIFICANCE STATEMENT Using mice, we demonstrate that optogenetic activation of the neurons in the PFC that express the oxytocin receptor gene (Oxtr) impairs the ability to distinguish between novel and familiar conspecifics, but the ability to distinguish between novel and familiar objects remains intact. Subjects with autism spectrum disorders (ASDs) have difficulty identifying a person based on remembering facial features; however, ASDs and typical subjects perform similarly when remembering objects. In subjects with ASD, viewing the same face increases neural activity in the PFC, which may be analogous to the optogenetic excitation of oxytocin receptor (OXTR) expressing neurons in the PFC that impairs social recognition in mice. The implication is that overactivation of OXTR-expressing neurons in the PFC may contribute to ASD symptomology.
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Current models suggest that neuropeptide oxytocin modulates the salience of emotional/social stimuli and consequently influences perceptual, attentional and learning processes that underlie social behaviour. Therefore, oxytocin has been considered as a potential treatment in managing social and communication deficits in neuropsychological disorders. Recent studies indicate that effects of oxytocin on social and cognitive functions greatly vary and even lead to opposite outcomes. The factors leading to such variabilities in behavioural effects of oxytocin and their underlying mechanisms remain unclear. Here, we examined the effects of exogenously administered (intranasal) oxytocin (48 IU) on cognitive functions of macaque monkeys within a controlled experimental condition in a randomized crossover study. Monkeys performed a working memory task in which they memorized and subsequently matched stimuli with different emotional/social content (positive, negative, and neutral) at different levels of cognitive difficulties (delay period). Monkeys’ accuracy was lower at longer delay intervals indicating that higher cognitive demands adversely affected their performance. There was a significant difference in accuracy and response time between the three emotional conditions. The effects of oxytocin on monkeys’ performance were dependent on the emotional content of stimuli so that oxytocin enhanced the adverse effects of negative stimuli, however, moderated the effects of positive stimuli. Our findings in monkeys do not support models suggesting a general effect of oxytocin in enhancing salience or heightening of attention to social stimuli and instead suggest that the cognitive effects of oxytocin depend on the emotional valence of contextual factors.
Article
Background: The pain experience associated with labour is complex. Literature indicates psychosocial and environmental determinants of labour pain, and yet methods to support women usually target physiological attributes via pharmacological interventions. Aim: To provide an update of our understanding of labour pain based on modern pain science. The review aims to help explain why women can experience labour pain so differently - why some cope well, whilst others experience great suffering. This understanding is pertinent to providing optimal support to women in labour. Method: A literature search was conducted in databases Medline, Cumulative Index to Nursing and Allied Health Literature and PsycINFO, using search terms labor/labour, childbirth, pain, experience and perception. Thirty-one papers were selected for inclusion. Findings: Labour pain is a highly individual experience. It is a challenging, emotional and meaningful pain and is very different from other types of pain. Key determinants and influences of labour pain were identified and grouped into cognitive, social and environmental factors. Conclusion: If a woman can sustain the belief that her pain is purposeful (i.e. her body working to birth her baby), if she interprets her pain as productive (i.e. taking her through a process to a desired goal) and the birthing environment is safe and supportive, it would be expected she would experience the pain as a non-threatening, transformative life event. Changing the conceptualisation of labour pain to a purposeful and productive pain may be one step to improving women's experiences of it, and reducing their need for pain interventions.
Article
Free access to the article for the first 50 days: https://authors.elsevier.com/c/1WgGj3Q9h1uvTc The central nucleus of the amygdala (CEA) is a striatum-like structure orchestrating a diverse set of adaptive behaviors, including defensive and appetitive responses. Studies using anatomical, electrophysiological, imaging and optogenetic approaches revealed that the CEA network consists of recurrent inhibitory circuits comprised of precisely connected functionally and genetically defined cell types that can select and control specific behavioral outputs. While bivalent functionality of the CEA in adaptive behavior has been clearly demonstrated, we are just beginning to understand to which degree individual CEA circuit elements are functionally segregated or overlapping. Importantly, recent studies seem to suggest that optogenetic manipulations of the same, or overlapping cell populations can give rise to distinct, or sometimes even opposite, behavioral phenotypes. In this review, we discuss recent progress in our understanding of how defined CEA circuits can control defensive and appetitive behaviors, and how seemingly contradictory results could point to an integrated concept of CEA function.
Article
Background: A previous study has shown that memory of pain induced by running a marathon might be underestimated. However, little is known about the factors that might influence such a memory distortion during pain recall. The aim of the study was to investigate the memory of pain induced by running a marathon and the factors that might influence it: (1) present pain during recall and (2) recall delay. Methods: A total of 127 marathon runners participated in the study, which comprised of two phases. After completion of the marathon, participants were asked to rate the intensity and the unpleasantness of their pain. Either a week or a month later, they were asked again to rate the intensity and the unpleasantness of the remembered and present pain experience. Results: Participants underestimated remembered pain intensity and pain unpleasantness only if they did not experience pain during recall (p < 0.05). We observed a trend for underestimation after a week (p = 0.09) and significant effect after a month (p < 0.05) of recall delay. Furthermore, present pain intensity during recall significantly mediated the memory of pain intensity induced by running the marathon, but only after a month. Similarly, present pain unpleasantness during recall significantly mediated the memory of pain unpleasantness, but only after a month. Conclusions: It is concluded that memory of pain induced by running the marathon is underestimated after a month of recall delay and mediated by present pain during recall. Significance: This study explores factors acting during recall, influencing memory of naturally occurring pain induced by physical effort. The empirical findings provide the first robust evidence for a causal relationship between memory of pain and present pain during recall.
Article
Objectives: Previous research on pain memory provides inconsistent evidence about the accuracy of pain recall, and few studies have attempted to examine broad affective and contextual contributions to this phenomenon. The present research aimed to determine the accuracy of postoperative pain recall after a 3-months, with respect to the context of the surgery and the congruence of affective states concurrent with the initial experience and its recall. The study also aimed to identify predictors of remembered pain by analysing a range of sensory, cognitive and affective factors. Methods: Older adults, undergoing planned (N=40) and unplanned hip surgery (N=31), were enrolled in this prospective study to investigate their pre-, post-surgery, and delayed ratings of expected, experienced, and recalled pain intensity and unpleasantness, state anxiety and positive and negative affect. Results: Memory of postoperative pain was found to be accurate, regardless of the context of the surgery. Affective states in the postoperative period were congruent with those during pain recall. The study also revealed that in planned surgery context, remembered pain was predicted by experienced postoperative pain, cognitive functions, positive and negative affect; whereas in unplanned surgery context its significant predictors included age, anxiety, negative and positive affect. Discussion: This study suggests that older orthopaedic patients remember postoperative pain correctly after 3 months and that mood dependence effect may contribute to memory of pain. Pain recall after planned surgery appears to depend mainly on the actual experience, while following unplanned surgery it depends on affective factors. Present findings contribute to scarce knowledge about pain memory in older adults and have implications for patients' recovery and best practice in perioperative hospital care.
Article
The aim of the study was to assess the accuracy of the memory of experimentally induced pain and the affect that accompanies experimentally induced pain. Sixty-two healthy female volunteers participated in the study. In the first phase of the study, the participants received three pain stimuli and rated pain intensity, pain unpleasantness, state anxiety, and their positive and negative affect. About a month later, in the second phase of the study, the participants were asked to rate the pain intensity, pain unpleasantness, state anxiety, and the emotions they had felt during the first phase of the study. Both recalled pain intensity and recalled pain unpleasantness were found to be underestimated. Although the positive affect that accompanied pain was remembered accurately, recalled negative affect was overestimated and recalled state anxiety was underestimated. Experienced pain, recalled state anxiety, and recalled positive affect accounted for 44% of the total variance in predicting recalled pain intensity and 61% of the total variance in predicting recalled pain unpleasantness. Together with recent research findings on the memory of other types of pain, the present study supports the idea that pain is accompanied by positive as well as negative emotions, and that positive affect influences the memory of pain.
Article
Objective. : The study aimed to assess the accuracy of memories of both pain and the state anxiety that accompanies experimentally induced pain and to investigate the factors that influence the memory of experimental pain. Methods. : Forty-nine healthy female volunteers participated in the study. The participants received three electrocutaneous pain stimuli during the first phase of the study and rated the pain intensity, pain unpleasantness, and state anxiety they felt at that moment. Trait pain anxiety was measured by the Pain Anxiety Symptoms Scale and the Fear of Pain Questionnaire. During the second phase of the study, three or six months later (depending on the experimental group), the participants were asked to rate the pain intensity, pain unpleasantness, and state anxiety they had felt during the first phase of the study. Results. : Recalled pain intensity and unpleasantness and the state anxiety that accompanied the pain experience were remembered accurately, regardless of the recall delay. Both recalled pain intensity and unpleasantness were predicted by experienced pain, experienced and recalled state anxiety, and trait pain anxiety, that is, scores for physiological anxiety, cognitive anxiety, escape/avoidance, and severe pain. Conclusions. : The present study demonstrates that a specific type of trait anxiety (pain anxiety) influences the memory of pain. The study is not only the first to investigate the influence of trait anxiety on the memory of experimental pain, it also is the first study to determine the effect of a specific form of anxiety (pain anxiety) on the memory of experimentally induced pain.
Article
Oxytocin (OT) is a neurohypophysial hormone which has been found to play a central role in the regulation of human parturition. The most established role of oxytocin/oxytocin receptor (OT/OTR) system in human parturition is the initiation of uterine contractions, however, recent evidence have demonstrated that it may have a more complex role including initiation of inflammation, regulation of miRNA expression, as well as mediation of other non-classical oxytocin actions via receptor crosstalk with other G protein-coupled receptors (GPCRs). In this review we highlight both established and newly emerging roles of OT/OTR system in human parturition and discuss the expanding potential for OTRs as pharmacological targets in the management of term and preterm labour.
Chapter
Oxytocin is a nonapeptide produced by hypothalamic neurons, some of which project to the posterior pituitary, and others have targets in brain and spinal cord. Oxytocin secretion is important in parturition and essential for lactation. Oxytocin peptide and receptor gene regulation by sex steroids is described. The oxytocin receptor and post-receptor metabotropic pathways are detailed. Neural circuits controlling oxytocin neurons, transmitters they use and patterns of oxytocin secretion generated are described. Promotion by oxytocin in the brain of behaviors and emotionality conducive to reproduction and social interaction is critically reviewed. Possible consequences of derangement of central oxytocin functions are discussed.
Article
It is well established that the nonapeptide oxytocin (Oxt) is important for the neural modulation of behaviors in many mammalian species. Since its discovery in 1906 and synthesis in the early 1950s, elegant pharmacological work has helped identify specific neural substrates on which Oxt exerts its effects. More recently, mice with targeted genetic disruptions of the Oxt system, i.e. both the peptide and its receptor (the Oxtr), have further defined Oxt's actions and laid some important scientific groundwork for studies in other species. In this review we highlight the scientific contributions various mouse knockouts of the Oxt system have made to our understanding of Oxt function with regards to behavior. We specifically focus on how the use of these mice has shed light on our understanding of social recognition memory, maternal behavior, aggression, and several non-social behaviors. This article is protected by copyright. All rights reserved.
Article
Objective. To investigate whether pain catastrophizing and personality traits bias recalled ratings of acute pain in an experimental tonic pain model. Subjects and Setting. Fifty-six undergraduates (14 males) recruited from the University of Peradeniya (mean age 21.7 ± 0.8 SD years). Design and Methods. Participants completed the Pain Catastrophizing Scale and the Eysenck Personality Questionnaire. They were subjected to two cold pressor tests (dominant and non-dominant hands) and pain threshold, maximum pain intensity, and pain tolerance were recorded. One-week later, the maximum pain intensities of both hands were recalled and percentage distortions in recalling were calculated. Based on a 180 s cutoff, two participants were considered pain-insensitive during the test and were excluded from the analysis. Results. The maximum pain intensity was recalled with a moderate accuracy (Intraclass Correlation Coefficients = 0.68 for dominant and 0.59 for non-dominant hands). Hierarchical multiple regression analyses revealed that maximum pain intensity ( P < 0.001) and pain catastrophizing ( P < 0.001) contributed significantly to recalled pain intensity, and only pain catastrophizing contributed significantly ( P < 0.001) to percentage distortion in recalling with positive β-coefficients. Participants who consistently overrated pain for both hands in recalling scored significantly higher on catastrophizing ( P < 0.001). Conclusion. This study demonstrated that memory for painful events in healthy subjects was reasonably accurate over a period of 1 week. Pain catastrophizing biased pain recall, whereas among personality traits only neuroticism exhibited a weak positive association with the recalled ratings.
Article
Summary Oxytocin promotes social interactions and recognition of conspecifics that rely on olfaction in most species. The circuit mechanisms through which oxytocin modifies olfactory processing are incompletely understood. Here, we observed that optogenetically induced oxytocin release enhanced olfactory exploration and same-sex recognition of adult rats. Consistent with oxytocin’s function in the anterior olfactory cortex, particularly in social cue processing, region-selective receptor deletion impaired social recognition but left odor discrimination and recognition intact outside a social context. Oxytocin transiently increased the drive of the anterior olfactory cortex projecting to olfactory bulb interneurons. Cortical top-down recruitment of interneurons dynamically enhanced the inhibitory input to olfactory bulb projection neurons and increased the signal-to-noise of their output. In summary, oxytocin generates states for optimized information extraction in an early cortical top-down network that is required for social interactions with potential implications for sensory processing deficits in autism spectrum disorders.
Article
Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery.
Article
Dental patients generally recall more pain than they originally report, with ratings of pain related to state anxiety and dental fear, but the role of depression in recall of dental pain remains uncertain. This study examined the relative contributions of different variables in explaining dental pain recalled after tooth extraction. Patients presenting for tooth extraction, prior to extraction, rated their current dental pain and state anxiety, prediction of pain and state anxiety during extraction, depression, and dental fear. Immediately postprocedure and then 1 mo later, patients rated their pain and state anxiety during extraction. Hierarchical linear regression equations were used to explain variance in recalled pain and state anxiety. In addition, patients were divided into high and low dental fear and depression groups and compared on ratings of pain and state anxiety across time. In a final sample of 157 patients, the most important predictors of recalled pain were pain reported during extraction (β = .53) and recalled state anxiety (β = .52). Dental fear and depression had a significant interaction: only when patients reported less depression did those patients who reported more dental fear also report more pain than patients who reported less dental fear (P < 0.05, ω(2) = .07). Patients who reported more depression entered the dental operatory reporting more pain, but all patients generally reported less pain during extraction than they predicted or recalled. Memory of state anxiety and pain reported during tooth extraction, not depression or state anxiety at the time of extraction, were critical factors in memory of the pain associated with the procedure. At higher levels of depression, patients higher and lower in dental fear did not differ in report of pain. Future studies are needed to further clarify interactions of depression and dental fear over time.
Article
An ever-growing body of evidence suggests that the hypothalamic neuropeptide oxytocin plays a central role in the regulation of mammalian social behavior and relationships. Yet, mammalian social interactions are extremely complex, involving both approach and avoidance behaviors toward specific individuals. While in the past oxytocin was conceived merely as a prosocial molecule that nonselectively facilitated affiliative emotions and behavior, it is now recognized that oxytocin plays a role in a wide range of social relationships, some of which involve negative emotions such as fear, aggression, and envy and lead to avoidance behavior. However, the way by which a single molecule such as oxytocin contributes to contrasting emotions and opposite behaviors is yet to be discovered. Here, we discuss the role of oxytocin in the modulation of emotional memories in rodents, focusing on two paradigms: social recognition and fear conditioning, representing approach and avoidance behaviors, respectively. We review recent pioneering studies that address the complex effects of oxytocin in a mechanistic approach, using genetic animal models and brain region-specific manipulations of oxytocin activity. These studies suggest that the multiple roles of oxytocin in social and fear behavior are due to its local effects in various brain areas, most notably distinct regions of the amygdala. Finally, we propose a model explaining some of the contradictory effects of oxytocin as products of the balance between two networks in the amygdala that are controlled by the medial prefrontal cortex.
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