The visual size of one׳s own hand modulates pain anticipation and perception

Neuropsychologia 57 (2014) 93–100

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Neuropsychologia journal homepage: www.elsevier.com/locate/neuropsychologia

The visual size of one's own hand modulates pain anticipation and perception Daniele Romano, Angelo Maravita n Psychology Department, Università degli studi di Milano-Bicocca, Piazza dell’Ateneo Nuovo, 1, 20126 Milan, Italy

art ic l e i nf o

a b s t r a c t

Article history: Received 18 September 2013 Received in revised form 4 March 2014 Accepted 10 March 2014 Available online 18 March 2014

How to reduce pain is a fundamental clinical and experimental question. Acute pain is a complex experience which seems to emerge from the co-activation of two main processes, namely the nociceptive/discriminative analysis and the affective/cognitive evaluation of the painful stimulus. Recently it has been found that pain threshold increases following the visual magnification of the body part targeted by the painful stimulation. This finding is compatible with the well-known notion that body representation and perceptual experience relay on complex, multisensory factors. However, the level of cognitive processing and the physiological mechanisms underlying this analgesic effect are still to be investigated. In the present work we found that following the visual magnification of a body part, the Skin Conductance Responses (SCR), to an approaching painful stimulus increases before contact and decreases following the real stimulation, compared to the non-distorted view of the hand. By contrast, an unspecific SCR increase is found when the hand is visually shrunk. Moreover a reduction of subjective pain experience was found specifically for the magnified hand in explicit pain ratings. These findings suggest that the visual increase of body size enhances the cognitive, anticipatory component of pain processing; such an anticipatory reaction reduces the response to the following contact with the noxious stimulus. The present results support the idea that cognitive aspects of pain experience relay on the multisensory representation of the body, and that could be usefully exploited for inducing a significant reduction of subjective pain experience. & 2014 Elsevier Ltd. All rights reserved.

Keywords: Analgesia Skin Conductance Response Body representation Vision Pain anticipation Multisensory

1. Introduction Pain is an extremely common daily-life sensory experience. Acute pain is a complex sensation usually generated by nociceptive input (Treede, 2006) even if it is possible to feel pain in the absence of nociception (Craig, Reiman, Evans, & Bushnell, 1996; Craig, 2002; Ehrsson, Wiech, Weiskopf, Dolan, & Passingham, 2007; Lloyd, Morrison, & Roberts, 2006). As a complex sensation, pain experience seems to emerge from the co-activation of a distributed brain network, originally called neuromatrix (Melzack, 1989) and currently referred to as pain matrix (Ploghaus, 1999), which comprises brain areas related to primary discriminativesomatosensory analysis, namely S1 and S2, as well as associative multimodal areas including the posterior parietal cortex, anterior insula and anterior cingulate cortex (ACC) (Iannetti & Mouraux, 2010; Price, 2000).

n

Corresponding author. Tel.: þ 39 02 64483768; fax: þ 39 02 64483788. E-mail addresses: [email protected] (D. Romano), [email protected] (A. Maravita). http://dx.doi.org/10.1016/j.neuropsychologia.2014.03.002 0028-3932/& 2014 Elsevier Ltd. All rights reserved.

Such a complex brain substrate is justified by the multicomponential nature of pain experience that includes both cognitive and sensory aspects. This is nicely shown by the experimental modulation of pain experience through a large range of experimental manipulations including crossmodal signals (Gallace, Torta, Moseley, & Iannetti, 2011; Longo, Betti, Aglioti, & Haggard, 2009; Romano, Pfeiffer, Maravita, & Blanke, 2014), emotions or meditation-induced states (Brown & Jones, 2010; Rhudy, Bartley, & Williams, 2010; Rhudy, Williams, McCabe, Russell, & Maynard, 2008; Williams & Rhudy, 2009; Zeidan et al., 2011), attention and expectations (Babiloni et al., 2008; Brown & Jones, 2008; Brown, Seymour, Boyle, El-Deredy, & Jones, 2008; Clark, Brown, Jones, & El-Deredy, 2008; Porro et al., 2002) and social factors (Avenanti, Sirigu, & Aglioti, 2010; Forgiarini, Gallucci, & Maravita, 2011). Notably to our purpose, although nociceptive stimuli are processed through specific sensory pathways (Haggard, Iannetti, & Longo, 2013; Lenz, Casey, Jones, & Willis, 2010), pain experience has been successfully modulated through vision (Longo, Iannetti, Mancini, Driver, & Haggard, 2012; Longo et al., 2009). In particular, the distortion of the visual feedback relative to the body part affected by pain can strongly modulate painful sensations and has

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been proposed as a candidate for the reduction of pain in clinical conditions (Moseley, Parsons, & Spence, 2008; Ramachandran, Brang, & McGeoch, 2009). However the results of such a sensory distortion are not univocal. While in some reports the level of perceived pain has been increased by the magnification of the visual size of a hand targeted by the painful stimulus (Moseley et al., 2008) in other cases the same visual distortion has led to pain reduction (Mancini, Longo, Kammers, & Haggard, 2011). Furthermore, the neurophysiological underpinnings of this kind of modulation are still to be clarified. In the current study we sought for further evidence about the effect of visual body distortion on subjective pain experience as well as its physiological correlates. The working hypothesis is that the vision of an enlarged body part may increase the preparation of the sensory system to the consequence of the incoming noxious stimulus, leading to subsequent decrease in response, once the stimulus contacts the skin. To this aim we designed an experimental paradigm where we measured the anticipatory physiological response of participants exposed to an incoming harmful stimulus, as well as the somatosensory response when the stimulus eventually touches the skin. Therefore, Skin Conductance Response (SCR) was recorded following the application of painful or harmless stimuli (Cheng et al., 2007; Romano, Gandola, Bottini, & Maravita, 2014) that touched the hand or simply approached the skin without eventually contacting it. In the former situation we expected, at baseline, a response due to the sensory processing of the nociceptive stimulation, while in the latter we expected a smaller, but still measurable response, due to the affective/cognitive anticipatory response to pain (Clark et al., 2008; Romano, Gandola, Bottini, & Maravita, 2014). Critically these measures were also taken both under real-size, or distorted vision of the participant's hand, in order to measure the effect of visual distortion on the anticipatory and sensory aspects of pain processing. Moreover, in separate experiments, we assessed the explicit experience of pain intensity and unpleasantness under the same circumstances of visual distortion.

2. Experiment 1 (pain anticipation) 2.1. Materials and methods 2.1.1. Subjects 12 right handed, healthy participants (6 females, mean age ¼24.32, s.d. ¼ 2.1), recruited among the students attending the Università degli Studi di MilanoBicocca took part in Experiment 1 after giving their informed consent and received course credits for their participation. The experimental protocol was explained in detail, but the participants were blind to the purpose of the experiment. The experiment was conducted according to the principles of the Declaration of Helsinki (World Medical Organization, 1996). 2.1.2. Somatosensory stimuli Two different kinds of stimuli were delivered: noxious (non-invasive needle with a blunt end) and neutral (cotton swab) (Cheng et al., 2007; Höfle, Hauck, Engel, & Senkowski, 2012; Romano, Gandola, Bottini, & Maravita, 2014). The stimuli could be delivered in two contact conditions: real or simulated (Factor: Contact). In the real contact condition the needle and the cotton swab were applied to the pad of the middle finger for about .5 s. In the simulated contact condition the stimuli approached the same area, but stopped at around half centimeter above the fingertip, where they were kept for about .5 s and then retracted. Non-painful tactile stimuli were delivered in order to compute the anticipatory response to pain and to reduce SCR adaptation that typically follows repetitive stimulation (Levinson & Edelberg, 1985). Stimuli were either applied to the right or the left hand, according to eight different experimental conditions: Painful Real Right, Painful Real Left, Painful Simulated Right, Painful Simulated Left, Neutral Real Right, Neutral Real Left, Neutral Simulated Right, Neutral Simulated Left. 2.1.3. SCR hardware and software SCR was collected through a SC-2701 biosignal amplifier (Bioderm, UFI, Morro Bay, California) connected to a dedicated PC through a serial port. The gain

parameter was set at 10 mmho/V; the signal was sampled at 10 Hz. The signal was recorded by means of two silver electrodes (1081 FG Skin Conductance Electrode) placed on the first phalanx of the index and ring fingers of the right hand for half of the participants and on the left for the other half. A saline conductive paste was applied to the electrodes in order to improve signal-to-noise ratio. Data were digitalized at 12-bit resolution using the SC-2701 dedicated software. 2.1.4. Experimental procedure Participants sat comfortably at a table with the experimenter sitting in front of them. They were asked to put both hands, palm up on the table. Each trial started with participants gazing at the fixation point drawn at the center of a 40-cm high vertical opaque board, placed at 50 cm distance in front of them. On each trial, a trained experimenter delivered one of two somatosensory stimuli (Factor: Stimulus) to one of the two hands (Factor: Hand), by approaching it with a smooth, continuous movement eventually contacting the hand or not (Factor: Contact). The experimenter, (an undergraduate student attending at the University of MilanoBicocca), who was running the experiment as part of her internship, was trained to deliver the stimulation as constant as possible and was blind to the specific purpose of the experiment. Neutral or painful stimuli emerged from behind the opaque board unpredictably and in random sequence, while participants were requested to gaze at them along their entire trajectory. A total of 64 tactile and noxious stimuli were delivered to each participant in a single session, while the Skin Conductance Response (SCR) was recorded continuously. The 64 stimuli were divided into 8 independent blocks of 8 stimuli each (1 per condition) and were delivered in random order within each block. A pause was introduced after 4 blocks, or at the end of any block when needed. The entire session lasted around 30 min. 2.1.5. Data pre-processing The SCR peak-to-base measure (Breimhorst et al., 2011; Lykken & Venables, 1971; Rhudy et al., 2010) was computed for each trial as the difference between the maximum value detected in a 6-s post-stimulus time window and the baseline calculated as the average value of a 300-ms pre-stimulus time window (Romano, Gandola, Bottini, & Maravita, 2014). Manual markers identifying each stimulus type were added to the SCR trace through the computer keyboard at the moment when the stimulus emerged from behind the opaque shield. 2.1.6. Data analysis Data were analyzed with STATISTICA 6.0 (StatSoft, Italy, http://www.statsoft.it), and GnPower 3.1 (http://www.psycho.uni-duesseldorf.de/abteilungen/aap/gpo wer3/). A General Linear Model was used on SCR data, factoring: Stimulus (painful/ neutral), Contact (real/simulated) and Hand (left/right), as within subject factors. This resulted in a 2  2  2 repeated-measure ANOVA design. Significant level was set at o.05, Fisher post-hoc tests were used when appropriate.

2.2. Results The ANOVA showed a main effect of Stimulus (F1,11 ¼14.426, po.01; η2 ¼ .567, power¼.932; painful¼.17 (average) μS (microSiemens)7.04 (St. err.), neutral¼.02 μS7.02) and a main effect of Contact (F1,11 ¼ 15.411, po.01; η2 ¼.584, power¼.946; real¼.12 mS7 .03, simulated¼.07 mS7.03); moreover the interaction between Stimulus and Contact was significant (F1,11 ¼8.61, pr.01; η2 ¼.439, power¼.97; painful real¼.22 mS7.06, painful simulated¼.12 mS7 .04, neutral real¼ .02 mS7.01, neutral simulated¼.02 mS7.02). The main effect Hand (F1,11 ¼.116, p¼.74; η2 ¼ .010, power¼.061) and the other interactions were not significant. Post-hoc comparisons showed that painful real stimulations induced stronger SCR than all other conditions (all p o.01), but also that painful simulated stimuli induced larger SCR than neutral stimuli (all p o.01); finally neutral real and neutral simulated stimuli yielded a small, comparable SCR (p ¼.93) (Fig. 1). This pattern of results confirms that our experimental noxious stimuli evoked an anticipatory response when they approached the skin, and a subsequent somatosensory response on skin contact. Overall, the response produced by the neutral stimuli was negligible and unable to differentiate the anticipatory from the somatosensory component; for this reason neutral stimuli were not considered in the analysis of the following experiments.

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Fig. 1. Pain anticipation protocol results. The mean value for the real contact stimulations (light gray) and the simulated contact stimulations (dark gray). Thin bars indicate standard error, asterisks show significant differences, n.s. indicates non-significant differences.

3. Experiment 2 (magnified-hand manipulation) 3.1. Materials and methods 3.1.1. Subjects 38 new healthy, naïve participants, recruited among the students of the Università degli Studi di Milano-Bicocca took part in Experiment 2: 18 (14 females, mean age¼24.09, s.d. ¼2.25) in Experiment 2a; 20 in Experiment 2b (14 females, mean age¼ 23.85, s.d.¼ 1.84). Participants gave their informed consent and received course credits for participation. The experiment was conducted according to the principles of the Declaration of Helsinki (World Medical Organization, 1996).

3.1.2. Experiment 2a (big Hand – SCR) 3.1.2.1. Stimuli and procedure. The experimental stimuli were the same used in Experiment 1. In addition, participants looked at one of their hands, through a lens with a magnification factor of 2  , and at the other hand through a neutral lens. With this arrangement one hand (the left in half participants, the right in the other half) appeared visually magnified, while the other was perceived at normal size. Furthermore, the fingertips of both hands were shielded from view by a small opaque screen, so that the stimuli remained visible for their whole trajectory, except for the last 3 cm. With this arrangement, the final contact between the hand and the stimulus was invisible, in order to avoid any visual distortion of the stimulus size, when it passed below the magnifying lens (see Fig. 2 for a schematic view of the setup). The experimenter was a new trained student, attending the University of Milano-Bicocca, and blind to the specific purpose of the experiment.

3.1.2.2. Data analysis. Data were analyzed with STATISTICA 6.0 (StatSoft, Italy, htt p://www.statsoft.it). A 2  2 repeated-measure ANOVA was conducted, after checking for normality of data distribution, on the SCR to painful stimuli with the factors: Stimulus contact (real/simulated) and Hand (big/normal), in order to assess the effect of visual distortion on the anticipatory and nociceptive components of pain processing. Significance level was set at p o .05, Fisher's LSD post-hoc test was used to explore significant interaction.

3.1.3. Experiment 2b (big hand – pain ratings) The experimental procedure was the same of Experiment 2a, except for the following differences. First, explicit pain ratings were collected (see below) instead of SCR. Second, since in this case we were interested in explicit pain ratings, only the 32 real contact stimulations (and not the simulated ones) were delivered, following the same procedure of Experiment 2a.

3.1.3.1. Pain ratings. We investigated the subjective experience of pain by asking participants to rate both the intensity and unpleasantness of each stimulus, soon after it was delivered. Participants answered to each question through a Visual Analogue Scale (VAS) ranging from 0 to 100 mm where 0 indicated not unpleasant

Fig. 2. Setting Exp 2a and Exp 2b. Schematic vision of the experimental setting: both hands were visible, but one could be perceived through a magnifying lens, thus it was perceived as visually enlarged. The tips of the fingers were not visible in order to prevent the magnification of the stimuli that eventually touched the hands. at all/minimum intensity, and 100 corresponded to the worst unpleasantness/strongest intensity imaginable (Longo et al., 2009).

3.1.3.2. Data analysis. Data from each question underwent an intra-subject standardization by means of an ipsatization procedure, in order to neutralize the effect of response set (Broughton & Wasel, 1990; Cattell, 1944). Specifically, each rating was subtracted by the mean overall ratings of the subject to both questions and in all conditions, and then divided by the standard deviation of subject's ratings to all questions and conditions. Ipsatization transformed questionnaire ratings in Z-scores with a normal distribution, allowing a proper use of parametric tests (Broughton & Wasel, 1990; Cattell, 1944). A repeated-measure ANOVA was conducted on ipsatized values of painful stimuli resulting in a 2  2 within-subject design factoring Scale (intensity/unpleasantness) and Hand (big/normal). Significance level was set at po.05, as in Experiment 2a and Fisher LSD test was used for post-hoc comparisons.

3.2. Results 3.2.1. Exp 2a Skin Conductance Response The ANOVA revealed significant differences for the main factor Stimulus contact (F1,17 ¼32.368, po.001, η2 ¼.656, power4.999) with a larger response for real (.71 mS7.1) than for simulated (.48 mS7.08) painful stimuli, while the main factor Hand was not statistically significant (F1,17 ¼ .288, p¼.598, η2 ¼.017, power¼.08). Furthermore, and critical to our aim, there was a significant Contact  Hand interaction (F1,17 ¼ 11.911, pr.01, η2 ¼.412, power¼.999) (Fig. 3a). Post-hoc tests revealed that the real contact stimulation had a smaller SCR in the visually distorted hand (p ¼.009, Big ¼ .66 mS7.1, Normal ¼.76 mS7 .1). By contrast, an opposite trend was observed for the simulated contact conditions (p¼ .066, Big¼ .52 mS7.09, Normal¼.45 mS 7.08). In summary, the vision of a visually magnified hand induced an initially stronger anticipatory response, followed by a reduced response on stimulus contact, as compared to the non-distorted hand (Fig. 3c illustrates the SCR of a representative participant). 3.2.2. Exp 2b VAS questionnaire The ANOVA on pain ratings did not show any significant main effect (Scale: F1,19 ¼ 2.899, p¼.105,η2 ¼ .133, power¼.367; hand: F1,19 ¼ 1.741, p¼.203, η2 ¼ .084, power¼.241), while the Hand  Scale interaction was significant (F1,19 ¼4.279, pr.05, η2 ¼.185, power¼.842).

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scale-normal size¼ .0267.07, intensity scale-big size¼.0797.07, intensity scale-normal size¼ .1077.08), suggesting that our participants referred a less unpleasant experience following the stimulation of the magnified hand, while reporting similar pain intensity for both hands (Fig. 3b).

4. Experiment 3 (shrunken-hand manipulation) 4.1. Materials and methods 4.1.1. Subjects 38 new healthy naïve participants took part in this experiment: 18 (12 females, mean age¼23.77, s.d.¼ 3.77) in Experiment 3a and 20 in Experiment 3b (16 females, mean age¼ 25.05, s.d. ¼5.93). Participants were all students at the Università degli Studi di Milano-Bicocca, gave their informed consent and received course credits for their participation. The experiment was conducted according to the principles of the Declaration of Helsinki (World Medical Organization, 1996). 4.1.2. Experiment 3a (small Hand – SCR) The experimental procedure, data processing and analysis were the same as Experiment 2a except for the type of visual distortion introduced. Here the visual feedback from one hand was systematically minified (instead of magnified) with a χ2 factor. In order to achieve the desired visual distortion, a wooden structure was crafted (Fig. 4), which held a binocular comprising a reverse telescope (Moseley et al., 2008) on one side, and a neutral lens on the other. As in Experiment 2a, the arrangement allowed the participant to see both hands through the ocular, one minified and one at normal size, with the exception of the fingertips that were not visible. Either the left or right hand was visually distorted, following a counterbalanced order among participants. 4.1.3. Experiment 3b (small Hand – pain ratings) The experimental procedure, data processing and analysis were the same as in experiment 2b except for the type of visual distortion, now consisting in a minified view of one hand.

4.2. Results 4.2.1. Exp 3a Skin Conductance Response In the ANOVA, a significant difference was found for the main factor Stimulus contact (F1,17 ¼16.381, p o.001, η2 ¼.491, power¼.968) with the real contact stimulus inducing a larger response (.70 mS7.1) than the simulated pinprick (.58 mS7 .1). The main factor Hand was also significant (F1,17 ¼ 4.708, p ¼.044, η2 ¼.217, power¼ .534) with the small hand eliciting an overall increased SCR (.67 mS7.1), than the normal size hand (.62 mS7 .1). Differently from Experiment 2a, and crucially, the interaction between the two factors was not significant (F1,17 ¼1.085, p¼ .312, η2 ¼ .060, power ¼.276) (Fig. 5a). In summary, a general

Fig. 3. Experiment 2-Big Hand experiments results. The mean value for the big hand (light gray) and the normal-size hand (dark gray). Thin bars indicate standard error, asterisks show significant differences, the circle indicates a nearly significant difference. (a) Experiment 2a: SCR to painful stimuli; (b) Experiment 2b: ipsatized ratings for painful stimuli; (c) SCR response of a representative participant of the Experiment 2a.

Post-hoc tests showed that the unpleasantness scale rating for the big hand stimulation (z-score7Standard Error¼  .2127.12) was significantly lower than the other three ratings (all po.01; unpleasantness

Fig. 4. Setting Exp 3. The wooden structure specifically designed for the visual shrinking of the hand. One ocular (left one in figure) provided a minified vision of the hand, while the other was neutral.

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4.2.2. Exp 3b VAS questionnaire The ANOVA showed a main effect of the Scale factor (F1,19 ¼6.69, p r.01, η2 ¼ .259, power¼ .657; intensity¼ .117 7.04, unpleasantness ¼ .117 7.09); the other main factor Hand (F1,19 ¼.49, p ¼.492, η2 ¼ .026, power¼ .103) and the Hand  Scale interaction (F1,19 ¼2.332, p ¼.143, η2 ¼.111, power ¼.56) were not significant (Fig. 5b).

5. Discussion

Fig. 5. Experiment 3-Small Hand experiments results. The mean value for the small hand (light gray) and the normal-size hand (dark gray). Thin bars indicate standard error, asterisks show significant differences. (a) Experiment 3a: SCR to painful stimuli; (b) Experiment 3b: ipsatized ratings for the painful stimuli; (c) SCR response of a representative participant of the Experiment 3a.

increase of response to the minified hand was found, without any difference between simulated and real contact stimuli (see Fig. 5c for the SCR of a representative participant).

In the present study we investigated how pain processing can be modulated by the ongoing visual distortion of one's own hand targeted by a harmful stimulus. First we aimed at investigating whether noxious stimuli induced stronger Skin Conductance Responses than neutral stimuli. Moreover we sought for dissociating the cognitive and the sensory-nociceptive component of pain experience. We found that painful stimuli induced stronger autonomic responses than neutrals and, critically, that painful stimuli in the simulated contact condition induced stronger SCR than simulated and real contact neutral stimuli. Moreover, as expected, the strongest SCR was recorded when the noxious stimulus actually touched the hand, as a consequence of the additional contribution of nociception to the cognitive aspects of pain (i.e., response to simulated contact). Interestingly, the level of response of both hands was similar in the absence of visual distortions. These results attests for the suitability of the present novel paradigm for the assessment of the anticipatory and the somatosensory components of pain processing independently. In particular, the anticipatory response is considered as an index of the affective/cognitive component of pain experience (Clark et al., 2008; Colloca, Benedetti, & Pollo, 2006; Ploghaus, 1999; Watson et al., 2009). By contrast, in Experiment 1 we did not observe different SCR in real and simulated contact for neutral stimuli, suggesting that changes in the processing of tactile non-painful stimuli, likely to elicit very little arousal responses, cannot be reliably detected using our SCR paradigm. However, our crucial interest was the modulation of pain processing following the visual distortion of one's own hand. While many previous studies investigated the response to noxious stimuli only by means of explicit pain ratings (Brown et al., 2008; Longo et al., 2009; Moseley et al., 2008; Ramachandran et al., 2009) or subjective pain threshold (Hänsel, Lenggenhager, von Känel, Curatolo, & Blanke, 2011; Mancini et al., 2011), here we wished to assess the physiological markers of the processing of incoming noxious events. Furthermore, as in previous studies, we also assessed the explicit report of pain intensity and unpleasantness, i.e., the sensory-discriminative and affective components of pain experience (Rainville, Carrier, Hofbauer, Bushnell, & Duncan, 1999). Physiological and explicit aspect of pain processing were assessed through a between-subject design, that represents a drawback of the current study, limiting the possibility to directly correlate physiological measures and explicit ratings. However, this approach was preferred to the collection of either trial-by-trial explicit ratings, which could have influenced the concurrent SCR signal, or the overall rating at the end of each block, susceptible of post-perceptual memory confounds (Jensen, Mardekian, Lakshminarayanan, & Boye, 2008; Redelmeier & Kahneman, 1996). The present experimental paradigm led us to differentiate the cognitive/affective from the somatosensory responses to noxious stimuli, in order to cast light on the physiological underpinnings of the effect of visual body distortion on different levels of pain processing. Specifically, in Experiment 2a we found a reduced SCR for the real contact stimulation delivered on the visually magnified hand. Such a reduced physiological response suggests that the visual

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magnification of the body can reduce the sensory response to a noxious stimulus, in line with recent findings by Mancini et al. (2011), who showed that the increased visual size of one's own hand can lead to increased pain threshold. However, our results go beyond previous findings by showing that the reduced SCR to real contact noxious stimuli in the condition of visual magnification is associated with increased anticipatory SCR when noxious stimuli simply approach the skin without touching it. We hypothesized that looking at a visually increased body part might increase the sensory analysis of the visual scene at different stages. It is known that the processing of non-painful tactile stimuli is modulated by the vision of one's own hand: Haggard and coworkers described the Visual Enhancement of touch, consisting of increased tactile discrimination to the vision of a visually magnified area of the skin. The hypothesis advanced to explain this finding is a fast redefinition of cortical maps driven by crossmodal effects of vision on tactile receptive fields (Kennett, Taylor-Clarke, & Haggard, 2001). Furthermore, Pavani and Zampini (2007), by means of the rubber hand illusion paradigm (Botvinick & Cohen, 1998), showed that the visual size of the hand modulates the feeling of ownership felt toward it. One may also speculate that the vision of an enlarged body part may affect the attentional processing of the incoming noxious stimulus; along this line, Babiloni et al. (2004) have found that pain anticipation is strongly related to top-down attentional enhancement of primary somatosensory cortex activity in the somatotopic region waiting for the stimulus, accompanied by decreased activity in the surrounding regions. Such anticipatory arousal response to the approaching painful stimulus could then be followed by decreased sensory activation when the noxious stimulus eventually contacts the body. Different mechanisms, at present still speculative, could be responsible for this effect: on one hand, the anticipatory response may induce the activation of endogenous descending analgesic neural pathways (Fields, Basbaum, & Heinricher, 2006), involving subcortical reticular structures that target the dorsal horns of the spinal cord gray matter, reducing afferent noxious signals. This interpretation could be logically related to the principle of diffuse noxious inhibitory control, whereby a noxious stimulus decreases the response (or increases the threshold) to a following painful stimulus, as assessed through experimental paradigms in animals (LeBars, Dickenson and Besson, 1979a, 1979b) and humans (see for review: Pud, Granovsky, & Yarnitsky, 2009). On the other hand, the expectation of the incoming painful stimulus may induce a pre-activation of early somatosensory regions with a subsequent decreased response once noxious signals reach the cortex (Porro et al., 2002). Finally, a better preliminary visual analysis in the anticipatory phase may increase the expectancy relative to the forthcoming sensory experience of pain, but then decrease the general saliency, and thus sensory response, of the subsequent painful stimulation (Iannetti & Mouraux, 2010; Legrain, Iannetti, Plaghki, & Mouraux, 2011). In this view, Brown et al., 2008 showed that greater certainty about incoming pain modulates the expectancy about pain perception, possibly through a reduced recruitment of attentional resources to the ascending nociceptive input. Whatever the mechanism, it is noteworthy that a different pattern of SCR was found in Experiment 3a, where a minified vision of the hand was provided: here we found a general increase of SCR for both real and simulated contact. The pattern of results of Experiment 3a excludes that the reduced response to real contact stimuli, observed for the enlarged hand, was due to a generic effect of the visual distortion. Indeed, while both visual distortions produced an increased anticipatory response, real contact stimuli induced reduced SCR with the magnified hand but increase SCR with the minified hand.

The increased general SCR following visual reduction of hand size is likely to be due to a general feeling of uneasiness or nonfamiliarity induced by the vision of one's own body parts at a reduced size (e.g., see discussion in Moseley et al., 2008).1 In line with these results, Mancini et al. (2011) found different effects between visual enlargement and reduction of the stimulated hand in a pain threshold paradigm. Here, although we found a different pattern of results between the two visual distortions, we failed to observe a reversal of SCR comparable to the reversal of pain threshold of Mancini et al. (2011). In this respect, it is interesting to note that, in previous work, it has been typically found that the vision of a shrunken body part is less likely to induce perceptual illusions (de Vignemont, Ehrsson, & Haggard, 2005; Pavani & Zampini, 2007) as well as kinematic effects in visuo-motor tasks (Bernardi et al., 2013; Marino, Stucchi, Nava, Haggard, & Maravita, 2010). Overall, the brain might be less prone to use the visual information coming from the minified hand in order to adequately anticipate the incoming experience of pain. Noteworthy, besides the specific reduction of SCR to painful stimuli following the visual magnification of the hand, the pain ratings showed that the visual magnification of the hand selectively reduced the unpleasantness of the nociceptive stimulation and not its perceived intensity, suggesting that the analgesic effect is more related to the affective/cognitive component of pain than to its strict sensory analysis. It is worth noting that, in future studies, the assessment of pain ratings in a paradigm not comprising a visual distortion of one hand, would be advisable to obtain a safer baseline (see footnote 1), also considering the high intersubject variability of the present sample. Furthermore, in a future study, the use of more standardized noxious stimuli, would help to reduce intersubject variability and give cleaner results. Although our results with visual increase of body size are in line with recent experimental findings (Mancini et al., 2011), they are in sharp contrast with previous outcomes showing analgesic effects induced by an opposite visual distortion of the body size (i.e., a reduction). In one patient with chronic phantom limb pain (Ramachandran et al., 2009) were able to modulate the painful sensation by providing a distorted visual feedback through a Mirror Box apparatus (Ramachandran, Rogers-Ramachandran, & Cobb, 1995; Ramachandran & Rogers-Ramachandran, 1996). With this technique, the intact hand is reflected on a parasagittal mirror, thus providing an image compatible with that of the missing limb. Critically, painful sensations from the phantom limb were reduced to a higher degree following visual reduction than visual magnification of the reflected image of the hand. In another study Moseley et al. (2008) found that a visual magnification of the hand produced an increased pain and swelling sensation in patients with chronic pain. The differences, between our study and those by Moseley et al. (2008) and Ramachandran et al. (2009), might be explained in terms of experimental populations and protocols proposed, which comprised healthy participants, receiving acute painful stimulations in our study and patients affected by chronic pain in the above cited works. Different neural mechanisms are likely to underpin chronic and acute pain (Moseley, Sim, Henry, & Souvlis, 2005); moreover chronic pain induces long lasting modification of the body representation (Moseley et al., 2005; Moseley, 2005) that could, per se, change the patterns of response induced by distorted visual feedback from the body.

1 In this respect, one could hypothesize a possible transfer of the visual distortion to the non-distorted hand. However, although this mechanism could have masked any difference between simulated and real contact conditions with the minified hand, it would not explain the positive result in the big-hand condition.

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In conclusion, we suggest that the vision of an enlarged hand would favor the monitoring of incoming somatosensory experience, including pain, as shown by the higher preparatory autonomic response to approaching harmful stimuli. Such a greater anticipation would result in a less pronounced response once the harmful stimulus actually touches the skin. By contrast, if the body part is visually reduced, only a general increase of arousal is observed, following the stimulation. The present novel findings contribute to uncover the physiological and behavioral effects of multisensory body representation for pain processing and suggest that the manipulation of the former could be strategically used to modulate the latter in clinical populations.

Acknowledgments Authors have not conflict of interest for any aspect of the work. This work was supported by a grant from the University of MilanoBicocca (FAR) to AM. We would like to thank Annalisa Benetello for her help in revising the manuscript.

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