Disrupted Cortical Homeostatic Plasticity Due to Prolonged Capsaicin-induced Pain.

Homeostatic plasticity (HP) regulates cortical excitability (CE) stability but is disrupted in persistent pain conditions. This study investigated how prolonged experimental pain affects HP and if pain relief modulates disrupted HP. Twenty-four healthy participants were randomised into a PainRelief or NoPainRelief group and attended four sessions; two sessions on consecutive days, separated by two weeks. Transcranial magnetic stimulation motor-evoked potentials reflecting CE and quantitative sensory testing (QST) measures were recorded. A capsaicin (pain condition) or placebo (control condition) patch was applied to the hand. HP was induced by cathodal-cathodal transcranial direct current stimulation (HP1) with CE assessment before and after. The PainRelief group had ice applied to the patch, while the NoPainRelief group waited for five minutes; subsequently another HP induction (HP2) and CE assessment were performed. After 24 h with the patch on, HP induction (HP3), QST, and CE recordings were repeated. Capsaicin reduced CE and the pain condition showed disrupted homeostatic responses at all time points (HP1: showed CE inhibition instead of facilitation; HP2 & HP3: lack of CE facilitation). Conversely, homeostatic responses were induced at all time points for the placebo condition. Capsaicin pain disrupts HP which is not restored by ice-induced pain relief. Future research may explore the prevention of HP disruption by targeting capsaicin-induced nociception but not pain perception.

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.

Slowing in Peak-Alpha Frequency Recorded After Experimentally-Induced Muscle Pain is not Significantly Different Between High and Low Pain-Sensitive Subjects.

Peak alpha frequency (PAF) reduces during cutaneous pain, but no studies have investigated PAF during movement-related muscle pain. Whether high-pain sensitive (HPS) individuals exhibit a more pronounced PAF response to pain than low-pain sensitive (LPS) individuals is unclear. As a pain model, twenty-four participants received nerve growth factor injections into a wrist extensor muscle at Day 0, Day 2, and Day 4. At Day 4, a subgroup of twelve participants also undertook eccentric wrist exercise to induce additional pain. Pain numerical rating scale (NRS) scores and electroencephalography were recorded at Day 0 (before injection), Day 4, and Day 6 for 3 minutes (eyes closed) with wrist at rest (Resting-state) and extension (Contraction-state). The average pain NRS scores in contraction-state across Days were used to divide participants into HPS (NRS-scores≥2) and LPS groups. PAF was calculated by frequency decomposition of electroencephalographic recordings. Compared with Day 0, contraction NRS-scores only increased in HPS-group at Day 4 and Day 6 (P < .001). PAF in Contraction-state decreased in both groups at Day 6 compared with Day 0 (P = .011). Across days, HPS-group showed faster PAF than LPS-group during Resting-state and Contraction-state (P < .04). Average pain NRS-scores across days during Contraction-states correlated with PAF at Day 0 (P = .012). Pain NRS-scores were associated with PAF during Contraction-state at Day 4 and Day 6 (P < .05). PERSPECTIVE: PAF was slowed during long-lasting movement-related pain in both groups, suggesting a widespread change in cortical excitability independent of the pain sensitivity. Moreover, HPS individuals showed faster PAF than LPS individuals during muscle pain, which may reflect a different cognitive, emotional, or attentional response to muscle pain among individuals.

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.