Crossmodal shaping of pain: a multisensory approach to nociception.

Noxious stimuli in our environment are often accompanied by input from other sensory modalities that can affect the processing of these stimuli and the perception of pain. Stimuli from these other modalities may distract us from pain and reduce its perceived strength. Alternatively, they can enhance the saliency of the painful input, leading to an increased pain experience. We discuss factors that influence the crossmodal shaping of pain and highlight the important role of innocuous stimuli in peripersonal space. We propose that frequency-specific modulations in local oscillatory power and in long-range functional connectivity may serve as neural mechanisms underlying the crossmodal shaping of pain. Finally, we provide an outlook on future directions and clinical implications of this promising research field.

Spectral signatures of viewing a needle approaching one's body when anticipating pain.

When viewing the needle of a syringe approaching your skin, anticipation of a painful prick may lead to increased arousal. How this anticipation is reflected in neural oscillatory activity and how it relates to activity within the autonomic nervous system is thus far unknown. Recently, we found that viewing needle pricks compared with Q-tip touches increases the pupil dilation response (PDR) and perceived unpleasantness of electrical stimuli. Here, we used high-density electroencephalography to investigate whether anticipatory oscillatory activity predicts the unpleasantness of electrical stimuli and PDR while viewing a needle approaching a hand that is perceived as one's own. We presented video clips of needle pricks and Q-tip touches, and delivered spatiotemporally aligned painful and nonpainful intracutaneous electrical stimuli. The perceived unpleasantness of electrical stimuli and the PDR were enhanced when participants viewed needle pricks compared with Q-tip touches. Source reconstruction using linear beamforming revealed reduced alpha-band activity in the posterior cingulate cortex (PCC) and fusiform gyrus before the onset of electrical stimuli when participants viewed needle pricks compared with Q-tip touches. Moreover, alpha-band activity in the PCC predicted PDR on a single trial level. The anticipatory reduction of alpha-band activity in the PCC may reflect a neural mechanism that serves to protect the body from forthcoming harm by facilitating the preparation of adequate defense responses.

Crossmodal bias of visual input on pain perception and pain-induced beta activity.

In our environment, acute pain is often accompanied by input from other sensory modalities, like visual stimuli, which can facilitate pain processing. To date, it is not well understood how these inputs influence the perception and processing of pain. Previous studies on integrative processing between sensory modalities other than pain have shown that multisensory response gains are strongest when the constituent unimodal stimuli are minimally effective in evoking responses. This finding has been termed the principle of inverse effectiveness (IE). In this high-density electroencephalography study, we investigated the influence of Gabor patches of low and high contrast levels on the perception and processing of spatially and temporally aligned painful electrical stimuli of low and high intensities. Subjective pain ratings, event-related potentials (ERPs) and oscillatory responses served as dependent measures. In line with the principle of IE, stronger crossmodal biasing effects of visual input on subjective pain ratings were found for low compared to high intensity painful stimuli. This effect was paralleled by stronger bimodal interactions in right-central ERPs (150-200ms) for low compared to high intensity pain stimuli. Moreover, an enhanced suppression of medio-central beta-band activity (12-24Hz, 200-400ms) was found for low compared to high intensity pain stimuli. Our findings possibly reflect a facilitation of stimulus processing that serves to enhance response readiness of the sensorimotor system following painful stimulation. Taken together, our study demonstrates that multisensory processing between visual and painful stimuli follows the principle of IE and suggests a role for beta-band oscillations in the crossmodal modulation of pain.

Viewing a needle pricking a hand that you perceive as yours enhances unpleasantness of pain.

"Don't look and it won't hurt" is commonly heard advice when receiving an injection, which implies that observing needle pricks enhances pain perception. Throughout our lives, we repeatedly learn that sharp objects cause pain when penetrating our skin, but situational expectations, like information given by the clinician prior to an injection, may also influence how viewing needle pricks affects forthcoming pain. How both previous experiences and acute situational expectations related to viewing needle pricks modulate pain perception is unknown. We presented participants with video clips of a hand perceived as their own being either pricked by a needle or touched by a Q-tip, while concurrently applying painful or nonpainful electrical stimuli. Intensity and unpleasantness ratings, as well as pupil dilation responses, were monitored. Effects of situational expectations about the strength of electrical stimuli were investigated by manipulating the contingency between clips and electrical stimuli across experimental blocks. Participants were explicitly informed about the contingency. Intensity ratings of electrical stimuli were higher when a clip was associated with expectation of painful compared to nonpainful stimuli, suggesting that situational expectations about forthcoming pain bias perceived intensity. Unpleasantness ratings and pupil dilation responses were higher when participants viewed a needle prick, compared to when they viewed a Q-tip touch, suggesting that previous experiences with viewing needle pricks primarily act upon perceived unpleasantness. Thus, remote painful experiences with viewing needle pricks, together with information given prior to an injection, differentially shape the impact of viewing a needle prick on pain perception.

Multisensory interactions in early evoked brain activity follow the principle of inverse effectiveness.

A major determinant of multisensory integration, derived from single-neuron studies in animals, is the principle of inverse effectiveness (IE), which describes the phenomenon whereby maximal multisensory response enhancements occur when the constituent unisensory stimuli are minimally effective in evoking responses. Human behavioral studies, which have shown that multisensory interactions are strongest when stimuli are low in intensity are in agreement with the IE principle, but the neurophysiologic basis for this finding is unknown. In this high-density electroencephalography (EEG) study, we examined effects of stimulus intensity on multisensory audiovisual processing in event-related potentials (ERPs) and response time (RT) facilitation in the bisensory redundant target effect (RTE). The RTE describes that RTs are faster for bisensory redundant targets than for the respective unisensory targets. Participants were presented with semantically meaningless unisensory auditory, unisensory visual and bisensory audiovisual stimuli of low, middle and high intensity, while they were instructed to make a speeded button response when a stimulus in either modality was presented. Behavioral data showed that the RTE exceeded predictions on the basis of probability summations of unisensory RTs, indicative of integrative multisensory processing, but only for low intensity stimuli. Paralleling this finding, multisensory interactions in short latency (40-60ms) ERPs with a left posterior and right anterior topography were found particularly for stimuli with low intensity. Our findings demonstrate that the IE principle is applicable to early multisensory processing in humans.

You can see pain in the eye: pupillometry as an index of pain intensity under different luminance conditions.

Pupil dilation is regulated autonomically and it may be a valid measure of pain, but pupillometry for pain intensity recordings has not been evaluated under different luminance conditions. We hypothesized that the pupil response may serve as an objective indicator of pain intensity even if luminance conditions differ which is often the case in experiments with pictures. In 20 healthy females we applied a tonic pressure pain to the fingers (20 s). During pain induction, participants looked at pictures of three different levels of luminance. Pupil dilation was recorded continuously. Immediately after pain onset, there was a significant pupil dilation which reached its maximum about 2 s after pain onset. While this maximum pupil dilation did not differ with pressure intensity, the pupil dilation was larger for the higher pressure intensity in the period from 10 s after pressure onset to pressure offset. Even under different luminance conditions, pupillometry can serve as an objective indicator of pressure pain intensity. Thus, it seems promising to use pupillometry with complex experimental designs combining pain and pictorial stimuli.