Counterirritation by pain inhibits the responsiveness to aversive loud tones: the role of state anxiety and state fear triggered in the NPU paradigm.

AIM OF THE STUDY: The application of a noxious stimulus reduces the perception and responsiveness to other pain stimuli. This inhibition can be experimentally assessed with a method called 'counterirritation'. The question arises if counterirritation acts also on the perception and responsiveness to aversive but non-nociceptive stimuli (e.g., loud tones). Since aversive stimulation is often associated with state anxiety or state fear, we investigated in addition the modulatory effects of these emotions on counterirritation. MATERIAL AND METHODS: 51 subjects participated in our study. We presented tones with aversive loudness (105 dB), first alone then during counterirritation (immersion of the hand in a hot water bath of 46 °C) to assess inhibition of loudness perception and responsiveness. Influences of state anxiety and state fear on counterirritation were investigated by using the Neutral-Predictable(fear)- Unpredictable(anxiety) Paradigm (NPU), which is based on classical conditioning. Loudness ratings (perception of the aversive tones) and startle reflex (defensive reaction to aversive tones) were assessed. RESULTS: Counterirritation reduced startle reflex amplitudes, but not the loudness ratings. Although state anxiety and state fear were successfully induced, counterirritation remained unaffected. CONCLUSIONS: Our study showed that pain inhibits the responsiveness to aversive stimuli (loud tones). Thus, the postulate that 'pain inhibits pain' might be better changed to 'pain inhibits aversiveness'. Consequently, our findings may also question the assumption of a clear pain specificity in inhibitory action as assumed by theoretical approaches like 'conditioned pain modulation' (CPM). Furthermore, counterirritation appeared one more time resistant to the influence of negative emotions.

Is conditioned pain modulation (CPM) affected by negative emotional state?

BACKGROUND: Conditioned pain modulation (CPM) is an experimental paradigm, which describes the inhibition of responses to a noxious or strong-innocuous stimulus, the test stimulus (TS), by the additional application of a second noxious or strong-innocuous stimulus, the conditioning stimulus (CS). As inadequate CPM efficiency has been assumed to be predisposing for clinical pain, the search for moderating factors explaining inter-individual variations in CPM is ongoing. Psychological factors have received credits in this context. However, research concerning associations between CPM and trait factors relating to negative emotions has yielded disappointing results. Yet, the influence of anxious or fearful states on CPM has not attracted much interest despite ample evidence that negative affective states enhance pain. Our study aimed at investigating the effect of fear induction by symbolic threat on CPM. METHODS: Thirty-seven healthy participants completed two experimental blocks: one presenting aversive pictures showing burn wounds (high-threat block) and one presenting neutral pictures (low-threat block). Both blocks contained a CPM paradigm with contact heat as TS and hot water as CS; subjective numerical ratings as well as contact-heat evoked potentials (CHEPs) were assessed. RESULTS: We detected an overall inhibitory CPM effect for CHEPs amplitudes but not for pain ratings. However, we found no evidence for a modulation of CPM by threat despite threat ratings indicating that our manipulation was successful. DISCUSSION: These results suggest that heat/thermal CPM is resistant to this specific type of symbolic threat induction and further research is necessary to examine whether it is resistant to fearful states in general. SIGNIFICANCE: The attempt of modulating heat conditioned pain modulation (CPM) by emotional threat (fear/anxiety state) failed. Thus, heat CPM inhibition again appeared resistant to emotional influences. Pain-related brain potentials proved to be more sensitive for CPM effects than subjective ratings.

Counterirritation by Pain Inhibits Responses to and Perception of Aversive Loud Tones.

The application of a noxious stimulus reduces the perception of other noxious stimuli, which can be assessed by an experimental method called "counterirritation." The question arises whether this type of inhibition also affects the processing of other aversive (but not nociceptive) stimuli, such as loud tones. If aversiveness or, in other words, negative emotional valence qualifies a stimulus to be affected by counterirritation, the general emotional context may also play a role in modulating counterirritation effects. We involved 63 participants in this study (M age = 38.8, SD = 10.5 years; 33 males, 30 females). We tried to counterirritate their perceptual and startle reactions to aversively loud tones (105 db) by immersing the hand into a painful hot water bath (46°C) in two emotional valence conditions (i.e., a neutral and a negative valence block in which we showed either neutral pictures or pictures of burn wounds). We assessed Inhibition by loudness ratings and startle reflex amplitudes. Counterirritation significantly reduced both loudness ratings and startle reflex amplitudes. The emotional context manipulation did not affect this clear inhibitory effect, showing that counterirritation by a noxious stimulus affects aversive sensations not induced by nociceptive stimuli. Thus, the assumption that "pain inhibits pain" should be widened to "pain inhibits the processing of aversive stimuli." This broadened understanding of counterirritation leads to a questioning of the postulate of clear pain specificity in paradigms like "conditioned pain modulation" (CPM) or "diffuse noxious inhibitory controls" (DNIC).

The induction of social pessimism reduces pain responsiveness.

OBJECTIVES: Past work has found that optimism reduces a person's responsiveness to pain, but the effects of pessimism are not clear. Therefore, we gave pessimistic forecasts of participants' future social life and measured changes in their pain responsiveness. In particular, some participants were told that they would end up alone in life. METHODS: Seventy-five subjects were investigated in three conditions (negative forecast, positive forecast, no forecast) for changes in pain threshold and pain tolerance threshold. Pressure pain induction was accomplished by either human- or machine-driven algometers. A randomly assigned bogus forecast promising either a lonely or a socially satisfying future was ostensibly based on a personality questionnaire and an emotional dot-probe task. As potential covariates, questionnaires assessing dispositional optimism (LOT-R), pain catastrophizing (PCS), and self-esteem (SISE) were given. RESULTS: Pain thresholds suggested a change toward unresponsiveness only in the negative forecast condition, with only small differences between the modes of pain induction (i.e., human or machine). The results for pain tolerance thresholds were less clear also because of limiting stimulation intensity for safety reasons. The covariates were not associated with these changes. CONCLUSIONS: Thus, people expecting a lonely future became moderately less responsive to pain. This numbing effect was not modulated by personality measures, neither in a protective fashion via dispositional optimism and self-esteem nor in a risk-enhancing fashion via trait pain catastrophizing. Alternative mechanisms of action should be explored in future studies.

Attentional processing of pain faces and other emotional faces in chronic pain-an eye-tracking study.

Altered attentional processing of pain-associated stimuli-which might take the form of either avoidance or enhanced vigilance-is thought to be implicated in the development and maintenance of chronic pain. In contrast to reaction time tasks like the dot probe, eye tracking allows for tracking the time course of visual attention and thus differentiating early and late attentional processes. Our study aimed at investigating visual attention to emotional faces in patients with chronic musculoskeletal pain (N = 20) and matched pain-free controls (N = 20). Emotional faces (pain, angry, happy) were presented in pairs with a neutral face for 2000 ms each. Three parameters were determined: First fixation probabilities, fixation durations (overall and divided in four 500 ms intervals) and a fixation bias score as the relative fixation duration of emotional faces compared to neutral faces. There were no group differences in any of the parameters. First fixation probabilities were lower for pain faces than for angry faces. Overall, we found longer fixation duration on emotional compared to neutral faces ('emotionality bias'), which is in accord with previous research. However, significant longer fixation duration compared to the neutral face was detected only for happy and angry but not for pain faces. In addition, fixation durations as well as bias scores yielded evidence for vigilant-avoidant processing of pain faces in both groups. These results suggest that attentional bias towards pain-associated stimuli might not generally differentiate between healthy individuals and chronic pain patients. Exaggerated attentional bias in patients might occur only under specific circumstances, e.g., towards stimulus material specifically relating to the specific pain of the patients under study or under high emotional distress.

Decoding of facial expressions of pain in avatars: does sex matter?

OBJECTIVES: The decoding of facial expressions of pain plays a crucial role in pain diagnostic and clinical decision making. For decoding studies, it is necessary to present facial expressions of pain in a flexible and controllable fashion. Computer models (avatars) of human facial expressions of pain allow for systematically manipulating specific facial features. The aim of the present study was to investigate whether avatars can show realistic facial expressions of pain and how the sex of the avatars influence the decoding of pain by human observers. METHODS: For that purpose, 40 female (mean age: 23.9 years) and 40 male (mean age: 24.6 years) observers watched 80 short videos showing computer-generated avatars, who presented the five clusters of facial expressions of pain (four active and one stoic cluster) identified by Kunz and Lautenbacher (2014). After each clip, observers were asked to provide ratings for the intensity of pain the avatars seem to experience and the certainty of judgement, i.e. if the shown expression truly represents pain. RESULTS: Results show that three of the four active facial clusters were similarly accepted as valid expressions of pain by the observers whereas only one cluster ("raised eyebrows") was disregarded. The sex of the observed avatars influenced the decoding of pain as indicated by increased intensity and elevated certainty ratings for female avatars. CONCLUSIONS: The assumption of different valid facial expressions of pain could be corroborated in avatars, which contradicts the idea of only one uniform pain face. The observers' rating of the avatars' pain was influenced by the avatars' sex, which resembles known observer biases for humans. The use of avatars appeared to be a suitable method in research on the decoding of the facial expression of pain, mirroring closely the known forms of human facial expressions.

Effects of oral alcohol administration on heat pain threshold and ratings of supra-threshold stimuli.

Background and aims Evidence for analgesic effects of oral alcohol consumption on heat pain has recently been documented in a placebo-controlled, randomized and double-blind design. We aimed at further investigating these effects and now set the focus on pain threshold and the ratings of supra-threshold pain to cover most of the pain range. Moreover, we now firstly evaluated sex differences in these effects. Methods We investigated 41 healthy participants (22 females) in a randomized, double-blind and placebo-controlled design and targeted two different moderate breath-alcohol levels of 0.06% and 0.08%. Before and after an alcoholic or placebo drink, contact heat was applied at the forearm. Subjects evaluated pain threshold (method of adjustment) and rated pain intensity and pain unpleasantness of supra-threshold stimuli (intensity: threshold +3 °C; duration: 5 s). Results Analgesic effects taking the form of increased pain thresholds were found after both alcohol doses, surprisingly with more pronounced effects for the lower dose. While the high alcohol dose exerted small analgesic effects on pain intensity ratings (i.e. decrease), slightly increased ratings of pain intensity and pain unpleasantness after the low alcohol dose rather suggest pain enhancement. Alcohol did not affect intensity vs. unpleasantness ratings differentially. We found no evidence for sex differences in any of these effects. Conclusions Overall, acute alcohol effects on pain were subtle. Our findings suggest that while low alcohol doses already exert analgesic effects on pain threshold, stronger doses are required for pain reduction on supra-threshold pain levels. Furthermore, sex differences could not be detected within our experimental paradigm but should be further explored in future research. Implications Analgesic effects of sub-toxic alcohol doses - as normally occurring during social drinking - might be weak; however, susceptibility to pain relieving effects of alcohol might be a risk factor for the use of alcohol as self-medication in acute pain states.

Acute alcohol effects on conditioned pain modulation, but not temporal summation of pain.

Although pain reduction after alcohol administration has repeatedly been demonstrated, alcohol effects on advanced and clinically relevant dynamic pain paradigms are still unknown. As such, temporal summation of pain (TSP) and conditioned pain modulation (CPM) indicate mechanisms of endogenous pain modulation and involve certain neurotransmitter systems crucially influenced by alcohol. Our study is the first to investigate acute alcohol effects on TSP and CPM. We investigated 39 healthy subjects in a placebo-controlled within-subject design and targeted alcohol levels of 0.06% (dose 1) and 0.08% (dose 2). Pain threshold, TSP, and CPM were evaluated before and after an alcoholic or placebo drink. Temporal summation of pain was assessed as enhanced pain response to 5 repetitive contact heat stimuli (threshold +3°C). Conditioned pain modulation was tested as pain inhibition when a conditioning stimulus (46°C hot water) was applied concurrently to a test stimulus (contact heat; threshold + 3°C). Both alcohol doses boosted CPM, with a greater effect size for the higher dose. Conditioning stimulus ratings increased after alcohol intake but were not correlated with CPM, suggesting independence of these effects. Temporal summation of pain was not affected by alcohol, and alcohol effects on pain threshold were small and limited to the higher dose. Our findings suggest that analgesic alcohol effects might be mainly driven by an enhancement of endogenous pain inhibition. The frequent use of alcohol as self-medication in chronic pain might be motivated by alcohol temporarily restoring deficient CPM, thus leading to pain relief in the short run and alcohol-related problems in the long run.

Interactive effects of conditioned pain modulation and temporal summation of pain-the role of stimulus modality.

Conditioned pain modulation (CPM) and temporal summation of pain (TSP) are 2 experimental paradigms capturing endogenous pain modulation, which have repeatedly demonstrated clinical relevance. Conditioned pain modulation describes the inhibition of the pain response to a test stimulus (Ts) when a second noxious stimulus, the conditioning stimulus (CS), is concurrently applied. Temporal summation of pain describes the enhanced pain response to a series of stimuli compared with single stimuli. Temporal summation of pain-limiting effects of CPM are likely but may depend on the stimulus modality of the Ts. This study aimed at investigating these differential effects of stimulus modality. Thirty-five healthy volunteers completed 2 experimental blocks (Ts modality: pressure vs heat) in balanced order. Both blocks consisted of 3 conditions: baseline (no CS), CPM1 (nonpainful CS: 42°C water bath), and CPM2 (painful CS: 46°C water bath). Single stimuli and series of stimuli were alternatingly applied to assess TSP by means of a Numerical Rating Scale. Both TSP and CPM were successfully induced with no difference between the 2 Ts modalities. We also detected a significant interaction between TSP and CPM, with higher pain reduction for a series of Ts compared with single Ts during the painful CS. Interestingly, this interaction was modality-dependent: TSP for heat Ts was completely abolished by CPM, whereas this was not the case for pressure Ts. Our findings suggest different forms of central sensitization induced by TSP using either heat or pressure stimuli, which differ in their susceptibility to CPM. Clinical implications and directions for future research are discussed.

Associations of nocturnal sleep with experimental pain and pain catastrophizing in healthy volunteers.

Strong alterations of night sleep (e.g., sleep deprivation, insomnia) have appeared to affect pain in inducing hyperalgesic changes. However, it has remained unclear whether everyday variations of night sleep in healthy individuals have any influence on pain processing. Forty healthy subjects were studied by portable polysomnography (PSG) and sleep questionnaire during two non-consecutive nights at home. Experimental pain parameters (pressure pain threshold, temporal summation = TS, conditioned pain modulation = CPM) and situational pain catastrophizing (Situational Catastrophizing Questionnaire = SCQ) were always assessed the evening before and the morning after sleep recording in a pain laboratory. Linear regression analyses were computed to test the prediction of overnight changes in pain by different sleep parameters. Significant prediction of changes in pain parameters by sleep parameters was limited (2 out of 12 analyses), indicating that everyday variations in sleep under non-pathological and low stress conditions are only weakly associated with pain.

The Relationship Between Pain Severity and Alcohol Use Among School-Aged Children and Adolescents: The Moderating Role of Drinking Motives.

Objective: Evidence from adult samples suggests a co-occurrence between pain and alcohol abuse. However, studies in adolescents are scarce and results are inconsistent, with some studies observing heightened and others observing reduced alcohol consumption in adolescents suffering from pain. We hypothesized that in adolescents the association between pain and alcohol use will be moderated by drinking motives. Methods: Data from a large representative sample of Flemish school children and adolescents (N = 10,650, 50.8% boys, age range = 10-21 years, Mage = 14.33 years) were collected as part of the World Health Organization collaborative Health Behaviour in School-Aged Children (HBSC) survey. Pain severity was graded based on a pediatric pain classification system that accounts for both pain intensity and disability. Alcohol consumption was operationalized using two variables: frequency of drinking and drunkenness. The Drinking Motives Questionnaire-Revised was used to capture drinking motives; it assesses four motive categories (enhancement, coping, social, and conformity). Results: Findings indicated that higher pain severity was associated with greater frequency of alcohol use and drunkenness. However, drinking motives moderated this association. The positive association between pain severity and drinking frequency was stronger in case of high conformity motives. Likewise, the association between pain severity and drunkenness frequency was stronger at high levels of conformity motives and reached significance only at high levels of coping motives. Conclusions: Our findings suggest that specific drinking motives are linked to problematic alcohol use in adolescents with pain. Future studies using a longitudinal design are needed to draw conclusions about direction of effects.

Acute alcohol effects on facial expressions of emotions in social drinkers: a systematic review.

BACKGROUND: As known from everyday experience and experimental research, alcohol modulates emotions. Particularly regarding social interaction, the effects of alcohol on the facial expression of emotion might be of relevance. However, these effects have not been systematically studied. We performed a systematic review on acute alcohol effects on social drinkers' facial expressions of induced positive and negative emotions. MATERIALS AND METHODS: With a predefined algorithm, we searched three electronic databases (PubMed, PsycInfo, and Web of Science) for studies conducted on social drinkers that used acute alcohol administration, emotion induction, and standardized methods to record facial expressions. We excluded those studies that failed common quality standards, and finally selected 13 investigations for this review. RESULTS: Overall, alcohol exerted effects on facial expressions of emotions in social drinkers. These effects were not generally disinhibiting, but varied depending on the valence of emotion and on social interaction. Being consumed within social groups, alcohol mostly influenced facial expressions of emotions in a socially desirable way, thus underscoring the view of alcohol as social lubricant. However, methodical differences regarding alcohol administration between the studies complicated comparability. CONCLUSION: Our review highlighted the relevance of emotional valence and social-context factors for acute alcohol effects on social drinkers' facial expressions of emotions. Future research should investigate how these alcohol effects influence the development of problematic drinking behavior in social drinkers.

Psychological Predictors of Acute Postoperative Pain After Hysterectomy for Benign Causes.

OBJECTIVES: Psychological parameters have been shown to contribute significantly to the development of acute postoperative pain (APOP). For the prediction of APOP in chest malformation patients and cancer patients, we found pain-specific psychological predictors to be of higher relevance than general psychological predictors. The current study aims to further substantiate these findings. MATERIALS AND METHODS: In a sample of 73 middle-aged hysterectomy patients, 3 predictor sets were assessed 1 day before surgery: attentional biases (toward pain-related, social threat, and positive words in a dot-probe task), pain-related emotions and cognitions (pain anxiety, pain catastrophizing, and pain hypervigilance), and affective state variables (depression and somatization). APOP intensity rated 2 to 3 days after surgery and analgesic consumption during the first 48 postoperative hours were used as outcome measures. RESULTS: APOP intensity ratings were significantly explained by their best single predictors in a multiple regression analysis: social threat words of the dot-probe task, pain anxiety, and somatization (14.7% of explained variance). When comparing standardized ß coefficients, pain-specific psychological predictors appeared to be of higher explanatory relevance than general psychological predictors. In contrast, analgesic consumption could not be significantly predicted by the psychological variables. DISCUSSION: Hysterectomy patients at risk for high APOP intensity could be characterized by the psychological variables used, whereas their predictive value for analgesic consumption was limited. The high predictive potency of pain-specific psychological variables should be considered for further improvement of pain management and prevention, because pain-specific variables such as pain anxiety can be the target of focal psychological interventions when preparing for surgery.

Lack of predictive power of trait fear and anxiety for conditioned pain modulation (CPM).

In recent years the association of conditioned pain modulation (CPM) with trait fear and anxiety has become a hot topic in pain research due to the assumption that such variables may explain the low CPM efficiency in some individuals. However, empirical evidence concerning this association is still equivocal. Our study is the first to investigate the predictive power of fear and anxiety for CPM by using a well-established psycho-physiological measure of trait fear, i.e. startle potentiation, in addition to two self-report measures of pain-related trait anxiety. Forty healthy, pain-free participants (female: N = 20; age: M = 23.62 years) underwent two experimental blocks in counter-balanced order: (1) a startle paradigm with affective picture presentation and (2) a CPM procedure with hot water as conditioning stimulus (CS) and contact heat as test stimulus (TS). At the end of the experimental session, pain catastrophizing (PCS) and pain anxiety (PASS) were assessed. PCS score, PASS score and startle potentiation to threatening pictures were entered as predictors in a linear regression model with CPM magnitude as criterion. We were able to show an inhibitory CPM effect in our sample: pain ratings of the heat stimuli were significantly reduced during hot water immersion. However, CPM was neither predicted by self-report of pain-related anxiety nor by startle potentiation as psycho-physiological measure of trait fear. These results corroborate previous negative findings concerning the association between trait fear/anxiety and CPM efficiency and suggest that shifting the focus from trait to state measures might be promising.

The effect of nonrecurring alcohol administration on pain perception in humans: a systematic review.

PURPOSE: Alcohol is believed to have pain-dampening effects and is often used as self-medication by persons with pain problems; however, experimental evidence confirming this effect is scarce. We conducted a systematic review of experimental studies on the effects of nonrecurring alcohol administration on pain perception in healthy human subjects and the underlying mechanisms. METHOD: Three databases (PubMed, PsycINFO, and Web of Science) were searched for relevant studies using a predefined algorithm. In a next step, irrelevant articles were excluded by screening titles and abstracts. Finally, articles were checked regarding a set of methodological criteria; only publications meeting these criteria were selected for this review. A total of 14 experimental studies were identified. RESULTS: Overall, most of the studies were able to show a pain-dampening effect of alcohol. However, many of them had methodological shortcomings (eg, lack of placebo control, insufficient blinding, or very small sample sizes). In addition, comparability is limited due to considerable variations in alcohol administration and pain measurement. More importantly, potential mechanisms of action and moderating variables have scarcely been investigated. CONCLUSION: Despite the frequent use of alcohol as self-medication by persons with pain problems, there are to date only a few experimental investigations of alcohol effects on pain perceptions. The results of these studies suggest that alcohol does in fact have pain-dampening effects. However, the mechanisms implicated in these effects are still unknown, and experimental research has been limited to pain-free subjects. Future research should provide more knowledge about alcohol effects on pain, especially in chronic pain patients.