Quantitative Proteomic Analysis Reveals apoE4-Dependent Phosphorylation of the Actin-Regulating Protein VASP.

Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease. While neurons generally produce a minority of the apoE in the central nervous system, neuronal expression of apoE increases dramatically in response to stress and is sufficient to drive pathology. Currently, the molecular mechanisms of how apoE4 expression may regulate pathology are not fully understood. Here, we expand upon our previous studies measuring the impact of apoE4 on protein abundance to include the analysis of protein phosphorylation and ubiquitylation signaling in isogenic Neuro-2a cells expressing apoE3 or apoE4. ApoE4 expression resulted in a dramatic increase in vasodilator-stimulated phosphoprotein (VASP) S235 phosphorylation in a protein kinase A (PKA)-dependent manner. This phosphorylation disrupted VASP interactions with numerous actin cytoskeletal and microtubular proteins. Reduction of VASP S235 phosphorylation via PKA inhibition resulted in a significant increase in filopodia formation and neurite outgrowth in apoE4-expressing cells, exceeding levels observed in apoE3-expressing cells. Our results highlight the pronounced and diverse impact of apoE4 on multiple modes of protein regulation and identify protein targets to restore apoE4-related cytoskeletal defects.

Comparison of intradermal mesotherapy with systemic therapy in the treatment of low back pain: A prospective randomized study.

INTRODUCTION: Musculoskeletal pain such as low back pain (LBP) are routinely encountered in the ED and contribute to ED overcrowding. The aim of our study was to compare the efficiency of mesotherapy with systemic therapy in pain control in patients with lumbar disk herniation. METHODS: We conducted this prospective parallel randomized controlled trial with the patients admitted to the emergency department with low back pain related to herniated lumbar disk. Mesotherapy was performed to one group, while intravenous dexketoprofen was administered to the control group. Changes in pain intensity at 15th minute, 30th minute, 60th minute and 24th hours after treatment using Visual Analogue Scale (VAS), need to use analgesic drug within 24 h after treatment, and adverse effect of the treatment methods were compared between groups. RESULTS: The decreases in pain intensity were statistically significantly higher in mesotherapy group for all time intervals. The need to use analgesics was statistically significantly three fold higher in the systemic therapy group. There was no statistically significant difference in having any adverse effect between study groups during one-week follow-up period. CONCLUSIONS: Changes in medical practices, from the systemic administration of NSAIDs to the minimally invasive techniques such as mesotherapy with potent efficacy and minimal side effects, may enhance the ability of EDs to meet the waiting time targets and improve patient's satisfaction.

Intradermal injection for hiccup therapy in the Emergency Department.

Hiccup is a condition caused by involuntary contraction of inspiratory muscles, especially the diaphragm. Although it is generally considered as a physiological. response, if hiccup persists for a long time, it can lead to many undesirable conditions such as depression, weight loss, insomnia, and fatigue. A 35-year-old male patient was admitted to our emergency department with hiccup lasting for 15 h. He had a history of several hiccup attacks. Classical non-pharmacological and pharmacological therapies were used to treat the condition without any response. As an alternative method, an intradermal injection was applied. A mixture of thiocolchicoside and lidocaine was administered intradermally to a depth of 1-3 mm at the epigastric region and adjacent to the sternocleidomastoid muscle. The patient's hiccup ended after the intradermal injection procedure. During 48 h of follow-up the hiccup attack did not develop again. No complications related to the process were detected. This is the first case in the literature demonstrating the use of intradermal injection to terminate hiccups. The intradermal injection approach can be administered in cases of hiccups that do not respond to medical treatment.

Comparison of effectiveness coolant spray and placebo in patients with acute ankle trauma prospective randomized controlled trial.

INTRODUCTION: Coolant spray application in musculoskeletal injuries is an effective and harmless method to treat pain and reduce functional limitation. This study assessed the clinical value of coolant spray application on patient comfort before and during the radiographic imaging process along with its early analgesic and anti-edema effects. METHODS: A total of 155 patients, admitted to the emergency department between April 1, 2019, and June 31, 2019, were included in this study. The patients were randomly assigned to either a coolant spray or a saline spray (placebo) group. To the coolant spray group patients, Cryos ®Spray (Phyto Performance, Italy) was applied. To the placebo group patients, a normal saline solution in a bottle covered with white opaque paper and refrigerated at 4 °C was sprayed. Radiographic images of the patients were scored for appropriateness of the standard imaging characteristics. RESULTS: The mean scores were 8.13 ± 1.8 and 6.58 ± 2.2 for the coolant spray and normal saline spray groups, respectively; the differences were statistically significant between the two groups (mean difference: -1.56, 95% CI:-2.20 to -0.92; p = .000). Patients with fractures on their radiographs and treated with coolant spray received higher scores than similar patients treated with normal saline spray (mean difference:-1.92, 95% CI:-3.28 to -0.55; p = .009). The proportion of patients requesting analgesic treatment before discharge was statistically lower in the coolant spray group compared to the normal saline group (p = .025). CONCLUSIONS: The radiographic images taken after coolant spray intervention in patients with acute ankle trauma were more successful in showing the target structures.

Comparison of ibuprofen and piroxicam gel in the treatment of trauma pain: A randomized double-blind trial of geriatric population.

OBJECTIVE: This study aimed to compare the analgesic efficacy of topical ibuprofen and topical piroxicam for acute musculoskeletal injuries. METHODS: In this prospective, randomized, controlled, double-blinded study, geriatric patients were assigned to groups to receive either topical ibuprofen (n = 70) or topical piroxicam (n = 69). The first dose of gel was applied in the emergency department and the remaining doses were self-administered at home by the patients thrice daily for 72 h. For each patient, the initial baseline visual analog scale (VAS) score (V 0) was compared with the VAS scores at the 60 min (V1), 120 min (V2), 24 h (V3) and 72 h (V4) time points. The decreases in VAS scores, clinical effectiveness of the treatments, and incidence of adverse events were evaluated. RESULTS: In the topical ibuprofen group, the VAS scores were significantly lower at each measurement time point compared to baseline (p < .001). The results were as follows: V0 -V: 1.08, 95% CI: 0.56-1.61; V0 -V2: 1.09, 95% CI: 0.49-1.69; V0 -V3: 1.44, 95% CI: 0.81-2.07; V0 -V4: 1.59, 95% CI: 0.91-2.26. The mean percentage decrease in the VAS scores in the topical ibuprofen group was significantly higher than that in the topical piroxicam group (p < .001). The clinical effect of treatment was found to be significantly higher for the ibuprofen gel group (p < .001). There was no substantial difference in treatment-related adverse events between the groups (p > .05). CONCLUSION: Ibuprofen gel, which is a safe treatment option for geriatric patients, is more clinically effective than piroxicam gel. Response to Reviewers.

Comparison of topical capsaicin and topical piroxicam in the treatment of acute trauma-induced pain: A randomized double-blind trial.

BACKGROUND: This study aimed to compare the analgesic efficacy of topical capsaicin and topical piroxicam in acute musculoskeletal injuries. METHODS: This is a prospective, randomized, controlled, double-blinded study. The data for the 67 patients in the piroxicam group and the 69 in the capsaicin group were examined. The initial visual analog scale (VAS) scores were compared with the 60th and 120th minute as well as the 24th and 72nd hour values. Differences between the VAS scores, clinical effectiveness of the treatment and side effects were evaluated. RESULTS: In the capsaicin group, the mean difference in the delta VAS scores was significantly higher at each measurement time. The mean of the percentage of reduction in the VAS scores of the topical capsaicin group was significantly higher than that in the topical piroxicam group. The highest difference in terms of both outcomes was determined at the 72nd hour VAS change. Mean differences were 1.53 (95% CI: 0.85-2.221) and 19.7 (95% CI: 12.4-27.2) respectively (p < 0.001). In the capsaicin group, the clinical effect of the treatment was found significantly higher (p < 0.01). The difference between the clinical effectiveness of the groups regarding the treatment outcomes was also statistically significant (p < 0.001). There was no significant difference between the patient groups regarding the presence of side effects. CONCLUSION: Topical capsaicin can be used as an alternative to topical piroxicam initially and at follow-up in patients presenting to the emergency department with acute pain as there were no observable differences in side-effects between the two groups.

Comparison of two scores of short term serious outcome in COPD patients.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) related visits to the emergency department have increased substantially during the past decade. An important challenge facing emergency physicians when treating COPD patients is deciding on disposition. The aim of this study was to evaluate Integrated Pulmonary Index scoring to guide the disposition decisions of emergency physicians by comparing its compatibility with Ottawa COPD Risk Score. METHODS: This is a prospective methodological study, in which we compared the accuracies of the Integrated Pulmonary Index and Ottawa COPD Risk Score in predicting of the short-term serious outcomes in patients admitted to the emergency department with COPD exacerbation. Patients who admitted to our emergency department between 01.01.2019-31.03.2019 were evaluated. THE RESULTS: Among the 208 patients, there were 154 (74.0%) short-term serious outcomes. The AUCs were 0.915 and 0.943 for Integrated Pulmonary Index and Ottawa COPD Risk Score, respectively. The difference between AUCs for two scores was not statistically significant. The best cut-off point for Integrated Pulmonary Index and Ottawa COPD Risk Score were ≤3 and >4, respectively. For these best cut-off points, the sensitivity and specificity of Integrated Pulmonary Index were 92.9 and 87.1, respectively. The sensitivity and specificity of Ottawa COPD Risk Score were 99.3 and 85.2, respectively. Besides, the accuracy of Integrated Pulmonary Index was 91.3, and the accuracy of Ottawa COPD Risk Score was 95.7. CONCLUSIONS: Integrated Pulmonary Index was a potential candidate for evaluating respiratory status and prediction of short-term severe events in patients with acute COPD exacerbation in emergency departments.

Differential retrotranslocation of mitochondrial Bax and Bak.

The Bcl-2 proteins Bax and Bak can permeabilize the outer mitochondrial membrane and commit cells to apoptosis. Pro-survival Bcl-2 proteins control Bax by constant retrotranslocation into the cytosol of healthy cells. The stabilization of cytosolic Bax raises the question whether the functionally redundant but largely mitochondrial Bak shares this level of regulation. Here we report that Bak is retrotranslocated from the mitochondria by pro-survival Bcl-2 proteins. Bak is present in the cytosol of human cells and tissues, but low shuttling rates cause predominant mitochondrial Bak localization. Interchanging the membrane anchors of Bax and Bak reverses their subcellular localization compared to the wild-type proteins. Strikingly, the reduction of Bax shuttling to the level of Bak retrotranslocation results in full Bax toxicity even in absence of apoptosis induction. Thus, fast Bax retrotranslocation is required to protect cells from commitment to programmed death.

Parkin promotes proteasomal degradation of misregulated BAX.

The pro-apoptotic BCL-2 protein BAX commits human cells to apoptosis by permeabilizing the outer mitochondrial membrane. BAX activation has been suggested to require the separation of helix α5 from α6 - the 'latch' from the 'core' domain - among other conformational changes. Here, we show that conformational changes in this region impair BAX translocation to the mitochondria and retrotranslocation back into the cytosol, and therefore BAX inhibition, but not activation. Redirecting misregulated BAX to the mitochondria revealed an alternative mechanism of BAX inhibition. The E3 ligase parkin, which is known to trigger mitochondria-specific autophagy, ubiquitylates BAX K128 and targets the pro-apoptotic BCL-2 protein for proteasomal degradation. Retrotranslocation-deficient BAX is completely degraded in a parkin-dependent manner. Although only a minor pool of endogenous BAX escapes retrotranslocation into the cytosol, parkin-dependent targeting of misregulated BAX on the mitochondria provides substantial protection against BAX apoptotic activity.

Prognostic value of blood gas parameters and end-tidal carbon dioxide values in out-of-hospital cardiopulmonary arrest patients

Background/aim: This study aimed to evaluate the usefulness of blood gas and end-tidal carbon dioxide (EtCO2) measurements for predicting return of spontaneous circulation (ROSC) and for evaluating post-ROSC neurological survival. Materials and methods: This was a prospective case control study utilizing Atatürk University's database of adult nontraumatic patients (over 18 years old) with out-of-hospital cardiac arrest (OHCA) over the course of a year. The neurological status of the patients was evaluated after 1 h at ROSC and at hospital discharge, as defined by the cerebral performance category score. The blood gas parameters pH, PO2, PCO2, lactate, and BE were compared with EtCO2 from capnography and arteriol/alveolar carbon dioxide difference (AaDCO2) by using both blood gas and capnography upon admission to the emergency department and at ROSC. Results: A total of 155 patients were included in the study to form the control group with ROSC. The PO2, PCO2, and AaDCO2 values showed a prognostic marker for the supply of ROSC (P < 0.05). The EtCO2,lactate, and BE values measured by the blood gas were found to be insignificant in the prediction of ROSC (P > 0.05). Conversely, AaDCO2 was found to be significant in ROSC estimation (P < 0.05), but not in neurological evaluation (P > 0.05). Conclusion: Blood gas parameters and EtCO2 are sufficient in predicting ROSC. The value of AaDCO2 calculated using EtCO2 and PO2may be used in predicting the prognosis of OHCA patients, but this value does not provide any conclusions concerning neurological survival.

Autologous rabbit adipose tissue-derived mesenchymal stromal cells for the treatment of bone injuries with distraction osteogenesis.

BACKGROUND AIMS: Adipose tissue-derived mesenchymal stromal cells (MSCs) have a higher capacity for proliferation and differentiation compared with other cell lineages. Although distraction osteogenesis is the most important therapy for treating bone defects, this treatment is restricted in many situations. The aim of this study was to examine the therapeutic potential of adipose tissue-derived MSCs and osteoblasts differentiated from adipose tissue-derived MSCs in the treatment of bone defects. METHODS: Bone defects were produced in the tibias of New Zealand rabbits that had previously undergone adipose tissue extraction. Tibial osteotomy was performed, and a distractor was placed on the right leg of the rabbits. The rabbits were placed in control (group I), stem cell (group II) and osteoblast-differentiated stem cell (group III) treatment groups. The rabbits were sacrificed, and the defect area was evaluated by radiologic, biomechanical and histopathologic tests to examine the therapeutic effects of adipose tissue-derived MSCs. RESULTS: Radiologic analyses revealed that callus density and the ossification rate increased in group III compared with group I and group II. In biomechanical tests, the highest ossification rate was observed in group III. Histopathologic studies showed that the quality of newly formed bone and the number of cells active in bone formation were significantly higher in group III rabbits compared with group I and group II rabbits. CONCLUSIONS: These data reveal that osteoblasts differentiated from adipose tissue-derived MSCs shorten the consolidation period of distraction osteogenesis. Stem cells could be used as an effective treatment for bone defects.

Effect of coolant spray on rib fracture pain of geriatric blunt thoracic trauma patients: a randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the effectiveness of cryotherapy in elderly patients with rib fractures due to blunt thoracic trauma. METHODS: In this prospective randomized controlled study, geriatric patients were assigned to groups to receive either coolant spray (n=51) or placebo spray (n=50). The visual analog scale scores of all patients were recorded before starting spray application (V0), as well as at 10th (V1), 20th (V2), 30th (V3), 60th (V4), 120th (V5), and 360th (V6) minute. The mean decreases in the visual analog scale scores were calculated. RESULTS: The differences between V0 and V1, V0 and V2, V0 and V3, and V0 and V4 mean visual analog scale scores measured in the coolant spray group were found to be significantly higher (p<0.001). In V1, V2, V3, and V4 measurements, the incidence of "clinical effectiveness" in the coolant spray group was significantly higher than in the placebo group (p=0.001). CONCLUSIONS: Coolant spray therapy can be used as a component of multimodal therapy to provide adequate analgesia due to rib fractures in geriatric patients.

Lysosomal proteomics reveals mechanisms of neuronal apoE4associated lysosomal dysfunction.

ApoE4 is the primary risk factor for Alzheimer's Disease. While apoE is primarily expressed by astrocytes, AD pathology including endosomal abnormalities and mitochondrial dysfunction first occurs in neurons. Lysosomes are poised at the convergence point between these features. We find that apoE4-expressing cells exhibit lysosomal alkalinization, reduced lysosomal proteolysis, and impaired mitophagy. To identify driving factors for this lysosomal dysfunction, we performed quantitative lysosomal proteome profiling. This revealed that apoE4 expression results in lysosomal depletion of Lgals3bp and accumulation of Tmed5 in both Neuro-2a cells and postmitotic human neurons. Modulating the expression of both proteins affected lysosomal function, with Tmed5 knockdown rescuing lysosomal alkalinization in apoE4 cells, and Lgals3bp knockdown causing lysosomal alkalinization and reduced lysosomal density in apoE3 cells. Taken together, our work reveals that apoE4 exerts gain-of-toxicity by alkalinizing the lysosomal lumen, pinpointing lysosomal Tmed5 accumulation and Lgals3bp depletion as apoE4-associated drivers for this phenotype.

A fatal folk remedy: rope wrapping to the back.

BACKGROUND: Despite the developments in medicine in recent years, people in many regions of the world still tend to use alternative, or non-medical, folkloric treatment methods for many different health problems. One of these methods is "rope wrapping to the back," which is considered to be therapeutic for patients with lumbar disc hernias or low back pain. This method is practiced by local individuals without medical training. CASE REPORT: Over the course of 3 years, 14 patients, 8 women and 6 men, presented to Atatürk University and Erzurum state hospitals in eastern Turkey after undergoing the folk treatment known as "rope wrapping to the back" for low back pain. One of the patients, who had symptoms of systemic infection, later died. Of the other patients, 4 had local infections, 6 had unresolved complaints, and 3 had other complaints. Nine of the patients were treated in the emergency department and 4 required surgery. Two case reports are provided as examples. CONCLUSION: Improvements are needed to increase the accessibility of health care, improve physician-patient communication, and provide information to people, so as to prevent the use of folk remedies, which can have serious complications, sometimes resulting in death.

A Selective Histamine H4 Receptor Antagonist, JNJ7777120, Role on glutamate Transporter Activity in Chronic Depression.

Glutamate release and reuptake play a key role in the pathophysiology of depression. glutamatergic nerves in the hippocampus region are modulated by histaminergic afferents. Excessive accumulation of glutamate in the synaptic area causes degeneration of neuron cells. The H4 receptor is defined as the main immune system histamine receptor with a pro-inflammatory role. To understand the role of this receptor, the drug JNJ7777120 was used to reveal the chronic depression-glutamate relationship. We have important findings showing that the H4 antagonist increases the glutamate transporters' instantaneous activity. In our experiment, it has been shown that blocking the H4 receptor leads to increased neuron cell viability and improvement in behavioral ability due to glutamate. Therefore, JNJ can be used to prevent neurotoxicity, inhibit membrane phospholipase activation and free radical formation, and minimize membrane disruption. In line with our findings, results have been obtained that indicate that JNJ will contribute to the effective prevention and treatment of depression.

Coordinated Transcriptional and Catabolic Programs Support Iron-Dependent Adaptation to RAS-MAPK Pathway Inhibition in Pancreatic Cancer.

The mechanisms underlying metabolic adaptation of pancreatic ductal adenocarcinoma (PDA) cells to pharmacologic inhibition of RAS-MAPK signaling are largely unknown. Using transcriptome and chromatin immunoprecipitation profiling of PDA cells treated with the MEK inhibitor (MEKi) trametinib, we identify transcriptional antagonism between c-MYC and the master transcription factors for lysosome gene expression, the MiT/TFE proteins. Under baseline conditions, c-MYC and MiT/TFE factors compete for binding to lysosome gene promoters to fine-tune gene expression. Treatment of PDA cells or patient organoids with MEKi leads to c-MYC downregulation and increased MiT/TFE-dependent lysosome biogenesis. Quantitative proteomics of immunopurified lysosomes uncovered reliance on ferritinophagy, the selective degradation of the iron storage complex ferritin, in MEKi-treated cells. Ferritinophagy promotes mitochondrial iron-sulfur cluster protein synthesis and enhanced mitochondrial respiration. Accordingly, suppressing iron utilization sensitizes PDA cells to MEKi, highlighting a critical and targetable reliance on lysosome-dependent iron supply during adaptation to KRAS-MAPK inhibition. SIGNIFICANCE: Reduced c-MYC levels following MAPK pathway suppression facilitate the upregulation of autophagy and lysosome biogenesis. Increased autophagy-lysosome activity is required for increased ferritinophagy-mediated iron supply, which supports mitochondrial respiration under therapy stress. Disruption of ferritinophagy synergizes with KRAS-MAPK inhibition and blocks PDA growth, thus highlighting a key targetable metabolic dependency. See related commentary by Jain and Amaravadi, p. 2023. See related article by Santana-Codina et al., p. 2180. This article is highlighted in the In This Issue feature, p. 2007.

Acute abdomen associated with organophosphate poisoning.

BACKGROUND: Pesticides are extensively used in developed and developing countries. OBJECTIVES: The present study was designed to evaluate the clinical course of patients with carbamate or organophosphate poisoning presenting to a University-based emergency department (ED). METHODS: All consecutive patients admitted to our ED due to intoxication with carbamate or organophosphate compounds over a 2-year period were enrolled prospectively. RESULTS: A total of 49 consecutive patients (26 females) were diagnosed with carbamate or organophosphate poisoning in the 24-month study period. The mean age of the patients was 32±13.1 years (range 16-70 years). Signs and symptoms most frequently noted in patients with organophosphate or carbamate poisoning were perspiration, vomiting, and bronchorrhea. Abdominal pain was reported by 65.3% of the patients. Abdominal ultrasonography was performed in 22 patients who complained of abdominal pain as a leading symptom. Among these, 63.6% were found to have abdominal free fluid. Pancreatitis and peritonitis developed in one case. Atropine treatment was administered for approximately 24-36h, with a mean total dose of 13.75±6.75mg. Pralidoxime was administered to 70.9% of patients with organophosphate poisoning, but was not used in patients intoxicated with carbamates. Endotracheal intubation and mechanical ventilatory support were required in 14.2% of the patients. Mean duration of mechanical ventilation was 3.7±2.2 days. The overall mortality rate was 10.2%. CONCLUSION: Patients with a diagnosis of organophosphate poisoning should be screened for acute abdomen. The findings in our study suggest that these patients should undergo routine abdominal ultrasonography, especially in cases with abdominal pain along with other abdominal complaints.

Electromyographic and electroneurographic changes in internal nasal muscles after endonasal and external rhinoplasty.

BACKGROUND: Anatomical structures of the nose (including muscles) are elevated, sutured, or reshaped during rhinoplasty. Electromyography and electroneurography are the objective electrophysiologic tests performed for the direct measurement of nasal muscle function. OBJECTIVES: The authors investigate the predictive values and functional status of nasal muscles during voluntary facial and nasal movements following open and closed rhinoplasty. METHODS: In 48 patients who underwent rhinoplasty, surface electrodes were placed to preoperatively and postoperatively measure nasal muscle function with electromyography and electroneurography. Results were analyzed according to whether the patient had undergone open or closed rhinoplasty. RESULTS: Electroneurography amplitudes were decreased postoperatively on both sides, in both groups. This increase was statistically significant (p < .001). Electromyography-recorded amplitude of nasal muscle contraction tension significantly decreased postoperatively in response to all voluntary movements in two cases in the closed rhinoplasty group (6.6%) and in two cases in the open rhinoplasty group (11.1%). In essence, the activity strength of the nasal muscles decreased postoperatively for some patients. The mean differences between the two groups were not statistically significant (p = .280). CONCLUSIONS: The data showed no meaningful difference in injury to the nasal muscular layer between open and closed rhinoplasty.

Intradermal mesotherapy versus intravenous dexketoprofen for the treatment of migraine headache without aura: a randomized controlled trial.

BACKGROUND: Migraine is a prevalent disabling primary headache disorder that is classified into two major types: migraine without aura and migraine with aura. New therapeutic methods to reduce migraine headaches in the emergency department (ED) include intradermal mesotherapy. OBJECTIVE: Compare the efficacy of intradermal mesotherapy versus a systemic therapy in pain control in patients with headache related to migraine without aura. DESIGN: Prospective parallel-group randomized controlled trial. SETTING: University hospital in Turkey. PATIENTS AND METHODS: Patients 18 years of age and older who were admitted to the ED over a 15-month period with headache related to migraine without aura were eligible for inclusion if they had a VAS score of 4 or above. Patients were randomly allocated to one session of mesotherapy or intravenous dexketoprofen. Changes in pain intensity were measured by the score on a visual analog scale (VAS) at 30, 60, and 120 minutes and 24 hours after treatment. Efficacy was also assessed by the need for use of an analgesic drug within 24 hours, by readmission with the same complaint to the ED within 72 hours, and by adverse effect rates. MAIN OUTCOME MEASURE: Pain intensity on the VAS scale. SAMPLE SIZE: 148 patients (154 enrolled and treated; 1 patient in the mesotherapy and 5 patients in the systemic therapy group lost to follow up). RESULTS: Pain intensity on the VAS scale decreased from a median score of 8 to 4 in the mesotherapy group and from 8 to 5 in the systemic therapy group. These differences were statistically significant from baseline for all time intervals (P=.001 to 30 minutes, P=.004 to 60 minutes, P=.005 to 120 minutes, and P=.002 to 24 hours). The need to use analgesics and the rate of readmission to the ED were higher in the systemic therapy group (P=.013 and P=.030, respectively). Adverse effect rates were minimal and similar in the study groups during the one-week follow-up period. CONCLUSIONS: Mesotherapy is more efficacious than intravenous dexketoprofen in the management of acute attack of migraine without aura in the ED. LIMITATIONS: Unblinded. Valid for assessing short-term pain relief, but not sufficient to predict long-term efficacy. Not generalizable because single center and small sample size. CONFLICT OF INTEREST: None. REGISTRATION: ClinicalTrials.gov (NCT04519346).