State of the art in EEG signal features of mindfulness-based treatments for chronic pain

According to the revised International Association for the Study of Pain (IASP) definition [1], pain is ”an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”. When it persists or recurs for more than 3 months, it is classified as chronic. Around 20% of the world’s population suffers from chronic pain (CP), which is associated with psychological, biological or social factors. The IASP classification of CP [2], included in the 11th edition of International Statistical Classification of Diseases (ICD-11) [3], distinguishes between primary and secondary CP. Primary CP is the direct symptom of a condition, e.g. fibromyalgia, chronic migraine or nonspecific low-back pain; secondary CP is characterized by symptoms that originate from another primary disease, e.g. chronic cancer pain, or sequelae of traumas [4].

CP management requires a multimodal approach, which incorporates pharmacological and non-pharmacological treatments [5, 6]. The latter include psychological interventions to support patients in coping with CP-related difficulties, by enabling managing the factors that hinder daily functions, exacerbate discomfort, and amplify painful experiences [7]. Mindfulness-based interventions target the cognitive, affective, and sensory dimensions of pain by cultivating an awareness of the present moment without judgment [8], and are currently used for the treatment of pain in several contexts [9]. The Mindfulness-Based Stress Reduction (MBSR) is an 8-week structured group program (one session per week of 2.5 hours). The goal is to teach patients a new approach to managing their illness, emphasizing self-regulation of pain and negative emotions to enhance their sense of control. The program is used for various CP conditions and positively impacts stress, depression and anxiety [10]. Mindfulness-Based Cognitive Therapy (MBCT), consists of 8 weekly sessions, 2 hours each. It combines principles from Cognitive Therapy and Mindfulness Meditation, with the aim to increase awareness of cognitions, fostering a mindful and accepting approach [11]. Mindfulness Based Pain Management (MBPM) [12] consists of a total of 20 hours of training, spread over 8 weeks, with each session lasting 2.5 hours. The MBPM program instructs participants to engage in Mindfulness training to disrupt the reactive pain cycle that exacerbates physical and emotional stress. Participants cultivate the practice of ’breathing into’ difficult experiences to reduce resistance to pain and release tension.

Recent technology advancements (Extended reality, wearable sensors, etc.) pro- vide insights to enrich and potentiate Mindfulness-based therapeutic practice. The user can immerse himself in a simulated environment that can be customized. Virtual Reality (VR) can be exploited to implement an adaptive experience with the use of biofeedback, leading to greater concentration toward the present moment. In addition, the VR environment allows the subjects to immerse themselves in any scenario while remaining in the clinical or home setting. VR has been found to reduce levels of anxiety, stress, depression and CP by increasing user engagement [13]. Therefore, it could lead to successful Mindfulness practice. The exploitation of EEG signals monitoring during Mindfulness treatment opens new opportunities for real-time therapy personalization. Neurocorrelates of Mindfulness were widely studied in the literature [14, 15]. A review targeting Mindfulness, pain and their neurocorrelates [8] found that somatosensory regions were more activated in expert meditators than in novices, whereas a lower activity of cognitive-affective regions (e.g., prefrontal region) was present, which in novices was less evident. This suggests a potential dissociation between the cognitive-affective and sensory dimensions of pain in experienced meditators. Moreover, an increased modulation of alpha power occurred in expert meditators in order to suppress the sensory input processing. The increased activity in the secondary somatosensory cortex (S2) and posterior insula during meditation compared with rest in experts could reflect increased attention toward bodily sensations and decreased unpleasantness of pain. In contrast, decreased activity in the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) in expert meditators could reflect greater emotional control of painful stimuli. A lower pain ratings in both classes of meditators, as compared to the control class, was also reported in several studies cited. Structural and functional changes, such as increased S2 thickness and increased parietal alpha power during painful stimuli, were prevalent in experienced meditators, which were not found in novice meditators. Wang’s review investigated the short and long-term effects of Mindfulness meditation on pain-related brain processes by comparing the neural activities in beginners and experts meditators [8], and also it focused on multimodal approaches, including both EEG/EMG monitoring and the use of brain imaging through magnetic resonance (MRI/fMRI).

Specifically, experienced meditators showed an increased thickness of the somatosensory cortex and dorsal anterior cingulate cortex (dACC), linked to superior pain tolerance. In addition, they showed less activation in prefrontal regions and more activation in somatosensory regions during meditation. What clearly emerged from these studies is that Mindfulness practices provides greater control over pain processing, promoting relaxation states and less tension, as evidenced by an increase in alpha wave power in the parietal and occipital regions, as well as brain restructuring (e.g. increased thickness), which also allowed for a reduction in the impact of CP on emotions. Indeed, the difference in activation or deactivation of brain areas between experienced and novice meditators indicates effective neuroplasticity promoted by Mindfulness practice. In fact, somatosensory or cognitive-affective areas are also associated with pain processing and modulation of painful sensations [16]. The study in [16] refers to a “pain matrix”, identified as a brain network related to pain processing, and it includes: somatosensory cortices and thalamus associated with the localization of pain, and discrimination of its intensity whereas, the insula and anterior cingulate cortex are related to the emotional aspects and attention toward pain. The joint activation of these regions was found to underlie conscious perception, attentional modulation and control [17]. Furthermore, the pain matrix was considered to reflect a system that brings attention toward the occurrence of a specific sensory event which leads to reaction to a possible danger, not only, therefore, capable of transforming painful sensory input into pain conscious perception [18]. This could be the foundation of a reassessment of the painful stimulus and a remodulation of the focus on the event associated with it through the practice of mindfulness. Nevertheless, the specific and unique association between painful stimuli and the brain areas defining the pain matrix is still debated in the literature, as these areas are also associated with other cognitive processing, and the function of different regions depends on the context in which the stimuli are provided [17, 19,20,21]. In [16], several studies are reported highlighting the neuroplasticity of precisely these areas of the brain by long-term meditation. In particular, an increase in cortical thickness was found mainly in the primary and secondary somatosensory cortex, prefrontal cortex, posterior parietal cortex, temporal gyrus, anterior cingulate cortex, and hippocampus, with increased connectivity between the posterior cingulate cortex, prefrontal cortex, and hippocampus, suggesting an increase in neuronal volume in these regions, which probably contributes to improved cognitive and emotional processing. An increased gray matter volume was found in areas related to emotion regulation and pain processing, such as the hippocampus, amygdala, and thalamus, but even, for instance, in the orbitofrontal cortex and posterior parietal cortex. Also, an improved anatomical connectivity of the white matter was observed, suggesting increased efficiency in neural connections. In addition, experienced meditators showed less pain anticipatory activity in the amygdala and exhibited faster neural habitation in response to pain in the mid-cingulate cortex by analyzing the blood-oxygen-level-dependent (BOLD) signal, probably resulting from a reduction in the emotional impact of anticipation of pain.

Thus, variations in the CP neurophysiology are related to changes in brain’s functional and structural characteristics. CP also leads to changes in the neural networks involved in pain modulation. The dual nature of CP (emotional and sensory) results in a relationship between pain and the mechanisms of somatosensory areas on one side, and between pain and the affective and cognitive mechanisms of other areas on the other side. For instance, nocebo hyperalgesia is an effect of increased intensity of perceived pain caused by anticipatory pain anxiety, promoting a release of cholecystokinin and pain transmission [22]. For this reason, the dissociation of CP related to sensory pain from that due to anxious or depressive states remains quite complex to achieve. An examination of the neurophysiological changes in CP, employing Mindfulness, would be useful to test the plasticity of “actual or potential tissue damage” and/or brain-level reprocessing of a response to the painful insult. Although clinical evidence exists for the effectiveness of Mindfulness in reducing pain perception or frequency (e.g [23]) EEG-based analyses regarding the efficacy of Mindfulness treatments in CP are currently lacking.

Hence the need for a review that focuses on a specific and detailed analysis of changes in EEG features related to pain in response to Mindfulness interventions in.

individuals with CP. Therefore, the aim of this review is to investigate EEG features related to objective effects on CP produced by Mindfulness-based treatments. In this regard, the results of studies on EEG related to Mindfulness-based treatment for CP are described and assessed.

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