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Available online on 15.07.2026 at http://jddtonline.info Journal of Drug Delivery and Therapeutics Open Access to Pharmaceutical and Medical Research Copyright © 2026 The Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited |
Open Access Full Text Article Case Series
Gut–Brain Axis Dysregulation in Migraine: Clinical Improvement Following Unani Management - A Case Series
Asia Khanam 1*, Rajesh 2 , Javed Ali Khan 3
1 Research Officer SL-I, Regional Research Centre (Unani), Prayagraj, Uttar Pradesh, under Central Council for Research in Unani Medicine, New Delhi, Ministry of AYUSH, Government of India, India.
² Research Officer SL-III, Regional Research Centre (Unani), Prayagraj, Uttar Pradesh, under Central Council for Research in Unani Medicine, New Delhi, Ministry of AYUSH, Government of India, India.
³ Research Associate, Regional Research Centre (Unani), Prayagraj, Uttar Pradesh, under Central Council for Research in Unani Medicine, New Delhi, Ministry of AYUSH, Government of India, India.
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Article Info: _______________________________________________ Article History: Received 17 April 2026 Reviewed 10 June 2026 Accepted 27 June 2026 Published 15 July 2026 _______________________________________________ Cite this article as: Khanam A, Rajesh, Khan JA, Gut–Brain Axis Dysregulation in Migraine: Clinical Improvement Following Unani Management - A Case Series, Journal of Drug Delivery and Therapeutics. 2026; 16(7):5-8 DOI: https://doi.org/10.22270/jddt.v16i7.7870 _______________________________________________ For Correspondence: Dr. Asia Khanam, Research Officer SL-I, Regional Research Centre (Unani), Prayagraj, Uttar Pradesh, under Central Council for Research in Unani Medicine, New Delhi, Ministry of AYUSH, Government of India, India |
Abstract _______________________________________________________________________________________________________________ Background: Migraine is a disabling neurological disorder frequently associated with gastrointestinal disturbances. Emerging evidence suggests an important role of the gut–brain axis in migraine pathophysiology. In Unani medicine, headache associated with gastrointestinal dysfunction is described as Sudaa-e-Shirki Maidi. Cases: Eight patients with migraine without aura associated with gastrointestinal disturbances attending the OPD of the Regional Research Centre (Unani), Prayagraj, were included. Common symptoms included recurrent headache, nausea, reflux, abdominal discomfort, constipation, and altered bowel habits. Intervention: Patients received Unani treatment comprising Itrifal Kishneezi and Khamira Gaozaban Sada for 12 weeks. Outcomes: The mean Visual Analog Scale (VAS) score decreased from 9.3 to 1.5, while the mean headache frequency reduced from 3.3 to 0.9 episodes per week. Complete symptomatic relief was observed in two patients, marked improvement in five patients, and moderate improvement in one patient. No adverse effects were reported. Conclusion: This case series suggests that Unani management may provide clinical benefit in migraine associated with gastrointestinal dysfunction and supports a possible role of gut–brain axis involvement in migraine pathophysiology. Keywords: Migraine; Gut–brain axis; Sudaa-e-Shirki Maidi; Gastrointestinal disturbances; Integrative Medicine; Case series |
Introduction:
Migraine is a common and disabling neurological disorder characterized by recurrent episodes of moderate to severe headache, often accompanied by nausea, photophobia, phonophobia, and dizziness. It affects approximately 14–15% of the global population and is a leading cause of disability worldwide. Increasing evidence suggests that migraine is a complex neurobiological disorder involving multiple mechanisms, including gut–brain axis dysregulation.1-3
Gastrointestinal disturbances such as nausea, reflux, abdominal discomfort, constipation, and altered bowel habits are frequently observed in migraine patients and may contribute to disease severity. Recent studies highlight a close interaction between gastrointestinal dysfunction and migraine through the gut–brain axis, suggesting that disturbances in gastrointestinal function may influence migraine expression and severity.3
In Unani medicine, headache associated with gastrointestinal dysfunction is described under Sudaa-e-Shirki Maidi, in which impaired digestion and the ascent of morbid vapors (bukharat) from the gastrointestinal tract are considered important pathogenic factors. The clinical features described in this condition show conceptual similarity with the contemporary understanding of the gut–brain axis.4,5 Therefore, the present case series was undertaken to evaluate the clinical response of Unani management in patients with migraine associated with gastrointestinal disturbances.
Cases Series:
This case series included eight patients with migraine without aura associated with gastrointestinal disturbances who attended the OPD of the Regional Research Centre (Unani), Prayagraj. Migraine was diagnosed clinically according to the International Classification of Headache Disorders, 3rd edition (ICHD-3). Patients commonly presented with recurrent headache accompanied by nausea, reflux, abdominal discomfort, constipation, and altered bowel habits. Based on clinical features and Unani diagnostic principles, the cases were classified as Sudaa-e-Shirki Maidi. Written informed consent was obtained from all patients for publication of anonymized clinical information.
All patients received Unani treatment comprising Itrifal Kishneezi and Khamira Gaozaban Sada for 12 weeks. Clinical assessment was performed using the Visual Analog Scale (VAS) for headache severity and frequency of headache episodes per week before and after treatment. Improvement in associated gastrointestinal symptoms was also recorded during follow-up. Patient characteristics and clinical outcomes are summarized in Tables 1 and 2.
Timeline and Follow-up:
Between March and July 2025, patients with migraine associated with gastrointestinal disturbances received Unani treatment at the Outpatient Department of the Regional Research Centre (Unani), Prayagraj, as part of routine clinical care. Patients were followed up weekly for 12 weeks to assess headache severity, frequency of headache episodes, associated gastrointestinal symptoms, treatment response, and adverse effects. Clinical improvement was observed in headache severity, headache frequency, and associated gastrointestinal symptoms.
|
Patient No. |
Age (years)/ Gender |
Temperament |
Duration of Illness (Years) |
Modern Diagnosis (ICHD-3) |
Unani Diagnosis |
Key Symptoms |
Associated G.I. Symptoms |
|
1 |
24/Female |
Bilious |
4 |
Migraine without aura |
Sudaa-e-Shirki Maidi |
Recurrent pulsating headache, dizziness |
Increased bowel frequency |
|
2 |
40/Male |
Phlegmatic |
2 |
Recurrent diffuse headache |
Constipation, abdominal bloating |
||
|
3 |
30/Female |
Bilious |
8 |
Headache and heaviness of head |
Acid regurgitation |
||
|
4 |
22/Female |
Phlegmatic |
6 |
Recurrent unilateral headache |
Heartburn, abdominal pain |
||
|
5 |
32/Female |
Bilious |
5 |
Recurrent throbbing headache |
Nausea, abdominal pain |
||
|
6 |
35/Male |
Bilious |
4 |
Recurrent pulsating headache |
Epigastric pain, heartburn |
||
|
7 |
38/Female |
Phlegmatic |
5 |
Headache and heaviness of head |
Heartburn, nausea |
||
|
8 |
20/Male |
Bilious |
2 |
Recurrent throbbing headache |
Epigastric pain, nausea |
|
Pt. S. No |
Treatment Given |
Duration (weeks) |
VAS Before |
VAS After |
Headache Frequency Before (per week) |
Headache Frequency After (per week) |
Outcome |
|
1 |
1. Itrifal Kishneezi 2. Khamira Gaozaban Sada |
12
|
9 |
0 |
3-4 |
0 |
Complete relief |
|
2 |
8 |
1 |
4-5 |
1 |
Marked improvement |
||
|
3 |
10 |
2 |
3-4 |
1 |
Marked improvement |
||
|
4 |
10 |
2 |
2-3 |
1 |
Marked improvement |
||
|
5 |
9 |
3 |
3-4 |
1 |
Marked improvement |
||
|
6 |
10 |
0 |
2-3 |
0 |
Complete relief |
||
|
7 |
8 |
3 |
3-4 |
2 |
Moderate improvement |
||
|
8 |
10 |
3 |
2-3 |
1 |
Marked improvement |
|
Parameter |
Before Treatment (Mean) |
After Treatment (Mean) |
|
VAS Score |
9.3 |
1.5 |
|
Frequency/week |
3.3 |
0.9 |
Therapeutic Actions of the Prescribed Formulations:6-8
Results:
Eight patients (five females and three males) with migraine without aura corresponding to the Unani entity Sudaa-e-Shirki Maidi were included in this case series. All patients completed the treatment and follow-up period, and no adverse effects were reported.
Clinical improvement was observed in headache severity, frequency of headache episodes, and associated gastrointestinal symptoms in all patients. The mean Visual Analog Scale (VAS) score decreased from 9.3 before treatment to 1.5 after treatment, while the mean frequency of headache episodes reduced from 3.3 to 0.9 episodes per week. Complete symptomatic relief was observed in two patients, marked improvement in five patients, and moderate improvement in one patient. Improvement in associated gastrointestinal symptoms, including nausea, reflux, abdominal discomfort, constipation, and altered bowel habits, was also observed during follow-up.
Discussion:
The findings of the present case series suggest a possible association between gastrointestinal dysfunction and migraine severity, consistent with both the contemporary understanding of the gut–brain axis and the Unani concept of Sudaa-e-Shirki Maidi. Improvement observed in headache severity, frequency of attacks, and associated gastrointestinal symptoms following Unani management indicates that correction of gastrointestinal dysfunction may contribute to clinical improvement in migraine.3,5-6,8
Recent studies suggest that gastrointestinal dysfunction may influence migraine through altered gut–brain signalling, neuroinflammatory pathways, and the release of neuropeptides such as calcitonin gene-related peptide (CGRP). The improvement observed in both migraine and gastrointestinal symptoms in the present cases is consistent with the growing evidence supporting gut–brain interactions in migraine.9,10
The therapeutic response may also be attributed to the traditional actions of the prescribed formulations. According to classical Unani literature, Itrifal Kishneezi is beneficial in headache associated with gastrointestinal disturbances, while Khamira Gaozaban Sada is regarded as a neurotonic formulation. The treatment protocol was based on the principles of correction of gastrointestinal dysfunction and restoration of humoral balance described in Unani medicine.5-6,7 The findings of the present case series are also consistent with previous reports describing improvement in migraine following Unani interventions.9
Limitations:
The present case series is limited by a small sample size, short follow-up duration, lack of standardized assessment tools for gastrointestinal symptoms, and absence of migraine-related quality of life assessment.
Patient Perspective:
Patients reported satisfaction with the treatment and noted significant improvement in headache severity, frequency of attacks, and associated gastrointestinal symptoms.
The present case series suggests that Unani management may provide clinical benefit in migraine associated with gastrointestinal dysfunction. Improvement observed in migraine severity and associated gastrointestinal manifestations supports the possible role of gut–brain axis involvement in migraine pathophysiology. Further controlled clinical studies are required to validate these findings.
Ethics approval and consent to participate: Not applicable
Consent for Publication: Written informed consent was obtained from all patients for publication of their anonymized clinical information.
Data Availability: The data supporting the findings of this study are available from the corresponding author upon reasonable request.
References:
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6. Anonymous. National Formulary of Unani Medicine, Part-I. New Delhi: Central Council for Research in Unani Medicine, Ministry of Health and Family Welfare, Government of India; 2006. p. 94, 110.
7. Khan AJ. Haziq. Karachi: Madina Publishing Company; 2019: p. 21.
8. Khan MA. Aksir-e-Azam. New Delhi: Idara Kitab-us-Shifa; 2011: p. 68.
9. Riyazuddin M, Shahid A, Siddiqui M. Effect of habb-e-quqaya in shaqeeqa (migraine without aura) - An open label clinical trial. J Ayurveda. 2021;15:147-152. https://doi.org/10.4103/joa.joa_311_20
10. Nguyen L, Hindiyeh N, Ray S, et al. The gut-brain connection and episodic migraine: an update. Curr Pain Headache Rep. 2023;27:765-774. https://doi.org/10.1007/s11916-023-01175-6 PMid:37792173 PMCid:PMC10713702