Brain activity changes after high/low frequency stimulation in a nonhuman primate model of central post-stroke pain

• Published in: Scientific reports 2024-07, Vol.14 (1), p.16527-11, Article 16527
• Main Authors: Nagasaka, Kazuaki, Higo, Noriyuki
• Format: Article
• Language: English
• Subjects: 631/378; 692/617; Allodynia; Analgesia; Analgesics; Animals; Brain - diagnostic imaging; Brain - physiopathology; Chronic pain; Chronic Pain - etiology; Chronic Pain - physiopathology; Chronic Pain - therapy; Cortex (motor); Disease Models, Animal; Functional magnetic resonance imaging; Humanities and Social Sciences; Hyperalgesia; Magnetic fields; Magnetic Resonance Imaging; Male; Motor Cortex - diagnostic imaging; Motor Cortex - physiopathology; multidisciplinary; Neuroimaging; Neuromodulation; Pain Management - methods; Pain perception; Pain Threshold; Science; Science (multidisciplinary); Signal processing; Somatosensory cortex; Somatosensory Cortex - diagnostic imaging; Somatosensory Cortex - physiopathology; Stroke; Stroke - complications; Stroke - physiopathology; Stroke - therapy; Thalamic pain; Transcranial magnetic stimulation; Transcranial Magnetic Stimulation - methods
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-67440-9

Central post-stroke pain (CPSP) is a chronic pain resulting from a lesion in somatosensory pathways. Neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) that target the primary motor cortex (M1), have shown promise for the treatment of CPSP. High-frequency (Hf) rTMS exhibits analgesic effects compared to low-frequency (Lf) rTMS; however, its analgesic mechanism is unknown. We aimed to elucidate the mechanism of rTMS-induced analgesia by evaluating alterations of tactile functional magnetic resonance imaging (fMRI) due to Hf- and Lf-rTMS in a CPSP monkey model. Consistent with the patient findings, the monkeys showed an increase in pain threshold after Hf-rTMS, which indicated an analgesic effect. However, no change after Lf-rTMS was observed. Compared to Lf-rTMS, Hf-rTMS produced enhanced tactile-evoked fMRI signals not only in M1 but also in somatosensory processing regions, such as the primary somatosensory and midcingulate cortices. However, the secondary somatosensory cortex (S2) was less active after Hf-rTMS than after Lf-rTMS, suggesting that activation of this region was involved in CPSP. Previous studies showed pharmacological inhibition of S2 reduces CPSP-related behaviors, and the present results emphasize the involvement of an S2 inhibitory system in rTMS-induced analgesia. Verification using the monkey model is important to elucidate the inhibition system.