Medication overuse headache (MOH) is an iatrogenic condition that promotes the transformation of episodic migraine into a chronic disorder, and is associated with disability and dysfunction of endogenous pain modulatory mechanisms. Repetitive transcranial magnetic stimulation (rTMS) at high frequency is a non invasive neuromodulatory approach with putative analgesic effects and the capability to influence descending pain control circuits; however, its specific efficacy in MOH and its impact on temporal modulation phenomena such as Offset Analgesia (OA) remain not completely defined. The primary aim of this thesis is to evaluate the clinical efficacy of high frequency rTMS as an adjunctive treatment in patients with MOH undergoing a detoxification program, by measuring reduction in monthly headache days and the potential restoration or enhancement of Offset Analgesia (OA) as an index of recovery of descending pain modulation. The protocol consisted of a controlled three arm study (rTMS targeted to the facial representation of M1, rTMS targeted to the upper limb representation of M1, and sham stimulation). 60 patients with MOH admitted for detoxification were enrolled. Assessments were performed at baseline, after five rTMS sessions (T1), at 1 month (T2) and at 3 months (T3, ongoing), and included clinical questionnaires (MIDAS, HIT 6, MSQ, HADS, LDQ, SDS, ASC 12, PGIC), headache diaries, quantitative sensory testing (WDT, CDT, HPT) and thermal protocols for OA/CT (constant trial) applied to trigeminal and forearm regions. Results indicate a somatotopic effect of rTMS on endogenous pain modulation: stimulation targeted to the facial representation of M1 was able to restore trigeminal OA in patients with MOH, suggesting selective recovery of descending modulatory circuits. Although short term additional clinical benefits of active rTMS did not clearly exceed those of sham stimulation, the observed neurophysiological modulation supports the use of rTMS as a complementary therapeutic strategy and warrants longitudinal studies with extended follow up and optimized stimulation protocols.
La cefalea da abuso di farmaci (Medication Overuse Headache, MOH) è una condizione iatrogena che favorisce la trasformazione dell’emicrania episodica in una forma cronica, associata a disabilità e alterazioni dei meccanismi endogeni di modulazione del dolore. La stimolazione magnetica transcranica ripetitiva ad alta frequenza (rTMS) è una strategia neuromodulatoria non invasiva con potenziale effetto antalgico e modulatore sui circuiti discendenti del dolore, ma la sua efficacia specifica in MOH e il suo impatto su fenomeni di modulazione temporale come l’Offset Analgesia (OA) restano poco definiti. Obiettivo principale di questa tesi è quello di valutare l’efficacia clinica di rTMS ad alta frequenza come trattamento aggiuntivo in pazienti con MOH sottoposti a programma di disintossicazione, misurando la riduzione dei giorni di cefalea mensili e l’eventuale ripristino o potenziamento del fenomeno di Offset Analgesia come indice di recupero della modulazione discendente del dolore. Il protocollo prevede uno studio controllato con tre bracci (rTMS su area M1 rappresentazione facciale, rTMS su M1 rappresentazione arto superiore, sham). Sono stati valutati 60 pazienti con MOH ricoverati per disintossicazione. Valutazioni a baseline, dopo 5 sedute di rTMS (T1), a 1 mese (T2) e a 3 mesi (T3, in corso): questionari clinici (MIDAS, HIT 6, MSQ, HADS, LDQ, SDS, ASC 12, PGIC), diario cefalea, QST (WDT, CDT, HPT) e protocolli termici per OA/CT (constant trial) su regione trigeminale e avambraccio. I dati ottenuti suggeriscono un effetto somatotopico della rTMS sulla modulazione endogena del dolore: la stimolazione mirata alla rappresentazione facciale di M1 può ripristinare l’OA trigeminale nei pazienti con MOH, indicando un recupero selettivo dei circuiti discendenti. Sebbene i benefici clinici aggiuntivi a breve termine non siano risultati nettamente superiori allo sham, la modulazione neurofisiologica osservata supporta l’impiego di rTMS come trattamento complementare e giustifica studi longitudinali con follow up esteso e protocolli ottimizzati.
Effetti della stimolazione magnetica transcranica ripetitiva (rTMS) ad alta frequenza sui meccanismi di controllo endogeno del dolore nei pazienti con cefalea da abuso da farmaci (MOH).
CAVIGIOLI, CAMILLA
2024/2025
Abstract
Medication overuse headache (MOH) is an iatrogenic condition that promotes the transformation of episodic migraine into a chronic disorder, and is associated with disability and dysfunction of endogenous pain modulatory mechanisms. Repetitive transcranial magnetic stimulation (rTMS) at high frequency is a non invasive neuromodulatory approach with putative analgesic effects and the capability to influence descending pain control circuits; however, its specific efficacy in MOH and its impact on temporal modulation phenomena such as Offset Analgesia (OA) remain not completely defined. The primary aim of this thesis is to evaluate the clinical efficacy of high frequency rTMS as an adjunctive treatment in patients with MOH undergoing a detoxification program, by measuring reduction in monthly headache days and the potential restoration or enhancement of Offset Analgesia (OA) as an index of recovery of descending pain modulation. The protocol consisted of a controlled three arm study (rTMS targeted to the facial representation of M1, rTMS targeted to the upper limb representation of M1, and sham stimulation). 60 patients with MOH admitted for detoxification were enrolled. Assessments were performed at baseline, after five rTMS sessions (T1), at 1 month (T2) and at 3 months (T3, ongoing), and included clinical questionnaires (MIDAS, HIT 6, MSQ, HADS, LDQ, SDS, ASC 12, PGIC), headache diaries, quantitative sensory testing (WDT, CDT, HPT) and thermal protocols for OA/CT (constant trial) applied to trigeminal and forearm regions. Results indicate a somatotopic effect of rTMS on endogenous pain modulation: stimulation targeted to the facial representation of M1 was able to restore trigeminal OA in patients with MOH, suggesting selective recovery of descending modulatory circuits. Although short term additional clinical benefits of active rTMS did not clearly exceed those of sham stimulation, the observed neurophysiological modulation supports the use of rTMS as a complementary therapeutic strategy and warrants longitudinal studies with extended follow up and optimized stimulation protocols.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14239/33045