Tonic pain alters functional connectivity of the descending pain modulatory network involving amygdala, periaqueductal gray, parabrachial nucleus and anterior cingulate cortex.

INTRODUCTION: Resting state functional connectivity (FC) is widely used to assess functional brain alterations in patients with chronic pain. However, reports of FC accompanying tonic pain in pain-free persons are rare. A network we term the Descending Pain Modulatory Network (DPMN) is implicated in healthy and pathologic pain modulation. Here, we evaluate the effect of tonic pain on FC of specific nodes of this network: anterior cingulate cortex (ACC), amygdala (AMYG), periaqueductal gray (PAG), and parabrachial nuclei (PBN). METHODS: In 50 pain-free participants (30F), we induced tonic pain using a capsaicin-heat pain model. functional MRI measured resting BOLD signal during pain-free rest with a 32 °C thermode and then tonic pain where participants experienced a previously warm temperature combined with capsaicin. We evaluated FC from ACC, AMYG, PAG, and PBN with correlation of self-report pain intensity during both states. We hypothesized tonic pain would diminish FC dyads within the DPMN. RESULTS: Of all hypothesized FC dyads, only PAG and subgenual ACC was weakly altered during pain (F = 3.34; p = 0.074; pain-free>pain d = 0.25). After pain induction sACC-PAG FC became positively correlated with pain intensity (R = 0.38; t = 2.81; p = 0.007). Right PBN-PAG FC during pain-free rest positively correlated with subsequently experienced pain (R = 0.44; t = 3.43; p = 0.001). During pain, this connection's FC was diminished (paired t=-3.17; p = 0.0026). In whole-brain analyses, during pain-free rest, FC between left AMYG and right superior parietal lobule and caudate nucleus were positively correlated with subsequent pain. During pain, FC between left AMYG and right inferior temporal gyrus negatively correlated with pain. Subsequent pain positively correlated with right AMYG FC with right claustrum; right primary visual cortex and right temporo-occipitoparietal junction CONCLUSION: We demonstrate sACC-PAG tonic pain FC positively correlates with experienced pain and resting right PBN-PAG FC correlates with subsequent pain and is diminished during tonic pain. Finally, we reveal PAG- and right AMYG-anchored networks which correlate with subsequently experienced pain intensity. Our findings suggest specific connectivity patterns within the DPMN at rest are associated with subsequently experienced pain and modulated by tonic pain. These nodes and their functional modulation may reveal new therapeutic targets for neuromodulation or biomarkers to guide interventions.

Wearable technology in stroke rehabilitation: towards improved diagnosis and treatment of upper-limb motor impairment.

Stroke is one of the main causes of long-term disability worldwide, placing a large burden on individuals and society. Rehabilitation after stroke consists of an iterative process involving assessments and specialized training, aspects often constrained by limited resources of healthcare centers. Wearable technology has the potential to objectively assess and monitor patients inside and outside clinical environments, enabling a more detailed evaluation of the impairment and allowing the individualization of rehabilitation therapies. The present review aims to provide an overview of wearable sensors used in stroke rehabilitation research, with a particular focus on the upper extremity. We summarize results obtained by current research using a variety of wearable sensors and use them to critically discuss challenges and opportunities in the ongoing effort towards reliable and accessible tools for stroke rehabilitation. Finally, suggestions concerning data acquisition and processing to guide future studies performed by clinicians and engineers alike are provided.

Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal).

The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single-neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms.

Dissecting motor skill acquisition: Spatial coordinates take precedence.

Practicing a previously unknown motor sequence often leads to the consolidation of motor chunks, which enable its accurate execution at increasing speeds. Recent imaging studies suggest the function of these structures to be more related to the encoding, storage, and retrieval of sequences rather than their sole execution. We found that optimal motor skill acquisition prioritizes the storage of the spatial features of the sequence in memory over its rapid execution early in training, as proposed by Hikosaka in 1999. This process, seemingly diminished in older adults, was partially restored by anodal transcranial direct current stimulation over the motor cortex, as shown by a sharp improvement in accuracy and an earlier yet gradual emergence of motor chunks. These results suggest that the emergence of motor chunks is preceded by the storage of the sequence in memory but is not its direct consequence; rather, these structures depend on, and result from, motor practice.

During capsaicin-induced central sensitization, brush allodynia is associated with baseline warmth sensitivity, whereas mechanical hyperalgesia is associated with painful mechanical sensibility, anxiety and somatization.

BACKGROUND: Mechanical hyperalgesia and allodynia incidence varies considerably amongst neuropathic pain patients. This study explored whether sensory or psychological factors associate with mechanical hyperalgesia and brush allodynia in a human experimental model. METHODS: Sixty-six healthy volunteers (29 male) completed psychological questionnaires and participated in two quantitative sensory testing (QST) sessions. Warmth detection threshold (WDT), heat pain threshold (HPT) and suprathreshold mechanical pain (STMP) ratings were measured before exposure to a capsaicin-heat pain model (C-HP). After C-HP exposure, brush allodynia and STMP were measured in one session, whilst mechanical hyperalgesia was measured in another session. RESULTS: WDT and HPT measured in sessions separated by 1 month demonstrated significant but moderate levels of reliability (WDT: ICC = 0.5, 95%CI [0.28, 0.77]; HPT: ICC = 0.62, 95%CI [0.40, 0.77]). Brush allodynia associated with lower WDT (z = -3.06, p = 0.002; ϕ = 0.27). Those with allodynia showed greater hyperalgesia intensity (F = 7.044, p = 0.010, ηp 2  = 0.107) and area (F = 9.319, p = 0.004, ηp 2  = 0.163) than those without allodynia. No psychological self-report measures were significantly different between allodynic and nonallodynic groups. Intensity of hyperalgesia in response to lighter mechanical stimuli was associated with lower HPT, higher STMP ratings and higher Pain Sensitivity Questionnaire scores at baseline. Hyperalgesia to heavier probe stimuli associated with state anxiety and to a lesser extent somatic awareness. Hyperalgesic area associated with lower baseline HPT and higher STMP ratings. Hyperalgesic area was not correlated with allodynic area across individuals. CONCLUSIONS: These findings support research in neuropathic pain patients and human experimental models that peripheral sensory input and individual sensibility are related to development of mechanical allodynia and hyperalgesia during central sensitization, whilst psychological factors play a lesser role. SIGNIFICANCE: We evaluated differential relationships of psychological and perceptual sensitivity to the development of capsaicin-induced mechanical allodynia and hyperalgesia. Fifty percent of healthy volunteers failed to develop mechanical allodynia. Baseline pain sensitivity was greater in those developing allodynia and was related to the magnitude and area of hyperalgesia. State psychological factors, whilst unrelated to allodynia, were related to mechanical hyperalgesia. This supports that the intensity of peripheral sensory input and individual sensibility are related to development of mechanical allodynia and hyperalgesia during central sensitization, whilst psychological factors play a lesser role.

Pain reduction due to novel sensory-motor training in Complex Regional Pain Syndrome I - A pilot study.

BACKGROUND AND AIMS: Patients suffering from Complex Regional Pain Syndrome (CRPS) of the upper limb show a changed cortical representation of the affected hand. The lip area invades the former hand area contralateral to the affected hand. This change in cortical representation is correlated to the intensity of ongoing pain in patients with CRPS. Further studies revealed that restoration of the original representation coincides with a decrease of pain. Sensory-motor training protocols can increase and/or relocate cortical somatosensory and motor representation areas of the fingers, as shown, for example, in Braille reading individuals and professional violin players. Further, there is evidence that sensory-motor discrimination training has a beneficial effect on both the intensity of pain and the mislocalization of sensory-motor cortical areas in CRPS patients. Based on these propositions, we developed a novel sensory-motor self-training paradigm for CRPS patients to use in a home-based manner. METHODS: Ten CRPS patients performed the sensory-motor training for 2weeks. The training consists of a braille-like haptic task with different training modes (bi-manual, speed and memory training). During the training, as well as 1week before and after, patients were asked to fill out pain diaries. Furthermore, measures of impairment were acquired at baseline and post training. RESULTS: Patients showed significant pain reduction after the 2week training period. The overall disability as well as the depression scores showed a trend to improve after the 2week training. The reduction in pain was correlated with the total amount of training performed. CONCLUSIONS: This is a first proof of principle study of a novel sensory-motor self-training protocol to reduce pain in CRPS patients. The more consistent the patients trained the larger the pain reduction. Sensory-motor training, which can be performed on a regular basis at home might provide a novel interventional strategy to improve symptoms of CRPS. IMPLICATIONS: Although a larger study needs to be conducted to confirm our findings, including long-term follow-up, the results show, that a sensory-motor home-based training is a strategy worth exploring further for the reduction of pain as well as high frequency training for patients with CRPS.