Time since onset might be of essence: a recommendation to assess the effects of combination of non-pharmacological neuromodulatory approaches at early stage since symptoms onset

In the past decade researchers began to assess the potential beneficial effects of non-invasive brain stimulation (NIBS) combined with a behavioral task as a treatment approach for various medical conditions. Transcranial direct current stimulation (tDCS) applied to the motor cortex combined with another treatment approach has been assessed as analgesic treatment in neuropathic and non-neuropathic pain conditions, and was found to exert only modest pain relief. Our group results show that combined tDCS and mirror therapy dramatically reduced acute phantom limb pain intensity with long-lasting effects, potentially preventing pain chronification. A review of the scientific literature indicates that our approach differs from that of others: We applied the intervention at the acute stage of the disease, whereas other studies applied the intervention in patients whose disease had already been established. We suggest that the timing of administration of the combined intervention is critical. Unlike in patients with chronic painful condition, in which the maladaptive plasticity associated with pain chronification and chronicity is well-consolidated, early treatment at the acute pain stage may be more successful in counterbalancing the not-yet consolidated maladaptive plasticity. We encourage the research community to test our hypothesis, both in the treatment of pain, and beyond.info:eu-repo/semantics/publishedVersio

Hemispheric Asymmetry in White Matter Connectivity of the Temporoparietal Junction with the Insula and Prefrontal Cortex

The temporoparietal junction (TPJ) is a key node in the brain's ventral attention network (VAN) that is involved in spatial awareness and detection of salient sensory stimuli, including pain. The anatomical basis of this network's right-lateralized organization is poorly understood. Here we used diffusion-weighted MRI and probabilistic tractography to compare the strength of white matter connections emanating from the right versus left TPJ to target regions in both hemispheres. Symmetry of structural connectivity was evaluated for connections between TPJ and target regions that are key cortical nodes in the right VAN (insula and inferior frontal gyrus) as well as target regions that are involved in salience and/or pain (putamen, cingulate cortex, thalamus). We found a rightward asymmetry in connectivity strength between the TPJ and insula in healthy human subjects who were scanned with two different sets of diffusion-weighted MRI acquisition parameters. This rightward asymmetry in TPJ-insula connectivity was stronger in females than in males. There was also a leftward asymmetry in connectivity strength between the TPJ and inferior frontal gyrus, consistent with previously described lateralization of language pathways. The rightward lateralization of the pathway between the TPJ and insula supports previous findings on the roles of these regions in stimulus-driven attention, sensory awareness, interoception and pain. The findings also have implications for our understanding of acute and chronic pains and stroke-induced spatial hemineglect

Aerobic Upper-Limb Exercise-Induced Hypoalgesia: Does It Work?

Background: Aerobic exercise reduces pain sensitivity, a phenomenon known as exercise-induced hypoalgesia (EIH); however, little is known about EIH when the upper limbs are aerobically exercised. This study aimed to test the acute effect of a single aerobic upper-limb exercise on pain threshold and pain intensity in healthy participants, with two different protocols for controlling intensity. Methods: 31 participants performed two 20 min exercise sessions a week apart. In each session, the intensity was controlled by a target heart rate (THR) of 60% of heart rate reserve or by a rate of perceived exertion (RPE) of 7/10 on the Borg scale. Pain threshold for pressure (PPT) heat (HPT) and pain intensity in response to Tonic Heat Pain (THP) were measured pre- and post-exercise. To examine the effect of exercise in each protocol on pain sensitivity, rmANOVA was conducted. Results: Pain sensitivity remained unchanged following arm exercise in both protocols (PPT, p = 0.67; HPT, p = 0.56; and THP p = 0.39). Higher HR in the THR protocol was demonstrated with a significant protocol X time, interaction effect (F(3) = 11.194 p < 0.004). Conclusions: Moderate–high-intensity upper-limb aerobic exercise did not affect pain sensitivity in healthy individuals. Exercise intensity when controlled by THR showed a higher mean heart rate compared to exercise intensity based on RPE

Aerobic Upper-Limb Exercise-Induced Hypoalgesia: Does It Work?

Background: Aerobic exercise reduces pain sensitivity, a phenomenon known as exercise-induced hypoalgesia (EIH); however, little is known about EIH when the upper limbs are aerobically exercised. This study aimed to test the acute effect of a single aerobic upper-limb exercise on pain threshold and pain intensity in healthy participants, with two different protocols for controlling intensity. Methods: 31 participants performed two 20 min exercise sessions a week apart. In each session, the intensity was controlled by a target heart rate (THR) of 60% of heart rate reserve or by a rate of perceived exertion (RPE) of 7/10 on the Borg scale. Pain threshold for pressure (PPT) heat (HPT) and pain intensity in response to Tonic Heat Pain (THP) were measured pre- and post-exercise. To examine the effect of exercise in each protocol on pain sensitivity, rmANOVA was conducted. Results: Pain sensitivity remained unchanged following arm exercise in both protocols (PPT, p = 0.67; HPT, p = 0.56; and THP p = 0.39). Higher HR in the THR protocol was demonstrated with a significant protocol X time, interaction effect (F(3) = 11.194 p Conclusions: Moderate–high-intensity upper-limb aerobic exercise did not affect pain sensitivity in healthy individuals. Exercise intensity when controlled by THR showed a higher mean heart rate compared to exercise intensity based on RPE

Brain-to-brain coupling during handholding is associated with pain reduction

International audienc

Central Sensitization and Psychological State Distinguishing Complex Regional Pain Syndrome from Other Chronic Limb Pain Conditions: A Cluster Analysis Model

Complex regional pain syndrome (CRPS) taxonomy has been updated with reported subtypes and is defined as primary pain alongside other chronic limb pain (CLP) conditions. We aimed at identifying CRPS clinical phenotypes that distinguish CRPS from other CLP conditions. Cluster analysis was carried out to classify 61 chronic CRPS and 31 CLP patients based on evoked pain (intensity of hyperalgesia and dynamic allodynia, allodynia area, and after-sensation) and psychological (depression, kinesiophobia, mental distress, and depersonalization) measures. Pro-inflammatory cytokine IL-6 and TNF-α serum levels were measured. Three cluster groups were created: ‘CRPS’ (78.7% CRPS; 6.5% CLP); ‘CLP’ (64.5% CLP; 4.9% CRPS), and ‘Mixed’ (16.4% CRPS; 29% CLP). The groups differed in all measures, predominantly in allodynia and hyperalgesia (p 0.58). ‘CRPS’ demonstrated higher psychological and evoked pain measures vs. ‘CLP’. ‘Mixed’ exhibited similarities to ‘CRPS’ in psychological profile and to ‘CLP’ in evoked pain measures. The serum level of TNF-αwas higher in the ‘CRPS’ vs. ‘CLP’ (p < 0.001) groups. In conclusion, pain hypersensitivity reflecting nociplastic pain mechanisms and psychological state measures created different clinical phenotypes of CRPS and possible CRPS subtypes, which distinguishes them from other CLP conditions, with the pro-inflammatory TNF-α cytokine as an additional potential biomarker

A dual-brain approach for understanding the neuralmechanisms that underlie the comforting effects of social touch.

Across different cultures, social touch is used to alleviate distress. Here we adopt a dual-brain approach with fMRI to examine whether social touch involves similar activations between the suffering 'target' and the empathizer in brain regions related to emotional sharing such as the observation-execution (mirror) network. To inspect the neural underpinnings of the effects of social touch on pain, we scanned romantic couples during a task that required one partner (the empathizer) to hold the target's hand as the latter experienced painful thermal stimulation. Empathizers and target participants were scanned sequentially, in two counterbalanced phases. Results revealed that hand-holding reduced the pain of the target participant, compared to the severity of pain in a control condition (holding a rubber ball). Importantly, during social touch we found striking shared activations between the target and empathizer in the inferior parietal lobule (IPL), a region related to the observation-execution network. The brain-to-brain analysis further revealed a positive correlation of IPL activation levels between the target and the empathizer. Finally, psychophysiological interaction (PPI) analysis in the target showed that the IPL activity during social touch was positively coupled with activity in the dorsomedial prefrontal cortex, a region that has been implicated in emotion regulation, suggesting that the interaction between the observation-execution network and emotion regulation network may contribute to pain reduction during social touch

Regions of interest, displayed on the MNI152 stereotaxic brain for A) TPJ seeds where tractography was initiated (top row displays seeds for primary analysis, and bottom row displays seeds for secondary analysis) and B) targets.

<p>For targets, the left image displays perigenual anterior cingulate cortex (pgACC) and mid-cingulate cortex (MCC), the middle image displays bilateral pars triangularis of the inferior frontal gyrus (IFGt), pars opercularis of the inferior frontal gyrus (IFGo), putamen and thalamus, and the right image displays the short gyrus of the insula.</p