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OMT Alleviated Migraine-Like Pain via Blockade of Trigeminal Activation

Journal: Journal of Osteopathic Medicine Date: 2023/12, 123(12):Pages: A27-A28. doi: Subito , type of study: animal experiment

Full text    (https://www.degruyter.com/document/doi/10.1515/jom-2023-2000/html)

Keywords:

animal experiment [36]
migraine [57]
OMT [2951]
osteopathic manipulative treatment [2973]
trigeminal activation [1]

Abstract:

Statement of Significance: Migraines represent one of the leading causes of disability worldwide(1). In the United States, 14.2% of adults report experiencing a migraine (2). While the pathophysiology of migraine pain is complex, sensitization of the trigeminovascular pathway is implicated(3). Osteopathic manipulative treatment (OMT) has been used clinically to supplement pharmacologic treatment affected patients, but wide-spread adoption of these treatments has been limited by a lack of mechanistic support. To determine if OMT is an effective method of treating the pain associated with an acute migraine, either prophylactically or abortively, and investigate its potential mechanisms of action. Research Methods: Female Sprague-Dawley rats were randomly divided into various treatment groups and assessed by behavioral testing (n = 8/group) and immunohistochemical (IHC) staining (n = 4 - 8/group). Migraines were induced by a two-hit method. The animals were primed with Complete Freund’s Adjuvant (CFA) diluted 1:1 with saline via injection to the upper trapezius muscles bilaterally (5 x 10 μL/side, total 100 μL). Six days later, they were exposed to umbellulone (50 mM in 5% DMSO/95% DiH2O, 50 μL), a known human migraine trigger (4), via inhalation for 30 minutes. The presence of cutaneous allodynia at the periorbital and hindpaw areas was determined every hour for 5 hours after umbellulone inhalation using calibrated von Frey filaments to elicit a withdrawal response. Subjects receiving OMT were given 2 minutes of therapy directed at the cervical soft tissues and spinal articulations for 1 min each either before inhalation of umbellulone (prophylactic) or after inhalation (abortive). For the IHC studies, subjects were sacrificed at 2 hours post-umbellulone treatment via transcardiac perfusion of fixatives, and brain tissue was collected and cryodissected for immunostaining. Because of their implication in migraine pain, the trigeminal nucleus caudalis (TNC) and the trigeminal ganglion (TG) were analyzed to determine the activation of the second-order sensory neurons by measuring expression of calcitonin gene-related peptide (CGRP), a pivotal neuropeptide implicated in migraine pathophysiology (5), and c-fos, an immediate early response gene (6). The number of c-fos or CGRP positive cells for each animal were counted at 6 (TNC) or 4 (TG) independent (non-adjacent) fields and the average number for each subject was reported. The experimenter was blinded for the treatment groups. Data Analysis: Our behavioral testing showed that umbellulone induced significant periorbital and hindpaw allodynia selectively in CFA-primed rats, which peaked at 2-3 hours post-umbellulone inhalation (P < 0.05 compared to baseline). OMT employed as an abortive measure, performed immediately after umbellulone administration, produced partial blockade of the development of cutaneous allodynia. For prophylactic treatment, OMT was performed three times at Days 1, 3, and 5 post-CFA. The multiple prophylactic episodes of OMT prevented the development of cutaneous allodynia associated with migraine-like pain induced by umbellulone. IHC analysis showed a significant increase of c-fos expression in TNC samples from subjects treated with CFA and umbellulone, which was blocked by prophylactic OMT. The number of c-fos positive cells at TNC was 492 ± 160 in the CFA + Umbellulone + OMT group, significantly lower than that of the CFA + Umbellulone + Sham group (1728 ± 249, P < 0.05). The expression of CGRP positive neurons in the TG samples increased significantly in subjects treated with CFA + umbellulone, which was normalized by prophylactic OMT (CFA+Umbellulone+OMT, 41±4 vs. CFA+Umbellulone+Sham, 111 ± 7, P<0.01). Conclusion: Two osteopathic techniques demonstrated effectiveness in blocking and mitigating migraine development as both a prophylactic and abortive treatment, likely by inhibiting trigeminal activation triggered by migraines in our rodent model. These findings provide mechanistic insights into the efficacy of OMT for migraines and support its potential as a non-pharmacological approach for migraine management. One limitation of our study is the use of only two osteopathic techniques to treat migraine-like pain. Future studies aim to assess other forms of OMT, including osteopathic cranial manipulative medicine, as well as treatment directed to other regions of the head and neck associated with the trigeminovascular pathway. Further studies on OMT can lend additional credibility for its use as an appropriate tool in clinical migraine management.


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