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PAIN 155 (2014) 2033–2039
www.elsevier.com/locate/pain
Attention effects on vicarious modulation of nociception and pain Ali Khatibi a,⇑, Etienne Vachon-Presseau b,c, Martien Schrooten a,d, Johan Vlaeyen a,e, Pierre Rainville b,f,g a
Research Group on Health Psychology, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium Departement de Psychologie, Université de Montréal, Montréal, Quebec, Canada c Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montréal, Quebec, Canada d Center for Health and Medical Psychology, Örebro University, Örebro, Sweden e Department of Clinical Psychological Science, Maastricht University, Maastricht, The Netherlands f Department of Stomatology, Faculty of Dentistry, Université de Montréal, Montréal, Quebec, Canada g Groupe de Recherche sur le Systeme Nerveux Central (GRSNC), Université de Montréal, Montréal, Quebec, Canada b
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
a r t i c l e
i n f o
Article history: Received 30 October 2013 Received in revised form 27 June 2014 Accepted 3 July 2014
Keywords: Attentional modulation Facial expression of pain Nociceptive flexion reflex Pain perception Vicarious facilitation
a b s t r a c t The observation of others’ facial expressions of pain has been shown to facilitate the observer’s nociceptive responses and to increase pain perception. We investigated how this vicarious facilitation effect is modulated by directing the observer’s attention toward the meaning of pain expression or the facial movements. In separate trials, participants were instructed to assess the ‘‘intensity of the pain expression’’(meaning) or to ‘‘discriminate the facial movements’’ in the upper vs lower part of the face shown in 1-second dynamic clips displaying mild, moderate, or strong pain expressions or a neutral control. In 50% of the trials, participants received a painful electrical stimulation to the sural nerve immediately after the presentation of the expression. Low-level nociceptive reactivity was measured with the RIII-response, and pain perception was assessed using pain ratings. Pain induced by the electrical stimulation increased after viewing stronger pain expressions in both tasks, but the RIII-response showed this vicarious facilitation effect only in the movement discrimination task at the strongest expression intensity. These findings are consistent with the notion that vicarious processes facilitate self-pain and may prime automatic nociceptive responses. However, this priming effect is influenced by top-down attentional processes. These results provide another case of dissociation between reflexive and perceptual processes, consistent with the involvement of partly separate brain networks in the regulation of cortical and lower-level nociceptive responses. Combined with previous results, these findings suggest that vicarious pain facilitation is an automatic process that may be diminished by top-down attentional processes directed at the meaning of the expression. Ó 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
1. Introduction Facial expressions are communication channels by which people inform others about their feelings and state [15]. Facial expressions of pain provide vital information about the presence of threat in the environment, increasing alertness about occurrence of danger and improving the efficacy of defensive reaction [13,34,40]. In addition to improving self-protective responses, observation of
⇑ Corresponding author. Address: Laboratory of Research on Neuropsychology of Pain, Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal (CRIUGM), 4545, Chemin Queen-Mary Montréal, Québec H3W 1W4, Canada. Tel.: +1 (514) 340 3540x2835; fax: +1 (514) 340 3530. E-mail address: [email protected] (A. Khatibi).
pain in another person can elicit empathic responses that may encourage altruistic behavior of the observer toward the person in pain [22]. The current study sought to further examine how attention to the level of pain, rather than to movements, in expressions primes observers’ pain systems. Brain imaging studies have shown that observation of others’ pain expressions activates brain areas associated with the human mirror neuron system, the affective processing of pain, and in the theory of mind [7,33]. Budell et al. showed that attention to the level of pain in expressions is associated with stronger activation in brain areas associated with the extraction of meaning from expressions (ie, ventral-inferior-frontal gyrus and medialprefrontal cortex), whereas attention to facial movements is associated with greater activation in movement-related brain areas
http://dx.doi.org/10.1016/j.pain.2014.07.005 0304-3959/Ó 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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(eg, inferior-parietal lobule and premotor cortex). This research suggested that processing of pain in others’ expressions recruits regions involved in the affective coding of pain and motor mirroring and demonstrated that the relative engagement of different parts of these networks is under the influence of top-down mechanisms. Consistent with the perception-action model of empathy [22], previous studies showed that the passive viewing of pain expressions immediately before the delivery of painful electrical stimuli increases pain ratings [19,32]. Moreover, observation of dynamic pain expressions produces a facilitation of the nociceptive flexion reflex (NFR) [19], an automatic withdrawal response generated by spinal nociceptive circuits [29]. These effects demonstrate a vicarious facilitation of pain-related processes involving the priming of defensive/protective responses and reflecting a fundamental adaptive function of pain communication. Unexpectedly, this vicarious facilitation effect was lower in individuals with higher levels of dispositional empathy [19,32]. This may reflect a self/ other bias with attention resources spontaneously directed more strongly toward the other person’s suffering in highly empathic individuals, resulting in less vicarious facilitation, and toward the self in low empathic individuals, resulting in more vicarious facilitation. These individual biases were observed in conditions involving the passive viewing of pain faces and may be strongly dependent on task demands. This study investigated the effect of attentional modulation on the vicarious facilitation of responses to pain. We compared pain ratings and RIII reflexes induced by electrical stimuli when participants attended to the amount of pain in facial displays as compared with when they attended to the facial movements [7]. We hypothesized that the explicit processing of a pain expression would enhance vicarious pain effects through a generalized priming of self-pain responses (ie, pain resonance effect). However, based on nonspecific motor priming processes, we also considered the alternative possibility that attention to motor features of pain expression might facilitate the NFR (ie, motor priming effect). Finally, based on the effects of dispositional empathy previously observed (ie, self/other attention bias), we considered the possibility that attention directed at the meaning of pain expressions might reduce vicarious facilitation effects. 2. Methods 2.1. Participants Thirty-three healthy English-speaking individuals were recruited through advertisements posted in public places (research center and university) and on social websites. Exclusion criteria were verified in the recruitment process and at the beginning of the testing session, and included a history of chronic pain, neurological problems, and current pain before the test. Participants were asked not to take analgesics 24 hours before testing. One participant was removed from analyses after the testing session when he indicated that he had omitted to report the presence of musculoskeletal pain before and during the test session. The remaining 32 participants (16 female) had a mean ± SD age of 25.8 ± 6.1 years (range 18 to 45). The study was approved by the ethics committee of the Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal (CRIUGM; CMER-RNQ_12-13-08). 2.2. Electrocutaneous stimulation and NFR The NFR was elicited by a series of 10 square-wave electrical stimuli (1-ms stimulus duration and 2-ms interstimulus interval, resulting in a total stimulation duration of 30 ms) at the distal end of the sural nerve. Stimulation was applied to the retromalleolar site
(cathode proximal) of the sural nerve using two 1-cm bipolar surface electrodes. Muscle reflex activity (RIII reflex) was recorded from the brevis head of the ipsilateral biceps femoris muscle using 2 recording electrodes (EL503, BIOPAC; interelectrode distance 4 cm) placed on the previously cleaned, shaved (if necessary), and abraded skin in order to reach an impedance of .9); there was, however, a significant interaction between task type and pain expression level (F(3,93) = 3.8, P = .01, g2p = 0.11). Planned pairwise comparisons revealed that during the pain expression evaluation task there was no significant difference between 4 levels of expressions, Ps > .07, whereas during the facial movement discrimination task, NFR was significantly higher in the trials with strong pain expressions than neutral, mild pain, and moderate pain expressions (all Ps < .01). For significant main effect of expression, a linear trend provided the best fit (F(1,31) = 18.5, P < .001). Direct comparison of NFR response between tasks also confirmed the stronger NFR in the movement task as compared with the pain expression task for the strong pain facial expression condition (t(31) = 2.12, P = .04, Cohen’s d = 0.37). Together, these results reveal that viewing higher pain expression levels facilitated the NFR response induced by the electrical stimulation when attention is directed at the facial movements (Fig 2). 3.4. Experienced pain ratings Fig. 3 shows an overview of participants’ pain ratings (z scores) in 2 tasks for 4 levels of pain expression. The repeated-measures ANOVA on participants’ ratings z-scores showed a significant main effect of pain expression level (F(3,93) = 11.8, P < .001, g2p = 0.28). Planned pairwise comparisons revealed that participants’ ratings of electrical stimulation pain in the trials with strong pain expression was significantly higher than their rating of electrical stimulation pain in the trials with neutral expression (P = .01; 0.08 < 95% CI < 0.91), and mild pain expression (P = .001; 0.16 < 95% CI < 0.78), but not significantly different from moderate pain (P = .15; 0.04 < 95% CI < 0.45). In addition, participants’ rating of electrical stimulation pain in the trials with moderate pain expression were significantly higher than trials with mild pain expression (P < .001; 0.12 < 95% CI < 0.41). This significant main effect of the level of expression fitted with a linear trend (F(1,31) = 14.2, P = .001). The main effect of task type and the interaction between task type and level of pain expression were not significant (Fs < 0.83, Ps > .4). These findings indicate that the pain ratings were increased by observation of stronger expressions, and this
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Fig. 3. Mean (SEM) standardized pain ratings (z-score) as a function of task and intensity of the pain expression shown. Results show a main effect of pain expression levels but did not confirm a crossover interaction between task type and pain expression level (see statistical results in Section 3.3).
was independent from the pain evaluation and the movement discrimination conditions. 3.5. Correlations between modulation of responses to pain and empathy A Pearson correlation between facilitation of responses in the trials with strong pain expression (vs neutral) and dispositional empathy (EQ) revealed no significant or close to significant correlation in either task (all rs < .2 and Ps > .2). 4. Discussion 4.1. Vicarious facilitation of responses to painful stimulus In our study, observation of stronger expressions was followed by stronger responses to painful stimulus at both reflexive and perceptual levels. These are in line with previously observed vicarious facilitation of responses to painful stimuli [19,32]. Different mechanisms are suggested to be involved in the vicarious facilitation of responses to painful stimuli. Some studies showed that manipulation of individuals’ emotional status, through priming by negative stimuli (eg, International Affective Picture System, sad music) can influence their responses to pain, with negative mood manipulation resulting in higher NFR and pain ratings [24,27,35]. Rhudy et al. [22] further suggested that the valence of a stimulus explains the direction of the pain modulation, whereas its arousal predicts the amplitude of the modulation. However, singular involvement of emotional factors has been questioned by the findings of a previous study that showed that among emotional arousing stimuli with negative valence, those with pain-related contents are most effective to modulate pain in observers [14]. Additionally, Roy et al. showed that pain expressions are generally rated low on arousal but facilitate pain comparable to studies relying on highly arousing negative pictures [25]. A recent study compared the effect of pain, fear, and joy expressions on heat pain perception and found that only the pain expression produced pain modulation compared with neutral faces [21]. The findings of this study and previous studies suggest that pain-related information, in comparison with emotion-related characteristics, play a more important role in the vicarious modulation of individuals’ responses to pain.
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Aside from the suggestion about the role of emotional factors in the vicarious pain modulation, some studies proposed that a sensorimotor resonance between the communicated pain signal in others (eg, facial expression) and observers’ neural systems may prime responses to pain in observers and might result in increased reactivity to acute pain stimuli. These studies rely on the perceptionaction model, which suggests that, similar to actions, perception of another person’s emotional state occurs through a corresponding activation in the observer’s brain that represents firsthand experience of that emotion [22]. This is supported by studies showing partial overlap between brain activation observed during the perception of pain in others and that associated with the firsthand experience of pain [16,17]. In this context, the observed vicarious facilitation of pain may be explained by the activation of brain areas responsible for the processing of self-pain as the result of resonance with cues signaling pain in others. In addition, previous studies have shown that a higher level of dispositional empathy in the observer is associated with less facilitation of responses to painful stimuli [19,32]. They assumed stronger empathy is associated with attention driven away from experienced pain, which can result in lower pain ratings [20]. However, in our study we failed to replicate those findings, possibly because all participants were instructed to actively attend toward the expressions. 4.2. Neurocognitive modulation of the vicarious facilitation of spinal and supraspinal responses The processing of the movement of a pain expression seems to play an important role in the vicarious modulation of the NFR. It has been shown that viewing dynamic as compared to static expressions results in greater neural activation in the brain of the observer [30]. Consistent with this, the vicarious facilitation of the NFR was previously found in response to passive viewing of dynamic [19] but not static expressions [25,32]. In the present study, the NFR was facilitated by observation of pain expressions with higher levels of pain in the movement rating trials than in the pain rating trials. This implies that stimulus-driven effects induced by dynamic expressions on spinal processes may be inhibited when attention is directed toward higher-order processing of the meaning of the expression. Modulation of corticospinal activity by vicarious pain also has been shown in studies using transcranial magnetic stimulation of the motor cortex. For example, observation of images showing the stimulation of the hand of another person with a needle inhibited the motor evoked potentials by transcranial magnetic stimulation of the observer’s motor cortex for the congruent hand [3] and facilitated the motor evoked potentials for the incongruent hand [4]. The observed inhibition could reflect a reduced sensitivity of the motor cortex involved in a somatotopically specific resonance process, whereas the facilitation at the contralateral hand might be indicative of a generalized vicarious facilitation effect in favor of escape behaviors. Pain expressions do not carry information about spatial properties of the pain of the observed person, so they might produce similar general facilitation of motor defensive responses. A study with the same task used in the current study showed that attention toward dynamic aspects of expressions is associated with a significant increase in blood oxygen level dependent (BOLD) signal in the inferior parietal lobule (IPL) and the premotor areas [7] in comparison with attention toward pain, associated with significantly increased activation in different areas of the brain (eg, medial prefrontal cortex (mPFC)). Modulation of activity in the premotor cortex, which is suggested to be associated with change in corticospinal excitability (eg, inferred from disruption of motor facilitation after action observation) [1,2], may result in diffuse motor priming and increased spinal reflexes via descending facilitation [33]. Aside
from this, several studies have shown that observation of others’ pain is associated with activation in insula, anterior-cingulate cortex, and the supplementary motor area [16,17,28]. These regions may also be involved in moderating the effects of emotion and competing sustained pain on acute self-pain and spinal responses via change in activation of paracentral lobule [21,27] and could have a role in the modulation of the NFR by pain observation. Further investigations are needed to explore how brain regions involved in the perception of pain in others might contribute to vicarious facilitation of spinal nociception and self-pain. 4.3. Differential attention modulation of vicarious pain responses at perceptual and reflexive levels The observed difference between pain ratings (perceptual processing) and the NFR (spinal-nociceptive processing) in attentional effects on vicarious facilitation suggests that separate networks are involved in these 2 modulatory processes. This is in accordance with findings of a number of previous studies clearly showing dissociations between pain-related perceptual and spinal responses [12,26,32]. The multidimensional approach to studying empathy differentiates at least 2 levels in the processing of pain in others [9,11,22]. At the early stage, low-level responses are indicative of involvement of fast and automatic mechanisms subserving alerting and defensive functions. At the later stage, higher-order processing contributes to the self-regulatory mechanisms in the observer in the context of pain communication, which can influence pain perception. The low-level responses can be modulated by descending signals from higher-order structures in the brain. The NFR, as a reflexive low-level response, can be inhibited/facilitated by supraspinal signals (eg, during hypnosis or anticipation of pain) [10,37]. Attention toward the affective dimension of pain in the expression may block the facilitation at the spinal level. One possible mechanism of this modulation is the involvement of prefrontal regions, which have been shown to be activated by attention toward the meaning of dynamic pain expressions [7] and are also involved in the expectation-induced analgesia [36]. Admittedly, this interpretation is speculative and calls for further investigation. 4.4. Limitations and future directions Stimuli included in the current study were only neutral or pain expressions. Inclusion of other types of negative/positive expressions may help to further tease apart nonspecific effects of arousal and valence on spinal nociception [22]. However, 3 studies suggest that these nonspecific emotional dimensions seem insufficient to explain vicarious pain effects [14,23,25]. The present study also did not include a passive observation condition, and we relied on a comparison with our previous studies to interpret the effects of the 2 task conditions. Aside from that, the paradigm did not allow us to assess task demands and their influence on subjects’ responses. It is possible that when observing pain expressions, evaluation of pain intensity is a more natural and automatic task, whereas comparison of movement between different face parts is more attention demanding. However, in this case we would expect to see analgesic effects of distraction (ie, reduced pain responses in the movement task as compared with the pain task) [5,20]. This was, however, not the case here. In addition, perceived social distance could potentially influence responsiveness to emotion in others’ facial expressions [18]; future studies might manipulate (or control) perceived social distance and investigate its influence on vicarious pain responses. Finally, future studies may investigate brain correlates of the attentional modulation of vicarious facilitations and test some of the admittedly speculative hypotheses proposed earlier.
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4.5. Conclusions Communication of pain is influenced by contextual and psychological factors affecting the observers, which may in turn influence their own behavioral, affective, or cognitive reactions to pain [15]. In our study, modulation of observers’ attention toward superficial aspects of pain expressions (movements) or toward the meaning of these expressions resulted in a dissociation between a low-level defensive responses and higher-order processes underlying pain perception. The facilitation of the withdrawal responses seemed to be blocked by the engagement of higher-order processes subserving the extraction of meaning. In line with the perception-action model and previous work showing multiple-level processing of empathic signals, these findings further suggest that vicarious processes rely on at least partly separable networks underlying the cortical processing of pain signals and the descending modulation of pain-related responses. These findings help us to better understand the cognitive mechanisms involved in the communication of pain-related signals. Conflict of interest statement The authors declare no conflict of interest. Acknowledgments
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[13] [14]
[15]
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[18]
[19]
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The authors thank Veronique Taylor for her help during data acquisition. This research was funded by a grant to Pierre Rainville from the National Science Research Council of Canada (NSERC; no. 341472-07/2013). Ali Khatibi was supported by an award from junior mobility program (JuMo) from KU Leuven. Pierre Rainville and Etienne Vachon-Presseau were supported by the Fonds de la recherche Québec–Santé and the Canadian Institutes of Health Research (CIHR), respectively. The contribution of Johan Vlaeyen and Martien Schrooten was supported by the Odysseus Grant ‘‘the Psychology of Pain and Disability Research Program’’ funded by the Research Foundation–Flanders (FWO Vlaanderen, Belgium). Appendix A. Supplementary data
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Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.pain.2014.07.005.
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PAIN 155 (2014) 2033–2039
www.elsevier.com/locate/pain
Attention effects on vicarious modulation of nociception and pain Ali Khatibi a,⇑, Etienne Vachon-Presseau b,c, Martien Schrooten a,d, Johan Vlaeyen a,e, Pierre Rainville b,f,g a
Research Group on Health Psychology, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium Departement de Psychologie, Université de Montréal, Montréal, Quebec, Canada c Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montréal, Quebec, Canada d Center for Health and Medical Psychology, Örebro University, Örebro, Sweden e Department of Clinical Psychological Science, Maastricht University, Maastricht, The Netherlands f Department of Stomatology, Faculty of Dentistry, Université de Montréal, Montréal, Quebec, Canada g Groupe de Recherche sur le Systeme Nerveux Central (GRSNC), Université de Montréal, Montréal, Quebec, Canada b
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
a r t i c l e
i n f o
Article history: Received 30 October 2013 Received in revised form 27 June 2014 Accepted 3 July 2014
Keywords: Attentional modulation Facial expression of pain Nociceptive flexion reflex Pain perception Vicarious facilitation
a b s t r a c t The observation of others’ facial expressions of pain has been shown to facilitate the observer’s nociceptive responses and to increase pain perception. We investigated how this vicarious facilitation effect is modulated by directing the observer’s attention toward the meaning of pain expression or the facial movements. In separate trials, participants were instructed to assess the ‘‘intensity of the pain expression’’(meaning) or to ‘‘discriminate the facial movements’’ in the upper vs lower part of the face shown in 1-second dynamic clips displaying mild, moderate, or strong pain expressions or a neutral control. In 50% of the trials, participants received a painful electrical stimulation to the sural nerve immediately after the presentation of the expression. Low-level nociceptive reactivity was measured with the RIII-response, and pain perception was assessed using pain ratings. Pain induced by the electrical stimulation increased after viewing stronger pain expressions in both tasks, but the RIII-response showed this vicarious facilitation effect only in the movement discrimination task at the strongest expression intensity. These findings are consistent with the notion that vicarious processes facilitate self-pain and may prime automatic nociceptive responses. However, this priming effect is influenced by top-down attentional processes. These results provide another case of dissociation between reflexive and perceptual processes, consistent with the involvement of partly separate brain networks in the regulation of cortical and lower-level nociceptive responses. Combined with previous results, these findings suggest that vicarious pain facilitation is an automatic process that may be diminished by top-down attentional processes directed at the meaning of the expression. Ó 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
1. Introduction Facial expressions are communication channels by which people inform others about their feelings and state [15]. Facial expressions of pain provide vital information about the presence of threat in the environment, increasing alertness about occurrence of danger and improving the efficacy of defensive reaction [13,34,40]. In addition to improving self-protective responses, observation of
⇑ Corresponding author. Address: Laboratory of Research on Neuropsychology of Pain, Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal (CRIUGM), 4545, Chemin Queen-Mary Montréal, Québec H3W 1W4, Canada. Tel.: +1 (514) 340 3540x2835; fax: +1 (514) 340 3530. E-mail address: [email protected] (A. Khatibi).
pain in another person can elicit empathic responses that may encourage altruistic behavior of the observer toward the person in pain [22]. The current study sought to further examine how attention to the level of pain, rather than to movements, in expressions primes observers’ pain systems. Brain imaging studies have shown that observation of others’ pain expressions activates brain areas associated with the human mirror neuron system, the affective processing of pain, and in the theory of mind [7,33]. Budell et al. showed that attention to the level of pain in expressions is associated with stronger activation in brain areas associated with the extraction of meaning from expressions (ie, ventral-inferior-frontal gyrus and medialprefrontal cortex), whereas attention to facial movements is associated with greater activation in movement-related brain areas
http://dx.doi.org/10.1016/j.pain.2014.07.005 0304-3959/Ó 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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(eg, inferior-parietal lobule and premotor cortex). This research suggested that processing of pain in others’ expressions recruits regions involved in the affective coding of pain and motor mirroring and demonstrated that the relative engagement of different parts of these networks is under the influence of top-down mechanisms. Consistent with the perception-action model of empathy [22], previous studies showed that the passive viewing of pain expressions immediately before the delivery of painful electrical stimuli increases pain ratings [19,32]. Moreover, observation of dynamic pain expressions produces a facilitation of the nociceptive flexion reflex (NFR) [19], an automatic withdrawal response generated by spinal nociceptive circuits [29]. These effects demonstrate a vicarious facilitation of pain-related processes involving the priming of defensive/protective responses and reflecting a fundamental adaptive function of pain communication. Unexpectedly, this vicarious facilitation effect was lower in individuals with higher levels of dispositional empathy [19,32]. This may reflect a self/ other bias with attention resources spontaneously directed more strongly toward the other person’s suffering in highly empathic individuals, resulting in less vicarious facilitation, and toward the self in low empathic individuals, resulting in more vicarious facilitation. These individual biases were observed in conditions involving the passive viewing of pain faces and may be strongly dependent on task demands. This study investigated the effect of attentional modulation on the vicarious facilitation of responses to pain. We compared pain ratings and RIII reflexes induced by electrical stimuli when participants attended to the amount of pain in facial displays as compared with when they attended to the facial movements [7]. We hypothesized that the explicit processing of a pain expression would enhance vicarious pain effects through a generalized priming of self-pain responses (ie, pain resonance effect). However, based on nonspecific motor priming processes, we also considered the alternative possibility that attention to motor features of pain expression might facilitate the NFR (ie, motor priming effect). Finally, based on the effects of dispositional empathy previously observed (ie, self/other attention bias), we considered the possibility that attention directed at the meaning of pain expressions might reduce vicarious facilitation effects. 2. Methods 2.1. Participants Thirty-three healthy English-speaking individuals were recruited through advertisements posted in public places (research center and university) and on social websites. Exclusion criteria were verified in the recruitment process and at the beginning of the testing session, and included a history of chronic pain, neurological problems, and current pain before the test. Participants were asked not to take analgesics 24 hours before testing. One participant was removed from analyses after the testing session when he indicated that he had omitted to report the presence of musculoskeletal pain before and during the test session. The remaining 32 participants (16 female) had a mean ± SD age of 25.8 ± 6.1 years (range 18 to 45). The study was approved by the ethics committee of the Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal (CRIUGM; CMER-RNQ_12-13-08). 2.2. Electrocutaneous stimulation and NFR The NFR was elicited by a series of 10 square-wave electrical stimuli (1-ms stimulus duration and 2-ms interstimulus interval, resulting in a total stimulation duration of 30 ms) at the distal end of the sural nerve. Stimulation was applied to the retromalleolar site
(cathode proximal) of the sural nerve using two 1-cm bipolar surface electrodes. Muscle reflex activity (RIII reflex) was recorded from the brevis head of the ipsilateral biceps femoris muscle using 2 recording electrodes (EL503, BIOPAC; interelectrode distance 4 cm) placed on the previously cleaned, shaved (if necessary), and abraded skin in order to reach an impedance of .9); there was, however, a significant interaction between task type and pain expression level (F(3,93) = 3.8, P = .01, g2p = 0.11). Planned pairwise comparisons revealed that during the pain expression evaluation task there was no significant difference between 4 levels of expressions, Ps > .07, whereas during the facial movement discrimination task, NFR was significantly higher in the trials with strong pain expressions than neutral, mild pain, and moderate pain expressions (all Ps < .01). For significant main effect of expression, a linear trend provided the best fit (F(1,31) = 18.5, P < .001). Direct comparison of NFR response between tasks also confirmed the stronger NFR in the movement task as compared with the pain expression task for the strong pain facial expression condition (t(31) = 2.12, P = .04, Cohen’s d = 0.37). Together, these results reveal that viewing higher pain expression levels facilitated the NFR response induced by the electrical stimulation when attention is directed at the facial movements (Fig 2). 3.4. Experienced pain ratings Fig. 3 shows an overview of participants’ pain ratings (z scores) in 2 tasks for 4 levels of pain expression. The repeated-measures ANOVA on participants’ ratings z-scores showed a significant main effect of pain expression level (F(3,93) = 11.8, P < .001, g2p = 0.28). Planned pairwise comparisons revealed that participants’ ratings of electrical stimulation pain in the trials with strong pain expression was significantly higher than their rating of electrical stimulation pain in the trials with neutral expression (P = .01; 0.08 < 95% CI < 0.91), and mild pain expression (P = .001; 0.16 < 95% CI < 0.78), but not significantly different from moderate pain (P = .15; 0.04 < 95% CI < 0.45). In addition, participants’ rating of electrical stimulation pain in the trials with moderate pain expression were significantly higher than trials with mild pain expression (P < .001; 0.12 < 95% CI < 0.41). This significant main effect of the level of expression fitted with a linear trend (F(1,31) = 14.2, P = .001). The main effect of task type and the interaction between task type and level of pain expression were not significant (Fs < 0.83, Ps > .4). These findings indicate that the pain ratings were increased by observation of stronger expressions, and this
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Fig. 3. Mean (SEM) standardized pain ratings (z-score) as a function of task and intensity of the pain expression shown. Results show a main effect of pain expression levels but did not confirm a crossover interaction between task type and pain expression level (see statistical results in Section 3.3).
was independent from the pain evaluation and the movement discrimination conditions. 3.5. Correlations between modulation of responses to pain and empathy A Pearson correlation between facilitation of responses in the trials with strong pain expression (vs neutral) and dispositional empathy (EQ) revealed no significant or close to significant correlation in either task (all rs < .2 and Ps > .2). 4. Discussion 4.1. Vicarious facilitation of responses to painful stimulus In our study, observation of stronger expressions was followed by stronger responses to painful stimulus at both reflexive and perceptual levels. These are in line with previously observed vicarious facilitation of responses to painful stimuli [19,32]. Different mechanisms are suggested to be involved in the vicarious facilitation of responses to painful stimuli. Some studies showed that manipulation of individuals’ emotional status, through priming by negative stimuli (eg, International Affective Picture System, sad music) can influence their responses to pain, with negative mood manipulation resulting in higher NFR and pain ratings [24,27,35]. Rhudy et al. [22] further suggested that the valence of a stimulus explains the direction of the pain modulation, whereas its arousal predicts the amplitude of the modulation. However, singular involvement of emotional factors has been questioned by the findings of a previous study that showed that among emotional arousing stimuli with negative valence, those with pain-related contents are most effective to modulate pain in observers [14]. Additionally, Roy et al. showed that pain expressions are generally rated low on arousal but facilitate pain comparable to studies relying on highly arousing negative pictures [25]. A recent study compared the effect of pain, fear, and joy expressions on heat pain perception and found that only the pain expression produced pain modulation compared with neutral faces [21]. The findings of this study and previous studies suggest that pain-related information, in comparison with emotion-related characteristics, play a more important role in the vicarious modulation of individuals’ responses to pain.
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Aside from the suggestion about the role of emotional factors in the vicarious pain modulation, some studies proposed that a sensorimotor resonance between the communicated pain signal in others (eg, facial expression) and observers’ neural systems may prime responses to pain in observers and might result in increased reactivity to acute pain stimuli. These studies rely on the perceptionaction model, which suggests that, similar to actions, perception of another person’s emotional state occurs through a corresponding activation in the observer’s brain that represents firsthand experience of that emotion [22]. This is supported by studies showing partial overlap between brain activation observed during the perception of pain in others and that associated with the firsthand experience of pain [16,17]. In this context, the observed vicarious facilitation of pain may be explained by the activation of brain areas responsible for the processing of self-pain as the result of resonance with cues signaling pain in others. In addition, previous studies have shown that a higher level of dispositional empathy in the observer is associated with less facilitation of responses to painful stimuli [19,32]. They assumed stronger empathy is associated with attention driven away from experienced pain, which can result in lower pain ratings [20]. However, in our study we failed to replicate those findings, possibly because all participants were instructed to actively attend toward the expressions. 4.2. Neurocognitive modulation of the vicarious facilitation of spinal and supraspinal responses The processing of the movement of a pain expression seems to play an important role in the vicarious modulation of the NFR. It has been shown that viewing dynamic as compared to static expressions results in greater neural activation in the brain of the observer [30]. Consistent with this, the vicarious facilitation of the NFR was previously found in response to passive viewing of dynamic [19] but not static expressions [25,32]. In the present study, the NFR was facilitated by observation of pain expressions with higher levels of pain in the movement rating trials than in the pain rating trials. This implies that stimulus-driven effects induced by dynamic expressions on spinal processes may be inhibited when attention is directed toward higher-order processing of the meaning of the expression. Modulation of corticospinal activity by vicarious pain also has been shown in studies using transcranial magnetic stimulation of the motor cortex. For example, observation of images showing the stimulation of the hand of another person with a needle inhibited the motor evoked potentials by transcranial magnetic stimulation of the observer’s motor cortex for the congruent hand [3] and facilitated the motor evoked potentials for the incongruent hand [4]. The observed inhibition could reflect a reduced sensitivity of the motor cortex involved in a somatotopically specific resonance process, whereas the facilitation at the contralateral hand might be indicative of a generalized vicarious facilitation effect in favor of escape behaviors. Pain expressions do not carry information about spatial properties of the pain of the observed person, so they might produce similar general facilitation of motor defensive responses. A study with the same task used in the current study showed that attention toward dynamic aspects of expressions is associated with a significant increase in blood oxygen level dependent (BOLD) signal in the inferior parietal lobule (IPL) and the premotor areas [7] in comparison with attention toward pain, associated with significantly increased activation in different areas of the brain (eg, medial prefrontal cortex (mPFC)). Modulation of activity in the premotor cortex, which is suggested to be associated with change in corticospinal excitability (eg, inferred from disruption of motor facilitation after action observation) [1,2], may result in diffuse motor priming and increased spinal reflexes via descending facilitation [33]. Aside
from this, several studies have shown that observation of others’ pain is associated with activation in insula, anterior-cingulate cortex, and the supplementary motor area [16,17,28]. These regions may also be involved in moderating the effects of emotion and competing sustained pain on acute self-pain and spinal responses via change in activation of paracentral lobule [21,27] and could have a role in the modulation of the NFR by pain observation. Further investigations are needed to explore how brain regions involved in the perception of pain in others might contribute to vicarious facilitation of spinal nociception and self-pain. 4.3. Differential attention modulation of vicarious pain responses at perceptual and reflexive levels The observed difference between pain ratings (perceptual processing) and the NFR (spinal-nociceptive processing) in attentional effects on vicarious facilitation suggests that separate networks are involved in these 2 modulatory processes. This is in accordance with findings of a number of previous studies clearly showing dissociations between pain-related perceptual and spinal responses [12,26,32]. The multidimensional approach to studying empathy differentiates at least 2 levels in the processing of pain in others [9,11,22]. At the early stage, low-level responses are indicative of involvement of fast and automatic mechanisms subserving alerting and defensive functions. At the later stage, higher-order processing contributes to the self-regulatory mechanisms in the observer in the context of pain communication, which can influence pain perception. The low-level responses can be modulated by descending signals from higher-order structures in the brain. The NFR, as a reflexive low-level response, can be inhibited/facilitated by supraspinal signals (eg, during hypnosis or anticipation of pain) [10,37]. Attention toward the affective dimension of pain in the expression may block the facilitation at the spinal level. One possible mechanism of this modulation is the involvement of prefrontal regions, which have been shown to be activated by attention toward the meaning of dynamic pain expressions [7] and are also involved in the expectation-induced analgesia [36]. Admittedly, this interpretation is speculative and calls for further investigation. 4.4. Limitations and future directions Stimuli included in the current study were only neutral or pain expressions. Inclusion of other types of negative/positive expressions may help to further tease apart nonspecific effects of arousal and valence on spinal nociception [22]. However, 3 studies suggest that these nonspecific emotional dimensions seem insufficient to explain vicarious pain effects [14,23,25]. The present study also did not include a passive observation condition, and we relied on a comparison with our previous studies to interpret the effects of the 2 task conditions. Aside from that, the paradigm did not allow us to assess task demands and their influence on subjects’ responses. It is possible that when observing pain expressions, evaluation of pain intensity is a more natural and automatic task, whereas comparison of movement between different face parts is more attention demanding. However, in this case we would expect to see analgesic effects of distraction (ie, reduced pain responses in the movement task as compared with the pain task) [5,20]. This was, however, not the case here. In addition, perceived social distance could potentially influence responsiveness to emotion in others’ facial expressions [18]; future studies might manipulate (or control) perceived social distance and investigate its influence on vicarious pain responses. Finally, future studies may investigate brain correlates of the attentional modulation of vicarious facilitations and test some of the admittedly speculative hypotheses proposed earlier.
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4.5. Conclusions Communication of pain is influenced by contextual and psychological factors affecting the observers, which may in turn influence their own behavioral, affective, or cognitive reactions to pain [15]. In our study, modulation of observers’ attention toward superficial aspects of pain expressions (movements) or toward the meaning of these expressions resulted in a dissociation between a low-level defensive responses and higher-order processes underlying pain perception. The facilitation of the withdrawal responses seemed to be blocked by the engagement of higher-order processes subserving the extraction of meaning. In line with the perception-action model and previous work showing multiple-level processing of empathic signals, these findings further suggest that vicarious processes rely on at least partly separable networks underlying the cortical processing of pain signals and the descending modulation of pain-related responses. These findings help us to better understand the cognitive mechanisms involved in the communication of pain-related signals. Conflict of interest statement The authors declare no conflict of interest. Acknowledgments
[11] [12]
[13] [14]
[15]
[16] [17]
[18]
[19]
[20] [21] [22] [23]
The authors thank Veronique Taylor for her help during data acquisition. This research was funded by a grant to Pierre Rainville from the National Science Research Council of Canada (NSERC; no. 341472-07/2013). Ali Khatibi was supported by an award from junior mobility program (JuMo) from KU Leuven. Pierre Rainville and Etienne Vachon-Presseau were supported by the Fonds de la recherche Québec–Santé and the Canadian Institutes of Health Research (CIHR), respectively. The contribution of Johan Vlaeyen and Martien Schrooten was supported by the Odysseus Grant ‘‘the Psychology of Pain and Disability Research Program’’ funded by the Research Foundation–Flanders (FWO Vlaanderen, Belgium). Appendix A. Supplementary data
[24]
[25]
[26]
[27] [28]
[29] [30]
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.pain.2014.07.005.
[31]
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