Impact of Chronic Pain on Use-Dependent Plasticity: Corticomotor Excitability and Motor Representation in Musicians With and Without Pain.

Long-term musical training induces adaptive changes in the functional representation of the motor cortex. It is unknown if the maladaptive plasticity associated with chronic pain, frequently affecting trained musicians, may alter the use-dependent plasticity in the motor cortex. This study investigated the interaction between adaptive and maladaptive plasticity in the motor pathways, in particular how chronic pain influences long-term use-dependent plasticity. Using transcranial magnetic stimulation (TMS), corticospinal excitability was assessed by measuring the amplitude of the motor-evoked potential (MEP), area of the motor map, volume, and center of gravity of the first dorsal interosseous muscle in 19 pain-free musicians, 17 upper limb/neck pain chronic pain musicians, and 19 pain-free non-musicians as controls. Motor map volume and MEP amplitude were smaller for both pain-free and chronic pain musicians compared to pain-free controls (P < 0.011). No significant differences were found between musicians with and without chronic pain. These findings confirm that long-term musical training can lead to focalized and specialized functional organization of the primary motor cortex. Moreover, the adaptive use-dependent plasticity acquired through fine-motor skill acquisition is not significantly compromised by the maladaptive plasticity typically associated with chronic pain, highlighting the potential of long-term sensorimotor training to counteract the effects of chronic pain in the motor system.

Experience-dependent neuroplasticity in trained musicians modulates the effects of chronic pain on insula-based networks - A resting-state fMRI study.

Recent resting-state fMRI studies associated extensive musical training with increased insula-based connectivity in large-scale networks involved in salience, emotion, and higher-order cognitive processes. Similar changes have also been found in chronic pain patients, suggesting that both types of experiences can have comparable effects on insula circuitries. Based on these observations, the current study asked the question whether, and if so in what way, different forms of experience-dependent neuroplasticity may interact. Here we assessed insula-based connectivity during fMRI resting-state between musicians and non-musicians both with and without chronic pain, and correlated the results with clinical pain duration and intensity. As expected, insula connectivity was increased in chronic pain non-musicians relative to healthy non-musicians (with cingulate cortex and supplementary motor area), yet no differences were found between chronic pain non-musicians and healthy musicians. In contrast, musicians with chronic pain showed decreased insula connectivity relative to both healthy musicians (with sensorimotor and memory regions) and chronic pain non-musicians (with the hippocampus, inferior temporal gyrus, and orbitofrontal cortex), as well as lower pain-related inferences with daily activities. Pain duration correlated positively with insula connectivity only in non-musicians, whereas pain intensity exhibited distinct relationships across groups. We conclude that although music-related sensorimotor training and chronic pain, taken in isolation, can lead to increased insula-based connectivity, their combination may lead to higher-order plasticity (metaplasticity) in chronic pain musicians, engaging brain mechanisms that can modulate the consequences of maladaptive experience-dependent neural reorganization (i.e., pain chronification).

Insula-based networks in professional musicians: Evidence for increased functional connectivity during resting state fMRI.

Despite considerable research on experience-dependent neuroplasticity in professional musicians, detailed understanding of an involvement of the insula is only now beginning to emerge. We investigated the effects of musical training on intrinsic insula-based connectivity in professional classical musicians relative to nonmusicians using resting-state functional MRI. Following a tripartite scheme of insula subdivisions, coactivation profiles were analyzed for the posterior, ventral anterior, and dorsal anterior insula in both hemispheres. While whole-brain connectivity across all participants confirmed previously reported patterns, between-group comparisons revealed increased insular connectivity in musicians relative to nonmusicians. Coactivated regions encompassed constituents of large-scale networks involved in salience detection (e.g., anterior and middle cingulate cortex), affective processing (e.g., orbitofrontal cortex and temporal pole), and higher order cognition (e.g., dorsolateral prefrontal cortex and the temporoparietal junction), whereas no differences were found for the reversed group contrast. Importantly, these connectivity patterns were stronger in musicians who experienced more years of musical practice, including also sensorimotor regions involved in music performance (M1 hand area, S1, A1, and SMA). We conclude that musical training triggers significant reorganization in insula-based networks, potentially facilitating high-level cognitive and affective functions associated with the fast integration of multisensory information in the context of music performance. Hum Brain Mapp 38:4834-4849, 2017. © 2017 Wiley Periodicals, Inc.

Facilitation of Early and Middle Latency SEP after tDCS of M1: No Evidence of Primary Somatosensory Homeostatic Plasticity.

Homeostatic plasticity is a mechanism that stabilizes cortical excitability within a physiological range. Most homeostatic plasticity protocols have primed and tested the homeostatic response of the primary motor cortex (M1). This study investigated if a homeostatic response could be recorded from the primary sensory cortex (S1) after inducing homeostatic plasticity in M1. In 31 healthy participants, homeostatic plasticity was induced over M1 with a priming and testing block of transcranial direct current stimulation (tDCS) in two different sessions (anodal and cathodal). S1 excitability was assessed by early (N20, P25) and middle-latency (N33-P45) somatosensory evoked potentials (SEP) extracted from 4 electrodes (CP5, CP3, P5, P3). Baseline and post-measures (post-priming, 0-min, 10-min, and 20-min after homeostatic induction) were taken. Anodal M1 homeostatic plasticity induction significantly facilitated the N20-P25, P45 peak, and N33-P45 early SEP components up to 20-min post-induction, without any indication of a homeostatic response (i.e., reduced SEP). Cathodal homeostatic induction did not induce any significant effect on early or middle latency SEPs. M1 homeostatic plasticity induction by anodal stimulation protocol to the primary motor cortex did not induce a homeostatic response in SEPs.

Multifocal tDCS Targeting the Motor Network Modulates Event-Related Cortical Responses During Prolonged Pain.

Multifocal transcranial direct current stimulation (tDCS) targeting several brain regions is promising for inducing cortical plasticity. It remains unknown whether multifocal tDCS aimed at the resting-state motor network (network-tDCS) can revert N2-P2 cortical responses otherwise attenuated during prolonged experimental pain. Thirty-eight healthy subjects participated in 2 sessions separated by 24 hours (Day1, Day2) of active (n = 19) or sham (n = 19) network-tDCS. Experimental pain induced by topical capsaicin was maintained for 24 hours and assessed using a numerical rating scale. Electrical detection and pain thresholds, and N2-P2 evoked potentials (electroencephalography) to noxious electrical stimulation were recorded before capsaicin-induced pain (Day1-baseline), after capsaicin application (Day1-post-cap), and after 2 sessions of network-tDCS (Day2). Capsaicin induced moderate pain at Day1-post-cap, which further increased at Day2 in both groups (P = .01). Electrical detection/pain thresholds did not change over time. N2-P2 responses were reduced on Day1-post-cap compared to Day1-baseline (P = .019). At Day2 compared with Day1-post-cap, N2-P2 responses were significantly higher in the Active network-tDCS group (P<.05), while the sham group remained inhibited. These results suggest that tDCS targeting regions associated with the motor network may modulate the late evoked brain responses to noxious peripheral stimulation otherwise initially inhibited by capsaicin-induced pain. PERSPECTIVE: This study extends the evidence of N2-P2 reduction due to capsaicin-induced pain from 30 minutes to 24 hrs. Moreover, 2 sessions of tDCS targeting the motor network in the early stage of nociceptive pain may revert the inhibition of N2-P2 associated with capsaicin-induced pain.

Extensive sensorimotor training enhances nociceptive cortical responses in healthy individuals.

BACKGROUND: Prolonged and repeated sensorimotor training is a crucial driver for promoting use-dependent plasticity, but also a main risk factor for developing musculoskeletal pain syndromes, yet the neural underpinnings that link repetitive movements to abnormal pain processing are unknown. METHODS: Twenty healthy musicians, one of the best in vivo models to study use-dependent plasticity, and 20 healthy non-musicians were recruited. Perceptual thresholds, reaction times (RTs) and event-related potentials (ERPs) were recorded using nociceptive intra-epidermal and non-nociceptive transcutaneous electrical stimulation. RESULTS: In response to comparable stimulus intensities, musicians compared to non-musicians showed larger non-nociceptive N140 (associated with higher activation of regions within the salience network), higher nociceptive N200 ERPs (associated with higher activation of regions within the sensorimotor network) and faster RTs to both stimuli. Non-musicians showed larger non-nociceptive P200 ERP. Notably, a similar P200 component prominently emerged during nociceptive stimulation in non-musicians. Across participants, larger N140 and N200 ERPs were associated with RTs, whereas the amount of daily practice in musicians explained non-nociceptive P200 and nociceptive P300 ERPs. CONCLUSIONS: These novel findings indicate that the mechanisms by which extensive sensorimotor training promotes use-dependent plasticity in multisensory neural structures may also shape the neural signatures of nociceptive processing in healthy individuals. SIGNIFICANCE: Repetitive sensorimotor training may increase the responsiveness of nociceptive evoked potentials. These novel data highlight the importance of repetitive sensorimotor practice as a contributing factor to the interindividual variability of nociceptive-related potentials.

Extensive Sensorimotor Training Predetermines Central Pain Changes During the Development of Prolonged Muscle Pain.

Repetitive movements (RM) are a main risk factor for musculoskeletal pain, which is partly explained by the overloading of musculoskeletal structures. However, RM may also drive brain plasticity, leading to maladaptive changes in sensorimotor areas and altered pain processing. This study aimed to understand whether individuals performing extensive RM (musicians) exhibit altered brain processing to prolonged experimental muscle pain. Nineteen healthy musicians and 20 healthy nontrained controls attended 3 sessions (Day 1-Day 3-Day 8). In each session, event-related potentials (ERPs) to non-nociceptive superficial and nociceptive intraepidermal electrical stimulation, reaction times, electrical detection thresholds, and pressure pain thresholds (PPTs) were recorded. In all participants, prolonged muscle pain was induced by intramuscular injection of nerve growth factor (NGF) into the right first dorsal interosseous muscle at the end of Day1. Pain intensity was assessed on a numerical rating scale (NRS) and was lower in musicians compared to non-musicians (P < .007). Moreover, in musicians, the higher amount of weekly training was associated with lower NRS pain scores on Day 3 to Day 8 (P < .037). Compared with Day1, NGF reduced PPTs on Day 3 to Day 8 (P < .001) and non-nociceptive P200 and P300 ERP amplitudes on Day 8 (P < .044) in both groups. Musicians compared to controls showed secondary hyperalgesia to electrical stimulation on Day 3 to Day 8 (P < .004) and reduced nociceptive P200 ERP amplitudes on Day 8 (P < .005). Across participants, ERP components correlated with pain detection reaction times, sensitivity (PPTs and electrical detection thresholds), and severity (NRS), (all P < .043). These results show that repetitive sensorimotor training leads to brain changes in the processing of prolonged pain, biasing the cortical response to nociceptive inputs. PERSPECTIVE: Repetitive sensorimotor training may increase the responsiveness of nociceptive inputs during the development of prolonged muscle pain. These novel data highlight the role of repetitive sensorimotor practice as a source for interindividual variability in central pain processing.

Effects of multifocal transcranial direct current stimulation targeting the motor network during prolonged experimental pain.

BACKGROUND: Antinociceptive effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) have been extensively studied in the past years. However, M1 does not work in isolation, but it rather interacts within a network, the so-called resting-state motor network. OBJECTIVE: To explore the anti-nociceptive effects of a new multifocal tDCS approach administered to regions linked to the resting state motor network (network-tDCS) compared to sham tDCS. METHODS: Healthy individuals were included in this randomized, parallel and double-blinded study comprising two consecutive interventions with 24-hr interval of either active (n = 19) or sham (n = 19) network-tDCS. Prolonged pain was induced by application of topical capsaicin on the dorsum of the hand during a 24-hr period. Assessments of corticomotor excitability (transcranial magnetic stimulation), pain ratings (numerical rating scale, NRS), skin pain sensitivity on the arm (heat and mechanical), temporal summation of pain (TSP) and conditioned pain modulation (CPM) were performed at baseline (Day1-baseline), after 25 min of capsaicin application and before the first tDCS session (Day1-post-cap), and after the second tDCS session (Day2). RESULTS: Comparing Day2 to Day1-baseline measures, there was reduced corticomotor excitability (p < .05) and impaired CPM-effect (p < .05) after sham but not after active network-tDCS. Pain NRS ratings increased at Day2 compared to Day1-post-cap (p < .01) in both groups whereas no significant changes were found in pain sensitivity and TSP. CONCLUSIONS: Present findings demonstrate that tDCS applied over regions linked to the resting state motor network reverts the inhibition of corticomotor excitability and CPM impairment both provoked by prolonged experimental pain for 24 hr. SIGNIFICANCE: These findings highlight that the stimulation of the resting state motor network with multifocal tDCS may represent a potential cortical target to treat chronic pain, particularly in patients exhibiting maladaptive corticomotor excitability and impaired conditioned pain modulation effects.

Evidence for Enhanced Interoceptive Accuracy in Professional Musicians.

Interoception is defined as the perceptual activity involved in the processing of internal bodily signals. While the ability of internal perception is considered a relatively stable trait, recent data suggest that learning to integrate multisensory information can modulate it. Making music is a uniquely rich multisensory experience that has shown to alter motor, sensory, and multimodal representations in the brain of musicians. We hypothesize that musical training also heightens interoceptive accuracy comparable to other perceptual modalities. Thirteen professional singers, twelve string players, and thirteen matched non-musicians were examined using a well-established heartbeat discrimination paradigm complemented by self-reported dispositional traits. Results revealed that both groups of musicians displayed higher interoceptive accuracy than non-musicians, whereas no differences were found between singers and string-players. Regression analyses showed that accumulated musical practice explained about 49% variation in heartbeat perception accuracy in singers but not in string-players. Psychometric data yielded a number of psychologically plausible inter-correlations in musicians related to performance anxiety. However, dispositional traits were not a confounding factor on heartbeat discrimination accuracy. Together, these data provide first evidence indicating that professional musicians show enhanced interoceptive accuracy compared to non-musicians. We argue that musical training largely accounted for this effect.

Pain sensitivity and tactile spatial acuity are altered in healthy musicians as in chronic pain patients.

Extensive training of repetitive and highly skilled movements, as it occurs in professional classical musicians, may lead to changes in tactile sensitivity and corresponding cortical reorganization of somatosensory cortices. It is also known that professional musicians frequently experience musculoskeletal pain and pain-related symptoms during their careers. The present study aimed at understanding the complex interaction between chronic pain and music training with respect to somatosensory processing. For this purpose, tactile thresholds (mechanical detection, grating orientation, two-point discrimination) and subjective ratings to thermal and pressure pain stimuli were assessed in 17 professional musicians with chronic pain, 30 pain-free musicians, 20 non-musicians with chronic pain, and 18 pain-free non-musicians. We found that pain-free musicians displayed greater touch sensitivity (i.e., lower mechanical detection thresholds), lower tactile spatial acuity (i.e., higher grating orientation thresholds) and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. Moreover, we also found that musicians and non-musicians with chronic pain presented lower tactile spatial acuity and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. The significant increment of pain sensitivity together with decreased spatial discrimination in pain-free musicians and the similarity of results found in chronic pain patients, suggests that the extensive training of repetitive and highly skilled movements in classical musicians could be considered as a risk factor for developing chronic pain, probably due to use-dependent plastic changes elicited in somatosensory pathways.