Startle modulation by heat pain with varying threat levels in chronic pain patients and pain-free controls.
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ABSTRACT:
SUBMITTER: Horn-Hofmann C
PROVIDER: S-EPMC5546785 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:This study evaluated the relationship between neuroticism (N), a probable risk factor for emotional disorders, and modulation of startle reflexes (SRs).One hundred thirty-two adolescents with varying levels of N but without anxiety or depressive disorders were evaluated in contextual cue and explicit threat cue paradigms.Within the explicit threat cue paradigm, N potentiated SRs more in conditions that were intermediately associated with threat of an aversive biceps contraction than conditions that were the furthest from and conditions that were the closest to the same threat. Also, N potentiated SRs across the entire experiment, regardless of experimental conditions, in male and not in female subjects.These results suggest that adolescents with high levels of N show greater sensitivity to contexts intermediately associated with threat. Results are discussed in comparison with other studies of groups at risk for anxiety and depressive disorders.
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Project description:AbstractPain-related learning mechanisms likely play a key role in the development and maintenance of chronic pain. Previous smaller-scale studies have suggested impaired pain-related learning in patients with chronic pain, but results are mixed, and chronic back pain (CBP) particularly has been poorly studied. In a differential conditioning paradigm with painful heat as unconditioned stimuli, we examined pain-related acquisition and extinction learning in 62 patients with CBP and 61 pain-free healthy male and female volunteers using valence and contingency ratings and skin conductance responses. Valence ratings indicate significantly reduced threat and safety learning in patients with CBP, whereas no significant differences were observed in contingency awareness and physiological responding. Moreover, threat learning in this group was more impaired the longer patients had been in pain. State anxiety was linked to increased safety learning in healthy volunteers but enhanced threat learning in the patient group. Our findings corroborate previous evidence of altered pain-related threat and safety learning in patients with chronic pain. Longitudinal studies exploring pain-related learning in (sub)acute and chronic pain are needed to further unravel the role of aberrant pain-related learning in the development and maintenance of chronic pain.
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Project description:Approximately 1.7 million youth suffer from debilitating chronic pain in the US alone, conferring risk of continued pain in adulthood. Aberrations in threat-safety (T-S) discrimination are proposed to contribute to pain chronicity in adults and youth by interacting with pain-related distress. Yet, few studies have examined the neural circuitry underlying T-S discrimination in patients with chronic pain or how T-S discrimination relates to pain-related distress. In this study, 91 adolescents (10-24 years; 78 females) including 30 chronic pain patients with high pain-related distress, 29 chronic pain patients with low pain-related distress, and 32 healthy peers without chronic pain completed a developmentally appropriate T-S learning paradigm. We measured self-reported fear, psychophysiology (skin conductance response), and functional magnetic resonance imaging responses (N = 72 after functional magnetic resonance imaging exclusions). After controlling for age and anxiety symptoms, patients with high pain-related distress showed altered self-reported fear and frontolimbic activity in response to learned threat and safety cues compared with both patients with low pain-related distress and healthy controls. Specifically, adolescent patients with high pain-related distress reported elevated fear and showed elevated limbic (hippocampus and amygdala) activation in response to a learned threat cue (CS+). In addition, they showed decreased frontal (vmPFC) activation and aberrant frontolimbic connectivity in response to a learned safety cue (CS-). Patients with low pain-related distress and healthy controls appeared strikingly similar across brain and behavior. These findings indicate that altered T-S discrimination, mediated by frontolimbic activation and connectivity, may be one mechanism maintaining pain chronicity in adolescents with high levels of pain-related distress.
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Project description:Previous studies have not clearly demonstrated whether motivational tendencies during reward feedback are mainly characterized by appetitive responses to a gain or mainly by aversive consequences of reward omission. In the current study this issue was addressed employing a passive head or tails game and using the startle reflex as an index of the appetitive-aversive continuum. A second aim of the current study was to use startle-reflex modulation as a means to compare the subjective value of monetary rewards of varying magnitude. Startle responses after receiving feedback that a potential reward was won or not won were compared with a baseline condition without a potential gain. Furthermore, startle responses during anticipation of no versus potential gain were compared. Consistent with previous studies, startle-reflex magnitudes were significantly potentiated when participants anticipated a reward compared to no reward, which may reflect anticipatory arousal. Specifically for the largest reward (20-cents) startle magnitudes were potentiated when a reward was at stake but not won, compared to a neutral baseline without potential gain. In contrast, startle was not inhibited relative to baseline when a reward was won. This suggests that startle modulation during feedback is better characterized in terms of potentiation when missing out on reward rather than in terms of inhibition as a result of winning. However, neither of these effects were replicated in a more targeted second experiment. The discrepancy between these experiments may be due to differences in motivation to obtain rewards or differences in task engagement. From these experiments it may be concluded that the nature of the processing of reward feedback and reward cues is very sensitive to experimental parameters and settings. These studies show how apparently modest changes in these parameters and settings may lead to quite different modulations of appetitive/aversive motivation. A future experiment may shed more light on the question whether startle-reflex modulation after feedback is indeed mainly characterized by the aversive consequences of reward omission for relatively large rewards.
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Project description:The p53-inducible TIGAR protein functions as a fructose-2,6-bisphosphatase, promoting the pentose phosphate pathway and helping to lower intracellular reactive oxygen species (ROS). ROS functions in the regulation of many cellular responses, including autophagy--a response to stress conditions such as nutrient starvation and metabolic stress. In this study, we show that TIGAR can modulate ROS in response to nutrient starvation or metabolic stress, and functions to inhibit autophagy. The ability of TIGAR to limit autophagy correlates strongly with the suppression of ROS, with no clear effects on the mTOR pathway, and is p53 independent. The induction of autophagy in response to loss of TIGAR can function to moderate apoptotic response by restraining ROS levels. These results reveal a complex interplay in the regulation of ROS, autophagy and apoptosis in response to TIGAR expression, and shows that proteins similar to TIGAR that regulate glycolysis can have a profound effect on the autophagic response through ROS regulation.
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Project description:BackgroundLearning to predict threatening events enables an organism to engage in protective behavior and prevent harm. Failure to differentiate between cues that truly predict danger and those that do not, however, may lead to indiscriminate fear and avoidance behaviors, which in turn may contribute to disability in people with persistent pain. We aimed to test whether people with persistent neck pain exhibit contingency learning deficits in predicting pain relative to pain-free, gender-and age-matched controls.MethodWe developed a differential predictive learning task with a neck pain-relevant scenario. During the acquisition phase, images displaying two distinct neck positions were presented and participants were asked to predict whether these neck positions would lead to pain in a fictive patient with persistent neck pain (see fictive patient scenario details in Appendix A). After participants gave their pain-expectancy judgment in the hypothetical scenario, the verbal outcome (PAIN or NO PAIN) was shown on the screen. One image (CS+) was followed by the outcome "PAIN", while another image (CS-) was followed by the outcome "NO PAIN". During the generalization phase, novel but related images depicting neck positions along a continuum between the CS+ and CS- images (generalization stimuli; GSs) were introduced to assess the generalization of acquired predictive learning to the novel images; the GSs were always followed by the verbal outcome "NOTES UNREADABLE" to prevent extinction learning. Finally, an extinction phase was included in which all images were followed by "NO PAIN" assessing the persistence of pain-expectancy judgments following disconfirming information.ResultsDifferential pain-expectancy learning was reduced in people with neck pain relative to controls, resulting from patients giving significantly lower pain-expectancy judgments for the CS+, and significantly higher pain-expectancy judgments for the CS-. People with neck pain also demonstrated flatter generalization gradients relative to controls. No differences in extinction were noted.DiscussionThe results support the hypothesis that people with persistent neck pain exhibit reduced differential pain-expectancy learning and flatter generalization gradients, reflecting deficits in predictive learning. Contrary to our hypothesis, no differences in extinction were found. These findings may be relevant to understanding behavioral aspects of chronic pain.
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Project description:Noxious cutaneous contact heat stimuli (48 degrees C) are perceived as increasingly painful when the stimulus duration is extended from 5 to 10s, reflecting the temporal summation of central neuronal activity mediating heat pain. However, the sensation of increasing heat pain disappears, reaching a plateau as stimulus duration increases from 10 to 20s. We used functional magnetic resonance imaging (fMRI) in 10 healthy subjects to determine if active central mechanisms could contribute to this psychophysical plateau. During heat pain durations ranging from 5 to 20s, activation intensities in the bilateral orbitofrontal cortices and the activation volume in the left primary (S1) somatosensory cortex correlated only with perceived stimulus intensity and not with stimulus duration. Activation volumes increased with both stimulus duration and perceived intensity in the left lateral thalamus, posterior insula, inferior parietal cortex, and hippocampus. In contrast, during the psychophysical plateau, both the intensity and volume of thalamic and cortical activations in the right medial thalamus, right posterior insula, and left secondary (S2) somatosensory cortex continued to increase with stimulus duration but not with perceived stimulus intensity. Activation volumes in the left medial and right lateral thalamus, and the bilateral mid-anterior cingulate, left orbitofrontal, and right S2 cortices also increased only with stimulus duration. The increased activity of specific thalamic and cortical structures as stimulus duration, but not perceived intensity, increases is consistent with the recruitment of a thalamocortical mechanism that participates in the modulation of pain-related cortical responses and the temporal summation of heat pain.
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Project description:Immersive virtual reality is a powerful method to modify the environment and thereby influence experience. The present study used a virtual hand illusion and context manipulation in immersive virtual reality to examine top-down modulation of pain. Participants received painful heat stimuli on their forearm and placed an embodied virtual hand (co-located with their real one) under a virtual water tap, which dispensed virtual water under different experimental conditions. We aimed to induce a temperature illusion by a red, blue or white light suggesting warm, cold or no virtual water. In addition, the sense of agency was manipulated by allowing participants to have high or low control over the virtual hand's movements. Most participants experienced a thermal sensation in response to the virtual water and associated the blue and red light with cool/cold or warm/hot temperatures, respectively. Importantly, the blue light condition reduced and the red light condition increased pain intensity and unpleasantness, both compared to the control condition. The control manipulation influenced the sense of agency, but did not influence pain ratings. The large effects revealed in our study suggest that context effects within an embodied setting in an immersive virtual environment should be considered within VR based pain therapy.
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