Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by disproportionate pain to the original injury accompanied by sensory, motor and autonomic dysfunctions (Harden et al., 2007). In this population, sensory disturbances are frequently observed and are characterized by changes in the perception of limb weight and temperature, a distorted mental image of the affected limb, feeling the limb as a foreign body part with a pronounced disliking and a desire to amputate it (Förderreuther et al., 2004; Lewis et al., 2007). It is important to note that sensory disturbances are also observed in other chronic pain conditions, but are clearly more pronounced in CRPS (Förderreuther et al., 2004; Frettlöh et al., 2006), and occur mainly in the affected limb (Lewis et al., 2007). In parallel, several studies demonstrates that sensory deficits (changes in sensation, i.e. the stimulus detection by the sensory system) measured with quantitative sensory testing (as hyperalgesia, hyperesthesia, etc.) extend beyond the affected limb (Rommel et al., 2001; Drummond et al., 2018; Palmer et al., 2019), but this has not been investigated for sensory disturbances (changes in perception, i.e. the interpretation/the meaning of the sensory stimuli). Moreover, the reasons why people with CRPS report such sensory disturbances still remain unclear.

It has been shown that sensory disturbances are positively associated with anxiety and pain-catastrophizing (Michal et al., 2017), and some authors suggested that CRPS represents an excessive response to perceived threat of tissue injury (Bean et al., 2015). Considering the fact that a perceived threat leads to attentional bias in anxiety disorders (Cisler and Koster, 2010), it has been suggested that sensory disturbances are due to attentional effects (Förderreuther et al., 2004; Frettlöh et al., 2006; Michal et al., 2017).

Other theories suggest that CRPS sensory disturbances are explained by cortical reorganizations (McCabe and Blake, 2008) that are observed in the primary somatosensory (Di Pietro et al., 2013) and motor (Maihöfner et al., 2003) cortices, and in the posterior parietal cortex (Vartiainen et al., 2009). These cortical reorganizations might affect sensorimotor integration since the motor command and the related sensory feedback are closely coupled to monitor movements. It has been hypothesized that sensory disturbances, including painful sensations, are due to an incongruence between the predicted and the actual sensory feedback, named as sensorimotor conflict (Harris, 1999; McCabe et al., 2009). To demonstrate that point, numerous studies experimentally created sensorimotor conflicts. Such conflicts have been shown to induce sensory disturbances in various pain populations (Don et al., 2016), including in CRPS (Brun et al., 2018c). These sensory disturbances are qualitatively similar to the sensory disturbances that are spontaneously (i.e., in the absence of experimental manipulation) reported by the patients (McCabe et al., 2007).

If sensory disturbances are explained by cortical reorganization and sensorimotor integration deficits rather than by attentional factors, they would be expected to be specific in terms of the category of sensation evoked and in terms of localization. Attentional factors such as arousal or hypervigilance could result in more general and diffuse effects, for example effects relative to other sensory domains (visual, hearing, smelling, etc.) and beyond the affected body part (McDermid et al., 1996). In CRPS, higher discomfort also extends to auditory stimuli (Knudsen et al., 2011). Recent studies identified two distinct categories of sensory disturbances evoked by sensorimotor conflict (Category 1: pain, discomfort, lost limb, temperature, weight; Category 2: peculiarity, losing control, extra-limb) that are differentially affected by the presence of pain (Brun et al., 2017; Brun et al., 2018c). Indeed, conflict-induced Category 1 disturbances are more intense in people with CRPS and fibromyalgia syndrome compared to pain-free individuals, while conflict-induced Category 2 disturbances do not differ between groups. This specificity, in the pattern of sensations evoked, suggests that sensory disturbances arise from sensorimotor processes rather than from attentional effects. Another way of addressing the specificity of the sensory disturbances evoked by conflicts would be to compare sensory disturbances evoked in a painful vs. non-painful site. This has not been done so far as previous studies were either conducted using a mirror (involving both upper or lower limbs) (Don et al., 2016) or using virtual reality (which provide much more flexible ways of inducing a conflict during unilateral movement) but in a population with generalized pain (fibromyalgia) (Brun et al., 2020).

Therefore, the first objective of the study was to assess whether sensory disturbances evoked by a unilateral sensorimotor conflict are specific to the painful limb and differ according to the Category of sensory disturbances in individuals with a unilateral CRPS compared to healthy controls (HC). We hypothesized that CRPS participants would report higher Category 1 disturbances than Category 2 for the Affected limb, and that a reverse pattern (Category 2 disturbances > Category 1 disturbances) would be observed for the Unaffected limb and HC, based on results of previous studies (Brun et al., 2017; Brun et al., 2018c).

A second objective was to assess the association between clinical characteristics and sensory disturbances evoked by a unilateral sensorimotor conflict. Clinical characteristics considered included the intensity and duration of pain, proprioception deficits, and body perception disturbances.

A third objective was to assess motor disturbances induced by a unilateral sensorimotor conflict as several studies showed increased motor disturbances during sensorimotor conflicts (Brun et al., 2017; Brun et al., 2020) and motor impairments in CRPS (Maihöfner et al., 2003; Bank et al., 2013). We hypothesized that motor disturbances induced by the conflict would be higher for the Affected limb compared to the Unaffected limb and HC.

The origin of sensory disturbances in CRPS still remains unclear and it has been suggested that attentional and/or sensorimotor integration deficits are involved. In this study, we assessed whether sensory disturbances evoked by a unilateral sensorimotor conflict are specific to the Affected limb and differ according to the Category of sensory disturbances in individuals with a unilateral CRPS and HC. Our results demonstrate that CRPS participants report higher Category 1 than Category 2 disturbances for the Affected limb (while the reverse was observed for HC and for the Unaffected side). In addition, no difference was observed between the Unaffected limb in CRPS and the Dominant limb in HC for Category 2 disturbances, while higher conflict sensitivity was observed for Category 1 disturbances. Conflict sensitivity was related to higher pain (but not to other clinical characteristics) only for Category 1 disturbances. This pattern of results is better aligned with the sensorimotor integration hypothesis than with the hypothesis of a hypervigilance toward sensory disturbances since conflict sensitivity in CRPS is specific to Category 1 disturbances and to the Affected limb. However, the lack of intra- or inter-group difference in the motor disturbances evoked by the conflict somehow challenges the idea of sensorimotor integration deficits.

The uncertainty of results for deficits in sensorimotor integration in CRPS is well summarized in Bultitude and Petrini’s study (Bultitude and Petrini, 2021). As noted by the authors, while alteration in body perception (Förderreuther et al., 2004; Lewis et al., 2007; Lewis and Schweinhardt, 2012) and motor performance (Maihöfner et al., 2003; Bank et al., 2014) are frequently observed in this population, some studies have failed to demonstrate deficits in sensorimotor integration (Turton et al., 2007; Reinersmann et al., 2013; Wang et al., 2019). However, these studies did not require active movements from the participants, which is a strong limitation to study sensorimotor integration. A very few studies have investigated sensorimotor integration during active movements in CRPS and focus either on sensory perception (Brun et al., 2018b; Brun et al., 2018c), motor performance (Verfaille et al., 2020; Bultitude and Petrini, 2021) or both (Tajadura-Jiménez et al., 2017). Results of these studies have consistently shown alterations in perception, while alterations in motor performance are inconsistent across studies. For sensory perception, our results replicate a previous study showing that individuals with CRPS and fibromyalgia are more sensitive to sensorimotor conflicts, specifically for Category 1 sensory disturbances (i.e., items related to an increase of pain, discomfort, a change in weight and temperature, and the feeling of losing a limb) compared to pain-free individuals and people with arthritis (Brun et al., 2018c). Moreover, the sense of limb movement during active movements is altered in CRPS and is characterized by blurred representation of the movement’s limb (Brun et al., 2018b). Another study investigated integration of auditory stimuli during walking and demonstrated that real-time alterations of the sound produced by walking increase body perception disturbances and pain in CRPS (Tajadura-Jiménez et al., 2017), and this effect seems to be larger and more variable than the previously described effect in healthy individuals (Tajadura-Jiménez et al., 2015). In addition to these sensory perturbations, altered gait biomechanics (stance and swing) was observed during these alterations of auditory feedback, but this effect appeared to be similar for CRPS and healthy individuals (Tajadura-Jiménez et al., 2015; Tajadura-Jiménez et al., 2017). Two other studies investigated sensorimotor integration during active movements with measures of motor performance in CRPS participants compared to controls (Verfaille et al., 2020; Bultitude and Petrini, 2021). Verfaille and collaborators demonstrated that CRPS participants make more errors than controls during a reaching task that requires the participant to integrate visual and proprioceptive feedback. Interestingly, this increase in errors was not explained by isolated deficits in visual or proprioceptive processing, but rather by a difficulty to integrate both sources of information during movement (Verfaille et al., 2020). However, Bultitude and Petrini found that people with CRPS can optimally integrate visual and self-motion cues under some conditions, but use different strategies to controls (Bultitude and Petrini, 2021). Overall, it appears that sensory perturbations arising from sensorimotor integration problems in CRPS do not necessarily result in deficits in motor performance, a result that was also found in fibromyalgia (Brun et al., 2020) and in healthy individuals with experimental pain (Brun et al., 2017), potentially due to adaptations in motor strategies employed.

While our results suggest deficits in sensorimotor integration, it is not possible to totally exclude the attentional hypothesis. Attentional bias in chronic pain might be expressed in hypervigilance toward the pain and pain-related information (Hollins et al., 2009), and/or a bias away from the painful limb (Broadbent et al., 2021). Spatial neglect has been well studied in CRPS (for a systematic review and meta-analysis see (Broadbent et al., 2021)), but hypervigilance for pain and other pain-related information in CRPS was poorly investigated (Broadbent et al., 2021). In our study, higher Category 1 sensations for the Unaffected limb were observed in CRPS compared to HC, which suggests hypervigilance toward Category 1 disturbances in CRPS. However, the fact that higher Category 1 disturbances are observed for the Affected limb compared to the Unaffected limb in CRPS suggest that hypervigilance cannot completely explain sensory disturbances in CRPS.

Some limitations need to be highlighted. A convenience sample was used and a small number of participants was recruited in the CRPS group, yielding the possibility of type II error. Note however that nparLD analyses are well designed for small sample sizes. Difficulty in recruitment was explained by the choice of the experimental set-up (KINARM exoskeleton system). First, this system requires the participants to be positioned with 80° of shoulder abduction while performing forward movements (in the horizontal plane) of 30 cm (the UL being fully supported by the exoskeleton). This limits the inclusion of participants with shoulder deficits. Second, participants with a body mass index superior to 30 can typically not be appropriately fitted in the KINARM, also leading to the exclusion of some participants. These limitations both tend to bias the sample toward individuals with milder CRPS. Despite this, significant differences were observed for sensory disturbances. However, this might contribute to the absence of significant results for motor disturbances. In addition, the effects of treatments (pharmacological and non-pharmacological) have not been controlled and might interfere with the results. Finally, the affected limb of CRPS participants was compared to the nondominant limb of the controls, irrespective of the hand dominance of the CRPS participants. This approach, although commonly used in the literature, presents some limitations. However, given the absence of significant difference between both UL and HC, it appears unlikely that this approach has influenced the results.

In conclusion, a unilateral sensorimotor conflict induces higher Category 1 sensory disturbances in the Affected limb compared to both the Unaffected limb in CRPS and the Non-Dominant limb in HC. Therefore, conflict-induced sensory disturbances are specific in terms of the Category of sensation evoked and in terms of localization, suggesting that sensory disturbances in CRPS depend on sensorimotor integration deficits rather than hypervigilance toward pain and pain-related information. However, motor disturbances were similar between CRPS and HC, which suggests that the motor response to the sensorimotor conflict is not impaired. Future work should evaluate the effect of interventions on sensory disturbances in CRPS, to determine whether they disappear in patients who recover.