The influence of movement upon sensory systems is typically adaptive. Wurtz [3] proposed that saccades inhibit the visual system to avoid the perception of blur during movement. Others have suggested that sound-making movements may suppress the auditory system to prevent damage and maintain auditory sensitivity [6] . Both touch and itch inhibit the somatosensory cortex, preventing redundant information from ascending to the brain [12] . Similarly, self-generated movement may depress pain perception by blocking ascending nociceptive signals, which could suppress pain in situations where the organism needs to engage in fight-or-flight responses to survive.

Our data support past studies that demonstrated movement-induced suppression of various sensory input, including visual, auditory and somatosensory. For example, saccades reduced the brightness of sight [22] and impaired detection of moving objects [23] , [24] . Our results demonstrated analgesic effects of self-generated movement on both sensory and affective dimensions of pain, consistent with a previous study showing that the self-controlled pain was perceived as less intense and anxious than externally controlled pain [25] . Together with the literature, our results suggest that self-generated movement may suppress sensory systems in general and influence the affective dimension along with the sensory dimension of pain.

The current study examined how pain perception is inhibited by voluntary movement. The results confirmed previous findings that self-induced pain is perceived as less intense and unpleasant than externally induced pain. Furthermore, we demonstrated that a large brain network was activated in the externally induced pain state, including the SI and caudate nucleus, which was consistent with previous studies [14] , [21] . In contrast, during self-induced pain, pain-related brain areas including SI, thalamus, ACC and caudate nucleus were deactivated. These results suggest that suppression of the pain-related brain areas may underlie inhibition of pain by self-generated movement.

In fact from a psychological perspective, the impact of self control on pain perception generally differs from that of being controlled. Previous studies have found that the analgesic effects appeared when subjects controlled noxious stimuli themselves [25] , or viewed their pain-receiving hands directly or with a mirror [30] . These effects may be attributed to the emotional reappraisal of pain in such self-related conditions [25] . People with stronger self control or internal locus of control tend to have better performance in various tasks [31] , [32] and be more tolerable to pain [33] . In clinical settings, active exercises and movements have been recommended as part of a comprehensive rehabilitation in patients with chronic pain. Our current results provide evidence that active movements produce less pain and help enhance pain tolerance, supporting the ‘paradoxical pain therapy’ in which patients are encouraged to use their injured body in spite of pain [34] .

In addition to corollary discharge, another possible explanation for the suppression of pain by self-generated movement is the expectation of pain. Subjects in the current experiment engaged in the same movement under self- or externally generated pain conditions, but the expectation of pain was different. Specifically, for self-generated pain, subjects could anticipate quite accurately the time and intensity of the painful stimulation, unlike when pain was externally generated. It is well-accepted that certain expectations result in analgesia [28] while uncertainty can lead to hyperalgesia [29] . Thus, the analgesic effects of self-generated movement in this experiment might result from certain expectation in the self-generated pain condition.

However, the reason for the laterality of such inhibition was still unclear. It was reported that corollary discharges mainly inhibit sensory pathways contralateral to the voluntary movement in higher species [2] , yet an imaging study found that voluntary movement deactivated the ipsilateral SI [19] . In fact, along with the significant deactivation found in the side contralateral to the squeezing right hand, there were scattered and borderline significant deactivation in the ipsilateral side (not reported in the table 1 ) in the present study. Thus it is possible that the active movement inhibited SI in the both hemispheres, yet imposed more sever effects on the contralateral side.

The analgesic effect of voluntary movement may be due to inhibition of the pain matrix in the brain. One possible explanation for this effect is corollary discharge. Studies in the fields of vision, audition and somatosensation have demonstrated that when the central nervous system elicits a movement command, it also sends a copy, or corollary discharge, to inhibit the sensory systems. Similarly, electroencephalographic studies have found that self-generated movement suppressed the pain it induced and inhibited SI activity [15] . Although there is no direct evidence supporting corollary discharge for such inhibition, it is a commonly-accepted theory in the literature, and some researchers theorize that a source of corollary discharges may be cerebellum, from which the corollary discharges are sent to the parietal cortex [16] . Studies using fMRI support this theory by showing that self-generated movement deactivates sensory cortex [19] . Some researchers even speculate that corollary discharge contributes to the formation of the senses [26] , and this view gains support from studies showing that self-generated touches are more likely to lead to object recognition [27] .

Brain networks involved in analgesia during self-generated movement

The fMRI scans revealed two important results. First, many brain areas such as MI and LG that were not pain related showed distinct activation patterns in active and passive pain. This large-scale recruitment of brain regions (e.g., MI, iFG, mFG, AG, LG, caudate) may support the complex processing required by self-generated movement, including cognition, attention, motor planning, and execution. Second, bilateral insula were significantly activated in both the active and passive pain, while only slightly activated in active and passive pressure. This indicates that insula may be specific to stimuli properties and independent of ways of application.

Our results suggest that changes of the SI activity may be responsible for the analgesia induced by self-generated movement. Pharmacological manipulation of corticofugal modulation found that activation of cortical output in the SI enhanced response of the ventral posterior lateral nucleus of thalamus (VPL) to noxious stimulus, while inhibition of this area decreased the VPL activation [35]. Our behavioral study also confirmed that SI can modulate pain, with facilitation of acute pain while inhibition of chronic pain [36]. An electrophysiological study found that electrical stimulation of SI in rats attenuated dorsal horn neuronal response to noxious pinch [37]. Imaging studies discovered that self-generated movement could alleviate pain, possibly through the deactivation in SI, either contralateral [15] or ipsilateral [19] to painful stimulation. Although SI has not been consistently demonstrated to be associated with pain in earlier reports [38], recent imaging studies confirm the role of SI in coding pain intensity. A recent fMRI study found that activation of SI in human subjects was positively correlated with pain intensity [19]. Optical imaging studies also demonstrated that the intensity of optical intrinsic signals which indirectly reflects excitability of neurons in SI was correlated with the intensity of noxious stimulation applied to rats [39],[40]. Our current results showed that, under self-generated pain condition, the intensity of pain was negatively correlated with the BOLD signals of SI. Considering that SI neurons were largely activated by acute painful stimulation [41], and descending information flow greatly increased at this time [42], the SI activation may be the key factor for the perception of acute pain. Thus, the decrease of SI activity observed in the current report may reflect an involvement of this area in the inhibition of active movement-induced pain.

The role of ACC under such active and passive painful conditions is still not clear as apparent inconsistence was found between our results and previous findings. ACC generally contains three parts: perigenual or rostral ACC (rACC), mid ACC (mACC), pACC. For a long time, rACC has been considered to be a classical region in pain processing because it was persistently activated under externally applied painful stimulation. A previous imaging study showed that rACC was activated during pain caused by self-generated movement and deactivated by pain caused by externally generated movement, while pACC showed a reversed pattern, and mACC showed no difference [17]. Wiech et al. also found activation of ACC in the self-generated condition in an fMRI study investigating the neural correlates of analgesia associated with stimulus control [25]. In contrast, we found that rACC was deactivated in active pain and activated in passive pain, and no significant difference was observed in mACC and pACC. The reason for such inconsistency is not clear and may be caused by different ways of stimulus application or different time duration of movement. In the study of Mohr et al, the active movement was used to trigger the onset of the thermal pain stimulation, but with no control on the intensity (i.e., fixed) and duration (terminated by the investigator) of the stimuli. However, in our study, the active movement not only controlled the time course of the stimulation, but also the intensity of it. This makes the pain stimuli more controllable and hence more thoroughly ‘active’ for the subjects. That is probably the reason why our active pain activated less ACC area (no mACC or pACC mobilized) and the rACC were even deactivated. The negative correlation between ACC activation and pain rating further confirmed this finding.

In addition, rACC is part of ventral medial prefrontal cortex which process “self-related” information [43],[44]. Recent studies further support a pivotal role of ACC and PCC in the default mode network, showing activation at rest and deactivation under passive cognitive tasks [45],[46]. Thus, the role of rACC may be quite complicated. We consider that rACC is able to discriminate self and other agents, although the specific activation pattern may not be the same.

Recent studies have suggested that the basal ganglia nuclei, especially the caudate nucleus, might contribute to analgesia in addition to its well-known role in movement, although the pattern of activity is not consistent across studies. The caudate nucleus showed activation when subjects anticipated imminent painful stimuli [47] or tried to suppress pain sensations after pain onset [48],[49]. Conversely, it showed deactivation when the subjects did not try to suppress pain sensations [50]. Studies using acupuncture found that shallow needle punctures deactivated the caudate nucleus while deep punctures activated it [51]. Our results demonstrated that caudate nucleus was deactivated in the self-induced pain condition and activated in the externally induced pain condition. Thus, the caudate nucleus may also be involved in the analgesic effect of self-induced pain.

Previous studies found that vermis were activated in active pain yet less excited than passive pain under normal condition [16], or under thermal hyperalgesia [18]. In our study, correlation analysis of the brain activation with the ratings discovered that vermis was significantly and negatively correlated with the pain or unpleasantness ratings in active pain, but positively correlated with that in passive pain (see Figure 3B). Although cerebellum is mainly in charge of movement execution, subjects made the same movement under active and passive pain conditions in the previous studies [16],[18] and our in study. So the contrast of activities in vermis under active and passive pain unlikely came from movement execution. In our opinion, the less activation in previous studies and the deactivation of the culmen of vermis in our study are probably because that the vermis receives some top-down intervention or cognitive control. Combined with past researches, we consider that culmen of vermis may play a role in analgesia during pain-inducing voluntary movement. The reason that MI was deactivated in active pain is not so clear. Possible explanations may be that MI received inhibition from higher processing areas via motor planning areas [8], or from cerebellum via parietal areas [16],[52].

It was reported that anterior insula showed almost the same activation pattern in both application (active and passive) modes in the previous studies [18],[19]. The present study confirmed this (see Figure 3, fourth row, and Figure 4C), so it is unlikely to be involved in the inhibition of self-generated pain.