Pain Management

“Pain Management of Migraine Headache”

Dates of Project Initiation and Completion: [June 2015] – [June 2017]

Resulting Publications:

(1) Alireza Baratloo, Ahmed Negida, Gehad El Ashal, Nazanin Behnaz: Intravenous Caffeine for the Treatment of Acute Migraine: A Pilot Study. Journal of Caffeine Research; 05/2015; 5(3):125-129., DOI: 10.1089/jcr.2015.0004

(2) Alireza Baratloo, Sahar Mirbaha, Hossein Delavar Kasmaei, Pooya Payandemehr, Ahmed Elmaraezy, Ahmed Negida: Intravenous caffeine citrate vs. magnesium sulfate for reducing pain in patients with acute migraine headache; A prospective quasi-experimental study. The Korean journal of pain 07/2017; 30(3):176-182., DOI:10.3344/kjp.2017.30.3.176

(3) Hossein Delavar Kasmaei, Marzieh Amiri, Ahmed Negida, Samaneh Hajimollarabi, Nastaransadat Mahdavi: Ketorolac versus Magnesium Sulfate in Migraine Headache Pain Management; a Preliminary Study. 12/2016; in press(1)., DOI: 10.22037/emergency.v5i1.11257

(4) Amr Menshawy, Hussien Ahmed, Ammar Ismail, Abdelrahman Ibrahim Abushouk, Esraa Ghanem, Ravikishore Pallanti, Ahmed Negida: Intranasal sumatriptan for acute migraine attacks: a systematic review and meta-analysis. Neurological Sciences 09/2017; 39(1)., DOI: 10.1007/s10072-017-3119-y

(5) Baratloo, Alireza, Alaleh Rouhipour, Mohammad Mehdi Forouzanfar, Saeed Safari, Marzieh Amiri, and Ahmed Negida. “The role of caffeine in pain management: a brief literature review.” Anesthesiology and pain medicine 6, no. 3 (2016).

(6) Baratloo, Alireza, Marzieh Amiri, Mohammad Mehdi Forouzanfar, Sadegh Hasani, Samar Fouda, and Ahmad Negida. “Efficacy measurement of ketorolac in reducing the severity of headache.” Journal of Emergency Practice and Trauma 2, no. 1 (2016): 21-24.

Technical Summary of Work

Migraine is a common episodic disorder, the hallmark of which is a disabling headache generally associated with nausea, and/or light and sound sensitivity. The abortive (symptomatic) therapy of migraine ranges from the use of simple analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen to triptans, antiemetics, or the less commonly used dihydroergotamine. Abortive treatments are usually more effective if they are given early in the course of the headache; a large single dose tends to work better than repetitive small doses. Many oral agents are ineffective because of poor absorption secondary to migraine-induced gastric stasis.

Our research problem was that migraine patients do not respond optimally to these drugs. In addition, current migraine treatments are limited by the associated adverse events and the recurrence of migraine attacks. Our research focused on testing other potential drugs for the treatment of acute migraine headache.

We conducted clinical trials to test slow intravenous caffeine citrate infusion for the treatment of acute migraine attacks. Caffeine has a long profile of use as an adjuvant therapy for headache and migraine. The first study evaluated the safety and efficacy of intravenous caffeine citrate for patients with acute migraine headache. Sixty-one patients were enrolled who were diagnosed with migraine according to International Headache Society criteria. Patients received 60 mg caffeine citrate intravenously (i.v.) in about 10 min and Visual analog scale (VAS) pain scores were measured on baseline and 1 h and 2 h after caffeine infusion. We concluded that the infusion of 60 mg caffeine citrate i.v. is safe and well tolerated. It achieved therapeutic success for patients with acute migraine headache after 1 and 2 h. Further controlled studies are recommended.

In another study, we investigated the efficacy of intravenous caffeine citrate vs. magnesium sulfate for management of acute migraine headache. This was a prospective quasi-experimental study from January until May 2016 in two educational medical centers of Shahid Beheshti University of Medical Sciences (Shoahadaye Tajrish Hospital and Imam Hossein Hospital), Tehran, Iran. The study included patients who were referred to the emergency department and met the migraine diagnosis criteria of the International Headache Society. Patients were allocated into 2 groups receiving either 60 mg intravenous caffeine or 2 g intravenous magnesium sulfate. The pain scores, based on the visual analog scale, were recorded on admission, as well as one and two hours after receiving the drug. Our results showed that It is likely that both intravenous caffeine and intravenous magnesium sulfate can reduce the severity of migraine headache. Moreover, intravenous magnesium sulfate at a dose of 2 g might be superior to intravenous caffeine citrate 60 mg for the short-term management of migraine headache in emergency departments.

In the next study, we compared magnesium sulfate with ketorolac for acute migraine in a quasi-experimental clinical trial. 70 patients were treated with 30 mg ketorolac in one hospital and 1-gram magnesium sulfate in the other. We found that both ketorolac and magnesium sulfate are significantly effective in pain control of patients with migraine headache presenting to the emergency department. However, magnesium sulfate was superior to ketorolac both one and two hours after drug administration.

We also analyzed published clinical trial data to investigate evidence about the safety and efficacy of intranasal sumatriptan for the treatment of acute migraine at different doses and at different time points using data from published clinical trials. We found that intranasal sumatriptan is effective in the treatment of acute migraine.

Summary of the Significance of the Work

This project is important to my field because

Migraine is the 3rd most prevalent illness in the world. There is unmet clinical need to improve the treatment of migraine and develop novel treatment strategies to decrease the pain of acute migraine attack with less adverse events than the current conventional medications. Our research was helpful to advance the field by investigating potential agents for the management of acute migraine through a series of clinical trials.

Summary of the Implementation/Influence of the Work:

Our work was heavily cited by neuroscience research articles about migraine pain management which indicate that our work has an impact and significance.

[1] For example, the Linus Pauling Institute Micronutrient Information Center at Oregon State University provides scientific information on the health aspects of dietary factors and supplements, food, and beverages for the general public in the United States ( In their guide about the dietary information of Magnesium, under the section entitled “Migraine Headache”, they cited our clinical trial to highlight that magnesium sulfate infusion could be more effective and faster than other medications for acute migraine headache.

Source: (see reference no. 173).

[2] Overstreet and colleagues from the University of Alabama (USA) conducted a study to evaluate whether higher habitual dietary caffeine consumption was related to lower experimental pain sensitivity in a community-based sample. As a rational for their work, in the introduction, the authors wrote about the role of caffeine in pain management and they cited one of our articles as an evidence that acute administration of caffeine as a single bolus has therapeutic potential for acute pain management.


[3] Sahand Samieirad and colleagues evaluated the Caffeine versus codeine for pain and swelling management after implant surgeries. This work was based on our findings that Caffeine is effective in pain management. Therefore, the authors explored whether it can be effective for swelling management after implant surgeries.


[4] Lötsch and colleagues from Germany conducted an integrated Computational Analysis of Genes Associated with Human Hereditary Insensitivity to Pain. They analyzed data about the similarity between the biological processes associated with the genes causally involved in human insensitivity to pain and the biological processes in which the 413 drugs queried from the DrugBank database. Among these drugs, they found caffeine has a biological similarity that makes it involved in pain insensitivity. They cited our article as an evidence on the role of caffeine in pain management.