Intact pain modulation through manipulation of controllability and expectations in aging; ; ; ; ; ;
in European Journal of Pain (2021)
Intact pain modulation through manipulation of controllability and expectations in agingin European Journal of Pain (2021)
Distraction from pain: The role of selective attention and pain catastrophizingin European Journal of Pain (2020), 24(10), 1880-1891
Alterations in Neural Responses and Pain Perception in Older Adults During Distractionin Psychosomatic Medicine (2020), 82
Age-Related Changes in Pain Perception Are Associated With Altered Functional Connectivity During Resting Statein Frontiers in Aging Neuroscience (2020), 12(116),
The destruction of distraction? Neural mechanisms of reduced task-related analgesia with aging.Poster (2019, September 06)
The role of executive functions in task-related analgesiaPoster (2019, March)
Introduction: Recent research suggests that weaker executive functions may be linked to a higher risk of pain chronicity. However, little is known about how executive functions affect the modulation of acute pain. The present study aimed to investigate the impact of inhibitory control on the success of cognitive distraction from pain. Methods: Participants completed a battery of cognitive tasks (Go/NoGo, Color Stroop, Eriksen Flanker), assessing their cognitive inhibition and selective attention abilities. Additionally, self-report measures of pain catastrophizing and fear of pain were administered. In a pain distraction paradigm, participants completed either a cognitively demanding working memory task (2-back task) or a visually matched easy control task (target response task) while receiving warm or painful thermal stimuli to their left forearm. Nociceptive stimulus intensity was individually calibrated for each participant. Moreover, to maintain a similar level of task difficulty across participants, task speed was continuously adapted based on the participant's performance in the previous trials. Following each trial, participants rated the perceived intensity and unpleasantness of the thermal stimuli on visual analogue scales. Results: As expected, preliminary results indicate that the 2-back task, but not the target response task, successfully distracted participants from thermal pain, manifesting in significantly lower intensity and unpleasantness ratings. Importantly, the magnitude of the distraction effect was negatively associated with the Flanker effect. Discussion: In line with previous research, engaging in a cognitively demanding task led to significantly lower pain intensity and unpleasantness ratings when compared to an easy control task. Moreover, results indicate that better interference control abilities may predict greater task-related analgesia. Taken together, the results of the present study suggest that it is crucial to assess executive functions to develop a better understanding of the mechanisms behind cognitive distraction from pain.
Impact of controllability on pain and sufferingin Pain Reports (2018)
Introduction: Chronic pain and pain-related suffering are major health problems. The lack of controllability of experienced pain seems to greatly contribute to the extent of suffering. This study examined how controllability affects the perception of pain and pain related suffering, and the modulation of this effect by beliefs and emotions such as locus of control of reinforcement, pain catastrophizing, and fear of pain. Methods: Twenty-six healthy subjects received painful electric stimulation in both controllable and uncontrollable conditions. Visual analogue scales and the “Pictorial Representation of Illness and Self Measure” were used to assess pain intensity, unpleasantness, pain-related suffering, and the level of perceived control. We also investigated nonverbal indicators of pain and suffering such as heart rate, skin conductance, and corrugator electromyogram. Results: Controllability selectively reduced the experience of pain-related suffering, but did not affect pain intensity or pain unpleasantness. This effect was modulated by chance locus of control but was unrelated to fear of pain or catastrophizing. Physiological responses were not affected by controllability. In a second sample of 25 participants,we varied the instruction. The effect of controllability on pain-related suffering was only present when instructions focused on the person being able to stop the pain. Discussion: Our data suggest that the additional measure of pain-related suffering may be important in the assessment of pain and may be more susceptible to the effects of perceived control than pain intensity and unpleasantness. We also show that this effect depends on personal involvement.
Reduced modulatory effects of distraction on pain due to agingScientific Conference (2018, July)
Psychological, cognitive factors and contextual influences in pain and pain-related suffering as revealed by a combined qualitative and quantitative assessment approachin PLoS ONE (2018)
Previous psychophysiological research suggests that pain measurement needs to go beyond the assessment of Pain Intensity and Unpleasantness by adding the evaluation of Pain-Related Suffering. Based on this three-dimensional approach, we attempted to elucidate who is more likely to suffer by identifying reasons that may lead individuals to report Pain and Pain-Related Suffering more than others. A sample of 24 healthy participants (age range 18±33) underwent four different sessions involving the evaluation of experimentally induced phasic and tonic pain. We applied two decision tree models to identify variables (selected from psychological questionnaires regarding pain and descriptors from post-session interviews) that provided a qualitative characterization of the degrees of Pain Intensity, Unpleasantness and Suffering and assessed the respective impact of contextual influences. The overall classification accuracy of the decision trees was 75% for Intensity, 77% for Unpleasantness and 78% for Pain-Related Suffering. The reporting of suffering was predominantly associated with fear of pain and active cognitive coping strategies, pain intensity with bodily competence conveying strength and resistance and unpleasantness with the degree of fear of pain and catastrophizing. These results indicate that the appraisal of the three pain dimensions was largely determined by stable psychological constructs. They also suggest that individuals manifesting higher active coping strategies may suffer less despite enhanced pain and those who fear pain may suffer even under low pain. The second decision tree model revealed that suffering did not depend on pain alone, but that the complex rating-related decision making can be shifted by situational factors (context, emotional and cognitive). The impact of coping and fear of pain on individual Pain-Related Suffering may highlight the importance of improving cognitive coping strategies in clinical settings.
Maternal separation stress leads to resilience against neuropathic pain in adulthoodin Neurobiology of Stress (2018), 8
Neonatal maternal separation leads to a dampening of inflammation-related mechanical and thermal hypersensitivity in juvenile ratsin Neuroscience Letters (2018), 674
Early life stress reduces neuropathic pain in adulthood -is alteration of spinal microglial reactivity critically involved?Poster (2017, November 14)
Growing evidence underlines the association between early life adversity and persistent alterations of neural, endocrine and immune functions that may be accompanied by a host of disease patterns such as chronic pain in later life. Neuropathy is a debilitating condition presenting a substantial cooccurrence with stress related disorders. Despite the established overlapping of biochemical pathways involved in the etiology of these disorders, the intricacy of their mutual interdependence remains. In this context, immunocompetent cells are largely affected during chronic stress and are a key factor in the sensitization of nociceptive dorsal horn neurons. The goal of the present study was to investigate the impact of maternal separation (MS), a wellestablished model of early life stress in rodents, on chronic constriction injury (CCI)induced neuropathic pain and to reveal the relevance of spinal microglia activation and proinflammatory cytokine regulation. For this purpose 12 groups of rats were exposed to different combinations of stress condition, CCIinjury and pharmacological treatment. Noxious sensitivity was tested during baseline conditions as well as during subsequent neuropathic and pharmacological treatment conditions. Von Frey hair and the cold plate tests were used for the assessment of mechanical and cold hyperalgesia/allodynia. Amphotericin B, a substance known to activate monocytes and macrophages in the periphery and microglial cells in the CNS was administered to subgroups of animals. At the end of the protocol, rats were sacrificed to assess microglial activation using qPCR and immunohistochemistry. Our main finding was that maternal separation led to a reduction of CCIrelated pain hypersensitivity (thermal and mechanical hyperalgesia/allodynia). We concomitantly observed a downregulation of Iba 1, mRNA a marker of microglial cells, and of IL1β mRNA, a proinflammatory cytokine that may be released by microglia. According to preliminary results, Amphotericin B in turn seemed to enhance CCI related pain sensitivity, possibly via an activation of microglia. Our results show that MS may lead to a reduction of neuropathy relatedpain in adult age. Stress related dampening of spinal microglial reactivity may play a critical role in this context.
Assessing suffering in experimental pain models: psychological and psychophysiological correlatesin Zeitschrift für Psychologie (2017), 225(1), 45-53
Although suffering is a central issue in pain, there is only little research on this topic. The aim of this study was to assess suffering in an experimental context using various stimulation methods and durations, and to examine which psychological or psychophysiological measures covary with pain-related suffering. Twenty-one healthy volunteers participated in two experiments in which we used tonic thermal and phasic electric stimuli with short and long stimulus durations. The participants rated pain intensity, unpleasantness, and pain-related suffering on separate visual analog scales (VAS) and completed the Pictorial Representation of Illness and Self Measure (PRISM), originally developed to assess suffering in chronic illness. We measured heart rate, skin conductance responses (SCRs), and the electromyogram (EMG) of the musculus corrugator supercilii. For both heat and electric pain, we obtained high ratings on the suffering scale confirming that suffering can be evoked in experimental pain conditions. Whereas pain intensity and unpleasantness were highly correlated, both scales were less highly related to suffering, indicating that suffering is distinct from pain intensity and unpleasantness. Higher suffering ratings were associated with more pronounced fear of pain and increased private self-consciousness. Pain-related suffering was also related to high resting heart rate, increased SCR, and decreased EMG during painful stimulation. These results offer an approach to the assessment of suffering in an experimental setting using thermal and electric pain stimulation and shed light on its psychological and psychophysiological correlates.
Painful decisions: How classifying sensations can change the experience of painin European Journal of Pain (2017)
Background: Categorizing perceptual stimuli is a mechanism for facilitating the processing of sensory input from our environment. This facilitation of perception is achieved through generalization (assimilation) of stimulus characteristics within categories and accentuation between categories. These categorization processes have been demonstrated in visual, auditory, tactile and social perception, but never in pain perception. Method: We presented participants with six thermal noxious stimuli, increasing in steps of 0.5 °C. In an experimental group, stimuli were assigned to two categories labelled A and B containing the three lower (A1, A2, A3) and three higher (B1, B2, B3) stimuli. A control group did not receive such category information (stimuli were labelled S1–S6). In a first part of the experiment, participants simply rated pain intensity and unpleasantness for all stimuli. In a second part, we presented stimuli without labels and participants had to identify the label of each stimulus. Results: We found evidence for categorization effects in both pain ratings and stimulus identification data. In particular, unpleasantness ratings within categories were more similar to each other, and ratings between categories less similar, in the experimental compared to control group. Participants in the experimental group also confused stimuli more often within than between categories, and were more confident about category membership of stimuli at the category border, compared to participants in the control group. Conclusions: Mere category information, using abstract category labels, significantly changes pain perception. Implications for our understanding of cognitive pain modulation mechanisms, as well as clinical implications of categorization effects are discussed. Significance: Categorization effects in pain perception are demonstrated. Classifying and labelling painful events can modulate early perceptual processes, lead to under- or overestimation of pain symptoms and affect decision-making behaviour related to pain.
The role of cognitive reappraisal in placebo analgesia: an fMRI studyin Social Cognitive and Affective Neuroscience (2017), (2017), 1-10
Placebo analgesia (PA) depends crucially on the prefrontal cortex (PFC), which is assumed to be responsible for initiating the analgesic response. Surprisingly little research has focused on the psychological mechanisms mediated by the PFC and underlying PA. One increasingly accepted theory is that cognitive reappraisal—the reinterpretation of the meaning of adverse events—plays an important role, but no study has yet addressed the possible functional relationship with PA. We studied the influence of individual differences in reappraisal ability on PA and its prefrontal mediation. Participants completed a cognitive reappraisal ability task, which compared negative affect evoked by pictures in a reappraise versus a control condition. In a subsequent fMRI session, PA was induced using thermal noxious stimuli and an inert skin cream. We found a region in the left dorsolateral PFC, which showed a positive correlation between placebo-induced activation and (i) the reduction in participants’ pain intensity ratings; and (ii) cognitive reappraisal ability scores. Moreover, this region showed increased placebo-induced functional connectivity with the periaqueductal grey, indicating its involvement in descending nociceptive control. These initial findings thus suggest that cognitive reappraisal mechanisms mediated by the dorsolateral PFC may play a role in initiating pain inhibition in PA
Chronic Social Stress Time-Dependently Affects Neuropathic Pain-Related Cold Allodynia and Leads to Altered Expression of Spinal Biochemical Mediatorsin Frontiers in Behavioral Neuroscience (2017), 11
Clinical data have shown that chronic exposure to stress may be accompanied by an enhancement of inflammation-related pain sensitivity. In this context, little is however known on the impact of stress on neuropathic pain. In the present study we addressed this issue by combining the chronic constriction injury (CCI) model with an ongoing social stress (OSS) paradigm. Cold plate and von Frey tests were performed in 48 rats divided into four groups: OSS exposed to OSS, CCI subjected to chronic nerve constriction, OSS+CCI with a combination of neuropathy and stress and CON, a control group lacking any manipulation. While we did not observe any stress-related differences in mechanical sensitivity throughout the observation period, CCI rats were more sensitive to cold stimulation than OSS+CCI in the initial phase of neuropathy. A switch was observed at a later stage, leading to a hypersensitivity of the OSS+CCI compared to the CCI rats. At this time point we investigated the spinal mRNA expression of neuron and glia related molecules potentially involved in neuropathic pain and stress. The combination of psychosocial stress and neuropathic pain seemed to enhance glial cell activation, pro-inflammatory cytokine and neurotrophic factor mRNA levels, rather than glutamatergic transmission. Our data show that long lasting social stress may lead to time-dependent alteration of neuropathy-related cold pain sensitivity while mechanicallyinduced pain remains unchanged.
Facteurs psychologiques, cognitifs et les influences contextuelles dans la douleur et la souffrance liée à la douleurPoster (2016, November)
Reliability of conditioned pain modulation for the assessment of endogenous pain control pathwaysin Neurology, Psychiatry and Brain Research (2016)
Pain and reéated sufering increase interoceptive awarenes by focusing attention to internal bodily sensationsScientific Conference (2016, July 14)
Vaguely mediated heart rate variability promotes the perception of paradoxical painin Journal of Psychophysiology (2016)
Self-regulation mechanisms are governed by prefrontal inhibitory processes and play a crucial role in the modulation of pain. In the present study the thermal grill paradigm was used to investigate the association of vagally mediated resting heart rate variability, a psychophysiological marker of trait self-regulatory capacity, with paradoxical pain sensations induced by non-noxious stimulation. This thermal grill illusion is only perceived by part of the tested individuals. The mechanisms underlying the observed inter-individual differences in paradoxical pain sensitivity are largely unknown. During the experimental task, a temperature combination of 15° C and 41° C was set at the glass tubes of the thermal grill. The fifty-two healthy participants placed their dominant hand on the grill for a duration of one minute. The magnitude of sensory and affective pain sensations perceived during stimulation was assessed with numerical rating scales. Before stimulation, a short-term electrocardiogram was recorded to compute vagally mediated heart rate variability at rest. Logistic regression analyses revealed that participants with higher vagal tone were significantly more likely to perceive the thermal grill illusion than subjects displaying lower resting heart rate variability. Paradoxical pain sensations were primarily predicted by normalized respiratory sinus arrhythmia. Our results confirm that the magnitude of vagally mediated resting heart rate variability is associated with the individual disposition to illusive pain perceptions. Since the latter is considered to be a marker of trait self-regulation ability, the present findings may corroborate and complement previous evidence for an impact of psychological characteristics on paradoxical pain sensitivity.
Blood pressure and the perception of illusive painin Psychophysiology (2016), 53(8), 1282-1291
Numerous studies have documented an inverse relationship between blood pressure and sensitivity to experimental nociceptive stimulation. The present study aimed to investigate possible associations between blood pressure and the occurrence and intensity of paradoxical pain induced by the thermal grill paradigm. Thirty-one healthy subjects were stimulated three times for 1 minute with the non-noxious temperatures of 15°C and 41°C set at the interlaced cold and warm bars of a water bath-driven thermal grill. Blood pressure and heart rate were recorded concomitantly. On account of previous observations of an association between the sensitivity of the cardiac baroreflex and pain perception, this parameter was additionally obtained. Numerical rating scales were used to quantify subjective pain intensity and pain unpleasantness; subjects were classified as responders and non-responders to thermal grill stimulation based on pain intensity ratings. Responders exhibited lower systolic and diastolic blood pressure than non-responders, and inverse linear associations arose between blood pressure and pain intensity and unpleasantness. Baroreflex sensitivity was unrelated to pain ratings. The findings confirmed the hypothesis of a blood pressure dependence of paradoxical pain and support the notion that the cardiovascular and pain regulatory systems interact not only in the processing of pain elicited by noxious input, but also in non-noxiously generated illusive pain. While this finding is not consistent with the assumption of an involvement of the baroreflex system in mediating the observed interaction, psychological traits and neurochemical factors are alternatively considered.
Peripheral and central alterations affecting spinal nociceptive processing and pain at adulthood in rats exposed to neonatal maternal deprivationin European Journal of Neuroscience (2016)
Peripheral and central alterations affecting spinal nociceptive processing and pain at adulthood in rats exposed to maternal separationin European Journal of Neuroscience (2016)
Inter-individual differences in cardiovascular reactivity and the perception of the thermal grill illusion of painSpeeches/Talks (2015)
Background: Evidence has been given that there exists a functional relationship between the cardiovascular and the pain regulatory system. Alterations in blood pressure and concomitant changes in baroreceptor activation contribute to the modulation of pain sensitivity It could be shown that blood pressure, baroreflex sensitivity, and cardiac vagal tone (indexed by heart rate variability, HRV) are inversely associated to pain sensitivity. We aimed assessing the same cardiovascular parameters in a thermal grill paradigm to test the assumption of a relationship between inter-individual differences in autonomic cardiac control and the perception of the thermal grill illusion of pain (TGI). Methods: All participants (N = 52) were stimulated three times during one minute with the temperatures of 15°C and 41°C set at the interlaced cold and warm bars of the water-bath driven thermal grill. Blood pressure and heart rate were recorded concomitantly. Numerical rating scales (NRS; 0–100) were used to quantify subjective paradoxical pain intensity and pain unpleasantness perceptions. Results: A positive association between cardiac vagal tone and paradoxical pain sensitivity could be revealed. Higher resting HRV, as expressed by higher respiratory sinus arrhythmia (RSA), made it overall more likely to perceive the TGI. In contrast, blood pressure and the susceptibility to the TGI were inversely related. Volunteers displaying higher spontaneous blood pressure values in the first thermal grill stimulation phase did not feel the illusive pain as compared to those who presented significantly lower sympathetic arousal and perceived the TGI. Conclusion: The present physiological findings complement previous evidence of an impact of psychological characteristics on the individual disposition to paradoxical pain perceptions.
Relationship between cardiovascular reactivity and the perception of the thermal grill illusion of painPoster (2015, September 03)
Alterations in blood pressure (BP) and concomitant changes in baroreceptor activation contribute to the modulation of pain sensitivity to warrant homeostatic regulation processes [1][2]. Numerous pain studies have described an inverse relationship between BP and nociceptive sensitivity [3][4][5]. It is not known whether a similar relationship plays a role in the framework of the induction of pain in the absence of noxious stimulation. The thermal grill (TG) paradigm is commonly used to trigger this type of paradoxical pain also termed thermal grill illusion of pain (TGI). The goal of the present study was to explore the relationship between cardiovascular activity/reactivity and paradoxical pain sensitivity to get additional insight in the variability of responsiveness (responders and non-responders) to TG stimulation described in the literature [6][7]. We hypothesized that higher BP would be associated with stronger pain inhibitory effects in participants not perceiving the thermal grill illusion of pain (TGI). We moreover expected that the perception of paradoxical pain in the responder group would be paired with lower BP. We tested this hypothesis by comparing both groups with respect to their spontaneous cardiovascular activity (recorded in resting conditions) and their cardiovascular responses to TG stimulation.
Prefrontal activation during placebo analgesia is related to cognitive reappraisalPoster (2015, September)
Suffering as an independent component of the experience of painin European Journal of Pain (2015)
Pain processing and coping with social stress in rats exposed to adverse early life eventsScientific Conference (2015)
Vorwort der Koautorenin Schmithüsen, Franziska (Ed.) Lernskript Psychologie - Die Grundlagenfächer kompakt (2015)
Corticosterone analgesia is mediated by the spinal production of neuroactive metabolites that enhance GABAergic inhibitory transmission on dorsal horn rat neurons.in The European journal of neuroscience (2015)
Corticosterone (CORT) is a glucocorticoid produced by adrenal glands under the control of the hypothalamic-pituitary-adrenal axis. Circulating CORT can enter the central nervous system and be reduced to neuroactive 3alpha5alpha-reduced steroids, which modulate GABAA receptors. In the dorsal spinal cord, GABAergic transmission modulates integration of nociceptive information. It has been shown that enhancing spinal inhibitory transmission alleviates hyperalgesia and allodynia. Therefore, the spinal neuronal network is a pivotal target to counteract pain symptoms. Thus, any increase in spinal 3alpha5alpha-reduced steroid production enhancing GABAergic inhibition should reduce nociceptive message integration and the pain response. Previously, it has been shown that high levels of plasma glucocorticoids give rise to analgesia. However, to our knowledge, nothing has been reported regarding direct non-genomic modulation of neuronal spinal activity by peripheral CORT. In the present study, we used combined in vivo and in vitro electrophysiology approaches, associated with measurement of nociceptive mechanical sensitivity and plasma CORT level measurement, to assess the impact of circulating CORT on rat nociception. We showed that CORT plasma level elevation produced analgesia via a reduction in C-fiber-mediated spinal responses. In the spine, CORT is reduced to the neuroactive metabolite allotetrahydrodeoxycorticosterone, which specifically enhances lamina II GABAergic synaptic transmission. The main consequence is a reduction in lamina II network excitability, reflecting a selective decrease in the processing of nociceptive inputs. The depressed neuronal activity at the spinal level then, in turn, leads to weaker nociceptive message transmission to supraspinal structures and hence to alleviation of pain.
Lernskript Psychologie: Kapitel 4: Biopsychologiein Schmithüsen, Franziska (Ed.) Lernskript Psychologie (2014)
Experimental induction of suffering: why suffering is not the same as unpleasantnessScientific Conference (2014, October 10)
Introducing the dimension of suffering to mechanically induced phasic and tonic painScientific Conference (2014, October 10)
<the impact of self and controllability on diferent pain dimensionsScientific Conference (2014, October 10)
Identification of psychological traits that are critically involved in the occurrence of experimentally induced sufferingPoster (2014, October 07)
Vagally mediated heart rate variability is a predictor for the occurrence of the thermal grill-induced pain illusionPoster (2014, October)
Aim: Unpleasantness and negative affect accompany the sensory experience of pain. Both components of pain are heavily influenced by cognitive and emotional processes. In this framework, alterations in baroreceptor reactivity and concomitant changes in cardiac rhythm and blood pressure related to these processes contribute to the modulation of pain sensitivity. Furthermore, self-regulatory capacity has been shown to play a major role in the regulation of cognitive, affective, and behavioural reactions to adverse contexts. These regulatory mechanisms include adjustment of cardiovascular activity and heavily depend on prefrontal cortical processing. Vagally mediated heart rate variability (HRV) at rest is an indicator of the prefrontally modulated vagal activation and has been used as a psychophysiological marker for self-regulatory capacity. The present study investigated the predictive value of the trait self-regulation in the triggering of the thermal grill-induced pain illusion (TGI). We hypothesized inter-individual differences in paradoxical pain perception to be predicted by self-regulatory capacity in a way that participants displaying lower levels of self-regulation should be more likely to perceive the painful grill illusion than subjects with relatively higher self-regulation ability. Methods: A total of 54 healthy participants were recruited among university students and staff. A custom-built, water-bath driven thermal grill device, with interlaced cold and warm glass tubes, was used for the induction of the TGI. A pre-set temperature combination of 15°C and 41°C was applied to the palm of the dominant hand with stimulus durations of 1 min. Subsequent control conditions consisted in the interlaced combination of a baseline temperature of 32°C with one of the stimulus temperatures mentioned above. The procedure was repeated three times. The volunteers used numerical rating scales ranging from 0-100 to rate sensory and affective pain perceptions in intervals of 15 seconds. Vagally mediated HRV at rest was assessed prior to the thermal stimulation protocols. Results: Time-domain components of HRV used as graded indicators of parasympathetic activity and of the extent of self-regulation significantly predicted the possibility of an occurrence of pain and unpleasantness sensations in response to thermal grill stimulation (p <.05). Participants characterized in this way were more likely to express paradoxical pain than subjects not displaying similar levels of HRV. Conclusion: The present results support previous findings indicating an impact of several psychological traits on the individual disposition to paradoxical pain perceptions. Self-regulation ability, operationalized as vagally mediated heart rate variability, can partially explain the probability of perceived pain in response to non-noxious thermal grill stimulation.
Rumination and interoceptive accuracy predict the occurrence of the thermal grill illusion of painin BMC Psychology (2014), 2(22),
Background: While the physiological mechanisms of the thermal grill illusion of pain (TGI) are largely understood, psychological determinants remain mainly unknown. The present study aimed to investigate whether cognitive and affective personality traits encompassing rumination, interoception and suggestibility contribute to the inducibility of paradoxical pain. Methods: The dominant hand of 54 healthy volunteers was stimulated with a water-bath driven thermal grill providing an interlaced temperature combination of 15 and 41°C. Pain intensity and pain unpleasantness perceptions were rated on a numerical scale (NRS). Traits were assessed via questionnaires, the heartbeat-tracking task, and warmth suggestions. Results: Logistic regression analyses uncovered trait rumination and interoceptive accuracy (IA) as major predictors of the likelihood of the illusive pain occurrence (all p < .05). Rumination and suggestibility had an impact on unpleasant pain perceptions. Conclusion: Our findings demonstrate a significant influence of psychological aspects on the individual disposition to the painful grill illusion (PGI).
Neonatal maternal separation stress alters neuropathic pain behaviour and spinal nociceptive processing in ratsScientific Conference (2014)
Aims Early life stress enhances vulnerability to metabolic and mental disorders in adulthood. Altered pain sensitivity and dysfunctional emotional processing have been described in this context. We assessed the impact of neonatal maternal separation (MS) on chronic constriction injury (CCI) induced neuropathic pain behavior and biochemical spinal processing in early adulthood. Methods Four groups of rats were tested: Controls, MS, CCI, MS+CCI. For MS, pups were separated from the dam from postnatal day 2 to 12 for 3 hours per day. At an age of 7 weeks mechanical and thermal pain thresholds where assessed by the von Frey and the cold plate test. CCI surgery was performed in two of the experimental groups and behavioural measurements were continued until day 21 post surgery. After decapitation spinal cord levels L4/L5 were removed and total RNA was extracted to perform qPCR. Results MS alone did not affect pain thresholds. Surprisingly, MS+CCI rats were less sensitive to mechanical and thermal stimuli compared to CCI. Regarding the biochemical data, MS as well as MS+CCI led to an upregulation of glial markers, cytokines and growth factors and to a downregulation of glutamate receptors and transporters. Conclusion Behavioral and biochemical data are conflicting. The reduced pain sensitivity in MS animals is in contrast to activation of glia and enhanced expression of cytokines but in line with reduced glutamatergic signalling. Since MS and MS+CCI groups did not differ, pain-related processing may have been outweighed by stress-related programming of biochemical reactivity.
Glucocorticoid-Mediated Enhancement of Glutamatergic Transmission May Outweigh Anti-Inflammatory Effects under Conditions of Neuropathic Pain.in PloS one (2014), 9(3), 91393
At the clinical level comorbidity between chronic pain and dysfunctional hypothalamus-pituitary-adrenal (HPA) axis is well established. We aimed to identify causal relationships in a model of neuropathic pain (chronic constriction injury, CCI) by studying the effects of glucocorticoid receptor agonist (dexamethasone) and antagonist (RU-486) administration on pain behavior and spinal biochemical mediators. Daily injections were performed in Sprague Dawley rats. Weight, plasma corticosterone levels and mechanical pain thresholds were assessed before and during 21 days post-CCI. At days four and 21 we investigated the mRNA expression of spinal mediators. In the dexamethasone-injected group, we observed a diminution of body weight and plasma corticosterone levels during the 21 days post surgery period and a more pronounced pain sensitivity until day 7 post-CCI. This enhanced pain sensitivity in the early period following nerve injury was accompanied by a transient increase of the glutamate receptors mGluR5 and NMDA at day 4. However, at this time point we did not observe any effect of the agonist/antagonist injections on the mRNA expression of pro-inflammatory cytokines. The RU-486-injected rats showed a slight mechanical hypoalgesia until 7 days post-CCI, but without any significant correlation with the expression of the measured markers. Our results indicate that glucocorticoid-related modulations of neuropathic pain processing may rather depend on a modification of glutamatergic transmission than on a change in pro-inflammatory cytokine expression.
Beep Tones Attenuate Pain following Pavlovian Conditioning of an Endogenous Pain Control Mechanismin PLoS ONE (2014), 9(2), 88710
Heterotopic noxious counter-stimulation (HNCS) is commonly used to study endogenous pain control systems. The resulting pain inhibition is primarily based on spinal cord-brainstem loops. Recently, functional imaging studies have shown that limbic structures like the anterior cingulate cortex and amygdala are also implicated. Since these structures are involved in learning processes, it is possible that the HNCS-induced pain inhibition may depend on specific cues from the environment that have been associated with pain reduction through associative learning. We investigated the influence of Pavlovian conditioning on HNCS-induced pain inhibition in 32 healthy subjects by using a differential conditioning paradigm in which two different acoustic stimuli were either repeatedly paired or unpaired with HNCS. Series of noxious electrical pulse trains delivered to the non-dominant foot served as test stimuli. Diffuse noxious inhibitory control (DNIC)-like effects were induced by concurrent application of tonic HNCS (immersion of the contralateral hand in ice water). Subjective pain intensity and pain unpleasantness ratings and electromyographic recordings of the facial corrugator muscle and the nocifensive RIII flexion reflex were used to measure changes in pain sensitivity. HNCS induced significant pain and reflex inhibitions. In the post-conditioning phase, only the paired auditory cue was able to significantly reduce pain perceptions and corrugator muscle activity. No conditioned effect could be observed in RIII reflex responses. Our results indicate that the functional state of endogenous pain control systems may depend on associative learning processes that, like in the present study, may lead to an attenuation of pain perception. Similar albeit opposite conditioning of pain control mechanisms may significantly be involved in the exacerbation and chronification of pain states.
Differential neuropathic pain sensitivity and expression of spinal mediators in Lewis and Fischer 344 rats.in BMC neuroscience (2014), 15(1), 35
BACKGROUND: Altered hypothalamo-pituitary-adrenal (HPA) axis activity may be accompanied by a modulation of pain sensitivity. In a model of neuropathic pain (chronic constriction injury, CCI) we investigated the onset and maintenance of mechanical allodynia/hyperalgesia and the expression of biochemical mediators potentially involved in spinal cell modulation in two rat strains displaying either hypo- (Lewis-LEW) or hyper- (Fischer 344-FIS) reactivity of the HPA axis. RESULTS: Mechanical pain thresholds and plasmatic corticosterone levels were assessed before and during periods of 4 or 21 days following CCI surgery. At the end of the respective protocols, the mRNA expression of glial cell markers (GFAP and Iba1) and glutamate transporters (EAAT3 and EAAT2) were examined. We observed a correlation between the HPA axis reactivity and the pain behavior but not as commonly described in the literature; LEW rats seemed to be less sensitive than FIS from 4 to 14 days after the CCI surgery when looking at the mechanical allodynia/hyperalgesia. However, the biochemical spinal markers expression we observed is conflicting. CONCLUSION: We did not find a specific causal relation between the pain behavior and the glial cell activation or the expression of the glutamate transporters, suggesting that the interaction between the HPA axis and the spinal activation pattern is more complex in a context of neuropathic pain.
Plasma glucocorticoids differentially modulate phasic and tonic GABA inhibition during early postnatal development in rat spinal lamina II.in Neuroscience letters (2014), 578
Nociceptive processing is tuned by GABAA receptor-mediated inhibition in the spinal cord dorsal horn that undergoes postnatal maturation in rodents. These GABAergic inhibitory postsynaptic currents (IPSCs) are modulated by 3alpha5alpha-reduced steroids during early postnatal development in spinal cord lamina II. Thus an enhanced phasic inhibition is present in neonates and decreases over time. GABA can also activate extrasynaptic receptors, giving rise to tonic inhibition. In this study, we characterized the contribution of plasma corticosterone (CORT) to postnatal maturation of spinal phasic and, for the first time, tonic GABAergic inhibitions. We used Fisher and Lewis rat strains displaying respectively high and low hypothalamic-pituitary-adrenal axis reactivity, compared to control Sprague-Dawley rats. Measured plasma CORT levels were significantly higher in Fisher rats, which also displayed significantly higher mechanical nociceptive thresholds, supporting the hypothesis of an antinociceptive action of CORT. Recorded GABAA IPSCs shortened during maturation in all strains while remaining larger in Fisher rats. Blocking the 5alpha-reduction of steroids in Fisher rats produced a further decrease of IPSC deactivation time constant. In contrast, GABAA tonic inhibition progressively increased during maturation, without any difference among strains. In conclusion, we show that both phasic and tonic GABAergic inhibitions undergo postnatal maturation in lamina II. Moreover spinal production of 3alpha5alpha-reduced steroids that presumably derive from plasma CORT is correlated to spinal GABAA phasic (but not tonic) inhibition and to mechanical nociceptive thresholds.
Rumination, interoceptive awareness and suggestibility predict the occurrence of the thermal grill illusionPoster (2013, October 10)
ruminationInterposed non-noxious cold and warm cutaneous stimuli applied via a thermal grill have repeatedly been shown to generate a paradoxical pain sensation, also described as ‘thermal grill illusion of pain’. According to the ‘central disinhibition theory’ proposed by Craig and Bushnell [1], the pain phenomenon commonly qualified as burning can be explained by “an unmasking of cold-evoked activity of polymodal nociceptive lamina I spinothalamic neurons (activation by polymodal Cnociceptors) resulting from the reduction of normal coldevoked activity of thermoreceptive lamina I spinothalamic neurons (activation by Aδ cooling thermoreceptors) by spatial summation of the simultaneous warm stimuli in the thermoreceptive but not the nociceptive neurons.” Since a significant part of the tested subjects do however not display the thermal grill percept, it may be hypothesized that not only physiological-, but also psychological determinants play a crucial role in the generation of the paradoxical pain. Sad mood [2] and anxiety [3] have already been proposed as relevant psychological factors. The aim of the present research consisted in validating our custom made, water-driven and fMRI compatible thermal grill device [4], in identifying thermal grill ‘responders’ and ‘non-responders’ and in investigating whether different personality traits or states constitute predictors for the elicitation of the thermal grill illusion.
Chronic psychosocial stress affects neuropathic pain behavior and spinal nociceptive processing.in EFIC 2013 Abstractbook, p707, No 575 (2013)
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