Healthcare resource utilization and associated costs among patients with migraine in Finland: A retrospective register-based study.

Migraine is a common chronic brain disorder, characterized by recurring and often disabling attacks of severe headache, with additional symptoms such as photophobia, phonophobia and nausea. Migraine affects especially the working age population. The objective of this retrospective observational register-based study was to analyze the use of healthcare services and associated costs in Finnish migraine patients. Study was based on aggregate data from January 1st, 2020, to December 31st, 2021, from the Finnish Institute for Health and Welfare's national registries. Patients were grouped into nine patient groups according to medication prescriptions and diagnoses. Healthcare resource utilization in specialty, primary, and occupational healthcare was assessed and analyzed separately for all-cause and migraine related healthcare contacts from a one-year period. The total number of patients was 175 711, and most (45%) of the patients belonged to a group that had used only one triptan. Migraine related total healthcare resource utilization was greater for patients that had used two or more triptans compared to those that had used only one. The patients with three or more preventive medications had the highest total migraine related healthcare resource utilization of the studied patient cohorts. Of the total annual healthcare costs 11.5% (50.6 million €) was associated to be migraine related costs. Total per patient per year healthcare costs were highest with patients that had used three or more preventive medications (5 626 €) and lowest in those with only one triptan (2 257 €). Our findings are in line with the recent European Headache Federation consensus statement regarding the unmet need in patients who have had inadequate response to two or more triptans. When assessing the patient access and cost-effectiveness of novel treatments for the treatment of migraine within different healthcare systems, a holistic analysis of the current disease burden along with potential gains for patients and healthcare service providers are essential information in guiding decision-making.

Coffee consumption and migraine: a population-based study.

Although coffee is one of the most consumed caffeinated beverages worldwide, the role of coffee consumption in migraine is controversial. This study examined the relationship between coffee consumption and clinical characteristics in participants with migraine compared to those with non-migraine headache. This cross-sectional study used data from a nationwide survey on headache and sleep. Coffee consumption was classified as no-to-low (< 1 cup/day), moderate (1-2 cups/day), or high (≥ 3 cups/day). Of the 3030 survey participants, 170 (5.6%) and 1,768 (58.3%) were identified as having migraine and non-migraine headache, respectively. Coffee consumption tended to increase in the order of non-headache, non-migraine headache, and migraine (linear-by-linear association, p = 0.011). Although psychiatric comorbidities (depression for migraine and anxiety for non-migraine headache) and stress significantly differed according to coffee consumption, most headache characteristics and accompanying symptoms did not differ among the three groups for participants with migraine and non-migraine headache. Response to acute headache treatment-adjusted for age, sex, depression, anxiety, stress, preventive medication use, and current smoking-was not significantly different by coffee consumption in participants with migraine and non-migraine headache. In conclusion, most headache-related characteristics and acute treatment response did not significantly differ by coffee consumption in migraine and non-migraine headache.

Changes in pharmacist's recommendations of over-the-counter treatments for the common cold during the COVID-19 pandemic.

BACKGROUND: The common cold is one of the most frequently occurring illnesses worldwide. The aim of this study was to determine which OTC anti-common cold medications were most often recommended by pharmacists and if the COVID-19 pandemic affected such recommendations. METHODS: Non-interventional, observational research trial using a self-developed questionnaire to collect data on pharmacists' recommendations for anti-common cold OTC treatment. The data were collected during the COVID-19 pandemic (December 2021-February 2022) in four large community network pharmacies in Lodz (Poland) and then compared with an analogue period of time before the pandemic (December 2019-February 2020). RESULTS: During COVID-19 pandemic there was a significant (p < 0.05) reduction in paracetamol, acetylsalicylic acid, metamizole magnesium, inosines, alpha-mimetics, mucolytics, homeopathics, and sore throat products and an increase in other tablets/capsules and add-on product recommendations. There was a significant relationship (p < 0.05, OR > 1) between the recommended frequency of paracetamol, inosines, sore throat products (each symptom), metamizole magnesium (headache, fever), acetylsalicylic acid (headache, fever, fatigue), NSAIDs, alpha-mimetics (headache, rhinorrhea), pseudoephedrine (rhinorrhea), homeopathics (headache), herbal products (fatigue), antihistamines (rhinorrhea, cough), and mucolytics (headache, fever, cough). CONCLUSIONS: Favorable prices (before COVID-19 pandemic) and reports on common NSAIDs side effects (beginning of the pandemic) led to high sale of paracetamol. Increased awareness of clinical effectiveness of some medications or their reduced availability influenced their limited recommendations.

Differences in musculoskeletal dysfunctions and in postural alterations between chronic migraine and chronic tension type headache: A cross-sectional study.

OBJECTIVE: The aim of present study is to assess postural alterations and musculoskeletal dysfunctions over all spine in patients with chronic migraine and chronic tension type headache, moreover to highlight the differences between these two forms of primary headache. METHODS: A Cross sectional study was adopted to evaluate the musculoskeletal profile in patients with chronic migraine and with chronic tension type headache. The Bio photogrammetric evaluation was performed using the postural assessment software PAS/SAPO, while unilateral passive accessory intervertebral motion (PAIMs) were applied for manual examinations of spine segments from C0 to L5 vertebra. The One-way Analysis of Variance (ANOVA) test was used to compare the three groups with the software GraphPad InStat 3.06. RESULTS: A total of 60 patients were recruited, 20 for chronic tension type group, 20 for chronic migraine group and 20 healthy controls. The most interesting findings was that patients with chronic primary headaches presented postural alterations in all parameters (cranio-vertebral angle and lumbar-pelvic angle) and musculoskeletal dysfunctions in all spine with respect to healthy controls. Finally, the most clinically relevant finding was that no differences were found between chronic migraine and chronic tension type headache concerning the postural alterations nor the musculoskeletal dysfunctions. CONCLUSION: The sensitization acts as a substrate or consequence of these musculoskeletal dysfunctions in chronic primary headache. Therefore, non-pharmacological treatments targeted in the musculoskeletal system may be a good option in the management of chronic primary headache, especially when these therapies integrate various techniques that involve all spine.

Exploration of the utility of different doses of Qingfei Dayuan granules: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Clinical studies have confirmed that Qingfei Dayuan (QFDY) granules are effective in the treatment of influenza and upper respiratory tract infections (URTIs) caused by pulmonary heat-toxin syndrome (PHTS). Granules of Chinese medicine formulations have become a widely used dosage form in clinical practice. With the continuous optimization of extraction technology, the advantages of Chinese medicine granules have been gradually demonstrated, but the price of Chinese medicine granules is generally higher than that of traditional dosage forms of Chinese medicine, and we support the rational use of the appropriate dosage of QFDY for patients with these conditions. Therefore, we set up half of the conventional dose as the low dose group, and designed the three-arm study to rigorously compare the efficacy difference of low-dose QFDY, QFDY and the placebo group, with the expectation of providing scientific support for the rational selection of the dose and the safe and effective use of the medicine in clinical practice. METHODS: We recruited 108 patients with clinical diagnoses of influenza and URTIs caused by PHTS to receive treatment at six hospitals in Hubei, China. Using a centralized randomization system, patients were randomly assigned at a 1:1:1 ratio to the QFDY, low-dose QFDY, or placebo control groups to receive the corresponding drug, and the study physicians, subjects, outcome assessors, and statisticians were unaware of group assignments. The primary outcome was the time to complete fever relief. Secondary outcomes included the efficacy of Chinese medicine in alleviating signs and symptoms and the disappearance rate of individual symptoms. Adverse events were monitored throughout the trial. RESULTS: A total of 108 patients were recruited. A total of 106 patients were included in the full analysis set (FAS). In the FAS analysis, there was no statistically significant difference in baseline of the three groups before treatment (P > 0.05). 1. Regarding the median time to complete fever relief, the QFDY, low-dose QFDY and placebo groups had median times of 26 h, 40 h and 48 h, respectively. The QFDY group had a shorter time to complete fever relief than the placebo group, and the difference was statistically significant (P < 0.05), while the low-dose QFDY group had a shorter time than the placebo group, but the difference was not statistically significant (P > 0.05). 2. In terms of the total efficacy of Chinese medicine in alleviating symptoms at the end of three full days of treatment, as well as the cure rate of red and sore throat, stuffy and runny nose, and sneezing, QFDY and low-dose QFDY were superior to the placebo, and the differences were statistically significant (P < 0.01). There was no statistical significance in the comparison between the QFDY group and the low-dose QFDY group (P > 0.05). 3. In terms of the headache cure rate after three full days of treatment, QFDY was superior to the placebo, with a statistically significant difference (P < 0.05), and there was no significant efficacy of low-dose QFDY. 4. Safety comparisons showed no serious adverse events and 30 minor adverse events, which were not clinically considered to be related to the drug and were not statistically significant. CONCLUSIONS: In the treatment of patients with influenza and URTIs caused by PHTS, which are mainly characterized by clinical symptoms such as red and sore throat, stuffy and runny nose, and sneezing, when fever is not obvious or low-grade fever is present, the use of low-dose QFDY to simply alleviate the clinical symptoms is recommended and preferred. Moreover, with its good safety profile, QFDY can be used in the treatment of patients with influenza and URTIs caused by PHTS, which can effectively shorten the duration of fever, significantly increase the total efficacy of Chinese medicine in alleviating symptoms after 3 days of treatment, and accelerate the recovery of symptoms such as red and sore throat, stuffy and runny nose, sneezing, and headache, etc. Clinical Trial Registration: http://www.chictr.org.cn. TRIAL NUMBER: ChiCTR2100043449. Registered on 18 February 2021.

The curative efficacy of auricular comprehensive therapy on menstrual migraine and its effect on serum prostaglandin. / è€³ç©´ç»¼åˆç–—æ³•æ²»ç–—æœˆç»æ€§åå¤´ç—›æ‚£è€ ä¸´åºŠç–—æ•ˆåŠå¯¹è¡€æ¸ å‰åˆ—è ºç´ çš„å½±å“.

OBJECTIVES: To observe the curative efficacy of auricular comprehensive therapy on menstrual migraine(MM) and its effect on serum prostaglandin F2α(PGF2α), prostaglandin E2(PGE2) contents and ratio, so as to explore its possible mechanism. METHODS: A total of 66 patients with MM of liver-fire syndrome were randomly divided into observation group (33 cases, 2 cases dropped off) and control group (33 cases, 2 cases dropped off), and 20 healthy women were included in the normal group. Patients in the control group were given flunarizine hydrochloride capsules orally, twice a day, for 3 consecutive weeks. Patients in the observation group were treated with auricular comprehensive therapy, starting 2-5 days before menstrual cramps, once a week, for a total of 3 weeks. The visual analogue scale (VAS) and migraine score were evaluated before and after treatment, and follow-up for 1 and 2 menstrual cycles. Serum PGF2α and PGE2 contents were measured before and after treatment, and the PGF2α/PGE2 ratio was calculated. The clinical effective rates in the two groups were calculated. RESULTS: After treatment and follow-up for 1 and 2 menstrual cycles, the VAS scores, headache degree, the frequency and duration of headache attacks, as well as accompanying symptoms of the observation and control groups were lower than those before treatment(P<0.05), and those of the observation group was lower than those of the control group(P<0.05). Before treatment, the PGF2α contents in the observation and control group were significantly higher(P<0.05), while the PGE2 contents lower(P<0.05) and PGF2α/PGE2 ratio higher(P<0.05) than those in the normal group. After treatment, the serum PGF2α contents in the observation and control group were significantly reduced compared with which before treatment(P<0.05), and were lower in the observation group than that in the control group (P<0.05). The serum PGE2 contents in the observation and control groups were significantly increased after treatment compared with which before treatment(P<0.05), with the contents in the observation group higher than that in the control group(P<0.05). The serum PGF2α/PGE2 ratio in the observation and control group was significantly reduced after treatment compared with which before treatment(P<0.05), with the control group higher than the normal group(P<0.05), and the observation group lower than the control group(P<0.05). The clinical effective rate of the observation group was 93.5% (29/31), and that of the control group was 77.4% (24/31). The effective rate of the observation group was significantly higher than that of the control group(P<0.05). CONCLUSIONS: The curative efficacy of auricular comprehensive therapy on MM with liver-fire syndrome is significantly better than that of oral flunarizine hydrochloride capsules, especially in relieving hea-daches, reducing the frequency and duration of headache attacks, as well as accompanying symptoms. Its mechanism may be related to regulating the abnormal PGF2α and PGE2 contents of patients and reducing the ratio of PGF2α/PGE2.

Pain acceptance as a change mechanism for mindfulness-based cognitive therapy for migraine.

Migraine is one of the leading causes of disability worldwide. Third wave therapies, such as Mindfulness Based Cognitive Therapy for Migraine (MBCT-M), have proven efficacious in reducing headache-related disability. However, research is needed to better understand the change mechanisms involved in these third-wave therapies. Acceptance is a fundamental component of third wave therapies, and more research is warranted on the role of pain acceptance in MBCT-M. It is also valuable to understand the independent roles of the two components of pain acceptance-pain willingness (PW) and activity engagement (AE). The current study is a secondary analysis of a randomized control trial of MBCT-M. Sixty participants were included in the study (MBCT = 31; WL/TAU = 29). Baseline correlations between overall pain acceptance, PW, AE, and headache-related disability were run. Mixed models assessed change from baseline to one-month post-treatment and treatment-by-time interaction for overall pain acceptance, PW, and AE. Mixed models also assessed maintenance of changes at 6-month follow-up in the MBCT-M group. Longitudinal mediation models assessed whether change in pain acceptance, PW, and AE mediated the relationship between treatment and change in headache-related disability. Pain acceptance, PW, and AE were all negatively correlated with headache-related disability at baseline. Pain acceptance, PW, and AE all significantly increased over time in both the waitlist/ treatment-as-usual group (WL/TAU) and the MBCT-M group. Only AE increased more in the MBCT group than the WL/TAU group. Change in pain acceptance, PW, and AE all significantly mediated the relationship between MBCT and change in headache-related disability. The study supports the importance of pain acceptance, specifically the activity engagement component, in MBCT-M.

Effects on temporomandibular disorder in the treatment of tension-type headache with acupuncture and therapeutic exercises. A secondary analysis from a randomized controlled trial.

OBJECTIVES: To examine the effects of acupuncture and therapeutic exercise alone and in combination on temporomandibular joint symptoms in tension-type headache and to evaluate the potential interaction of existing temporomandibular dysfunction on the success of headache treatment. DESIGN: Pre-planned secondary analysis of a randomized controlled, non-blinded trial. SETTING: Outpatient clinic of a German university hospital. SUBJECTS: Ninety-six Participants with frequent episodic or chronic tension-type headache were randomized to one of four treatment groups. INTERVENTIONS: Six weeks of acupuncture or therapeutic exercise either as monotherapies or in combination, or usual care. Follow-up at 3 and 6 months. MAIN MEASURES: Subjective temporomandibular dysfunction symptoms were measured using the Functional Questionnaire Masticatory Organ, and the influence of this sum score and objective initial dental examination on the efficacy of headache treatment interventions was analyzed. RESULTS: Temporomandibular dysfunction score improved in all intervention groups at 3-month follow-up (usual care: 0.05 [SD 1.435]; acupuncture: -5 [SD 1.436]; therapeutic exercise: -4 [SD 1.798]; combination: -3 [SD 1.504]; P = 0.03). After 6 months, only acupuncture (-6 [SD 1.736]) showed a significant improvement compared to the usual care group (P < 0.01). Subjective temporomandibular dysfunction symptoms had no overall influence on headache treatment. CONCLUSIONS: Only acupuncture had long-lasting positive effects on the symptoms of temporomandibular dysfunction. Significant dental findings seem to inhibit the efficacy of acupuncture for tension-type headache.

Effect of photobiomodulation therapy on headache, and fatigue in patients with chronic rhinosinusitis: a randomized controlled study.

Chronic rhinosinusitis (CRS) is a debilitating disease that resists medical treatment. Photobiomodulation therapy is one of the promising treatment modalities for CRS. The purpose is to investigate the effect of photobiomodulation therapy on headache, fatigue, sinus opacification, and ostiomeatal complex obstruction in patients with CRS. Thirty-one patients with CRS were randomly divided into photobiomodulation therapy and control groups. The photobiomodulation therapy group received photobiomodulation therapy (2.5 J, frequency 9.12 Hz, and 904 nm for 10 min for 12 sessions) on eight rhinosinusitis sites, and the control group received a sham laser. Headache, fatigue, and sinus opacification outcomes were measured before and after treatment. There was a significant improvement in headache, fatigue, and sinus opacification in the photobiomodulation therapy group in comparison with the control group (p < 0.05). Photobiomodulation therapy is an effective physical therapy treatment modality for the management of CRS.Clinical trial registry: NCT05861817.

Exploration of the methods and rules of syndrome/pattern differentiation and treatment of headache from the acupuncture-moxibustion prescriptions of ancient literature based on the data mining technology. / 基于数据挖掘技术探析古代头痛针灸方的辨治方法与规律.

The study aims to identifying and exploring the methods and rules of the syndrome/pattern differentiation and treatment of headache through collating acupuncture-moxibustion prescriptions recorded earliest in ancient literature. Using Excel2016 software, the structural data table was prepared with "name of disease", "location of disease", "etiology and pathogenesis", "complicated symptoms", "sites for acupuncture and moxibustion" and "techniques of acupuncture and moxibustion" included. The normative approach was conduced on "name of disease", "etiology and pathogenesis", "complicated symptoms" and "nomenclature of acupoint". Using conventional literature statistical method, combined with Apriori algorithm of association rule, the implicit multi-dimensional correlation rules were explored among various elements of syndrome/pattern differentiation of headache and corresponding therapeutic methods. Based on the findings of the study, the regularity was distinct regarding the treatment at "distal acupoints along the affected meridian and the local acupoints at the affected area" after identifying the location of headache; the strong association was presented between "etiology and pathogenesis" and "acupoint selection", and between "etiology and pathogenesis" and "therapeutic methods", including 9 and 12 rules, respectively. Guanyuan (CV 4) selected in treatment of headache was associated with kidney deficiency, the combination of Zhongwan (CV 12) and Zusanli (ST 36) was with phlegm, Fengfu (GV 16), Fengchi (GB 20), Xinghui (GV 22) and Baihui (GV 20) was with wind, and Hegu (LI 4) was with cold. Moxibustion was dominant in treatment if headache was caused by pathogenic cold or related to deficiency syndrome; acupuncture was used specially for the case caused by phlegm, or interaction of wind and phlegm or wind and heat. For heat syndrome, either acupuncture or moxibustion was applicable, in general, acupuncture was more commonly used in comparison with moxibustion for headache. There were 6 association rules regarding the acupoint selection and the techniques of acupuncture and moxibustion. Moxibustion was generally applied to Xinghui (GV 22), Shangxing (GV 23) and Baihui (GV 20) ; and acupuncture was to Fengfu (GV 16), Hegu (LI 4) and Zusanli (ST 36). There were few association rules between the complicated symptoms and acupoint selection. Among nearly 100 complications, there were only 3 feature associations. Zhongwan (CV 12) was selected for the case with poor appetite, Chengjiang (CV 24) was with neck stiffness, and Fengchic (GB 20) combined with Fenglong (ST 40) or Jiexi (ST 41) was used if vertigo was present. In the ancient time, regarding the treatment of headache, acupuncture and moxibustion are delivered based on the three aspects, i.e. the location of illness, the etiology and pathogenesis, and the complicated symptoms. For acupoint selection, in line with the courses of affected meridians, the adjacent and distal acupoints are combined according to the location of headache. The acupoint prescription is composed in terms of the etiology and pathogenesis. The techniques of acupuncture and moxibustion are optimized in consideration of the sites where acupuncture and moxibustion are operated.

Nutraceuticals in migraine.

Nutraceuticals represent substances derived from food or plants that provide medical or health benefits, and are increasingly sought by patients as a means of treating migraine in a natural, effective, and safe manner as conventional therapies often fail, are expensive, and laden with side effects. This chapter reviews various nutraceutical therapies for migraine including phytomedicines (plant-based therapies), diets for migraine management and vitamin, mineral, and supplement-based treatments for migraine with respect to preclinical and clinical evidence. Reviewed herein are a multitude of nutraceutical options for the treatment of migraine including vitamins (e.g., riboflavin), antioxidants, and plants/phytomedicines: feverfew, butterbur, cannabis, St. John's Wort, Rosa x damascena, and Gingko biloba. Dietary interventions for migraine include low lipid, vegan, ketogenic, and DASH (dietary approaches to stop hypertension). Supplements such as polyunsaturated fatty acids (PUFAs) as well as l-carnitine, pre/probiotics, and melatonin are also discussed. Migraine patients and their caregivers have an armamentarium of nutraceutical options to treat headache. While some therapies such as vitamins harbor stronger evidence with more rigorous studies, patients may also choose dietary therapies that may offer more systemic health benefits while also improving migraine. As cannabis legalization spreads worldwide, care providers must be aware of the limited evidence in migraine. Future studies may explore traditional ancient medicines for migraine at basic science and clinical level, while currently adopted and new nutraceutical treatments may benefit from partnership with industry to engage in larger trials in humans.

Biobehavioral treatments of migraine.

Pharmacotherapies are the mainstays of migraine management, though it is not uncommon for them to be poorly tolerated, contraindicated, or only modestly effective. There is a clear need for nonpharmacologic migraine therapies, either employed alone or in combination with pharmacotherapies. Behavioral and psychosocial factors known to contribute to the onset, exacerbation, and persistence of primary headache disorders (e.g., stress, sleep, diet) serve as targets within a self-management model for migraine-a model that features headache pharmacotherapies, behavioral skills training, medication adherence facilitation, relevant lifestyle changes, and techniques to limit headache-related impairment. Behavioral self-management interventions for migraine with the strongest empirical validation (e.g., relaxation training, biofeedback training, cognitive-behavior therapies) presently are available in specialty headache treatment centers and routinely show promise for reducing headache pain frequency/severity and related impairment, reducing reliance on pharmacotherapies, enhancing personal control over headache activity, and reducing headache-related distress and symptoms. These approaches may be particularly well-suited among patients for whom pharmacotherapies are unwanted, poorly tolerated, or contraindicated. Though underutilized, clinical trials indicate that new and well-established behavioral therapies are similarly effective to migraine medications for migraine prevention among adults and can be successfully employed in various settings.

Physical treatment of migraine.

Physical modalities, including acupuncture, massage therapy, physical therapy, and spinal manipulation, are commonly sought for migraine headache management. Acupuncture has been helpful in management of migraine, particularly as an adjunct to standard therapy. Some studies support acupuncture in combination with electroacupuncture and a traditional Chinese medicine form of massage called tuina as beneficial. An estimated 15% of patients with migraine seek spinal manipulation with osteopathic physicians or chiropractors, though evidence of benefit is lacking and potential for adverse effects is low but present. Studies of massage therapy in migraine have been heterogeneous and of low quality, often combined with other manual therapies to show effect. While manual therapies appear to reduce pain and improve quality of life, further study is needed to determine which specific types of manual therapy are most effective. While exercise is good for all patients, specific migraine management with physical therapy and regular exercise is not supported by evidence. Nevertheless, these modalities should be considered in certain situations when performed by trained and licensed professionals.

Regulation of headache response and transcriptomic network by the trigeminal ganglion clock.

OBJECTIVE: To characterize the circadian features of the trigeminal ganglion in a mouse model of headache. BACKGROUND: Several headache disorders, such as migraine and cluster headache, are known to exhibit distinct circadian rhythms of attacks. The circadian basis for these rhythmic pain responses, however, remains poorly understood. METHODS: We examined trigeminal ganglion ex vivo and single-cell cultures from Per2::LucSV reporter mice and performed immunohistochemistry. Circadian behavior and transcriptomics were investigated using a novel combination of trigeminovascular and circadian models: a nitroglycerin mouse headache model with mechanical thresholds measured every 6 h, and trigeminal ganglion RNA sequencing measured every 4 h for 24 h. Finally, we performed pharmacogenomic analysis of gene targets for migraine, cluster headache, and trigeminal neuralgia treatments as well as trigeminal ganglion neuropeptides; this information was cross-referenced with our cycling genes from RNA sequencing data to identify potential targets for chronotherapy. RESULTS: The trigeminal ganglion demonstrates strong circadian rhythms in both ex vivo and single-cell cultures, with core circadian proteins found in both neuronal and non-neuronal cells. Using our novel behavioral model, we showed that nitroglycerin-treated mice display circadian rhythms of pain sensitivity which were abolished in arrhythmic Per1/2 double knockout mice. Furthermore, RNA-sequencing analysis of the trigeminal ganglion revealed 466 genes that displayed circadian oscillations in the control group, including core clock genes and clock-regulated pain neurotransmitters. In the nitroglycerin group, we observed a profound circadian reprogramming of gene expression, as 331 of circadian genes in the control group lost rhythm and another 584 genes gained rhythm. Finally, pharmacogenetics analysis identified 10 genes in our trigeminal ganglion circadian transcriptome that encode target proteins of current medications used to treat migraine, cluster headache, or trigeminal neuralgia. CONCLUSION: Our study unveiled robust circadian rhythms in the trigeminal ganglion at the behavioral, transcriptomic, and pharmacogenetic levels. These results support a fundamental role of the clock in pain pathophysiology. PLAIN LANGUAGE SUMMARY: Several headache diseases, such as migraine and cluster headache, have headaches that occur at the same time each day. We learned that the trigeminal ganglion, an important pain structure in several headache diseases, has a 24-hour cycle that might be related to this daily cycle of headaches. Our genetic analysis suggests that some medications may be more effective in treating migraine and cluster headache when taken at specific times of the day.

Daith piercing: Revisited from the perspective of auricular acupuncture systems. A narrative review.

BACKGROUND: Daith piercing is a special ear-piercing method that punctures the crus of the helix. The penetrated site at the ear's innermost point is assumed to stimulate a pressure point associated with the vagus nerve. It has been reported that the pierced spot relieves migraine and tension-type headaches by activating vagal afferents, leading to the inhibition of neurons in the caudal trigeminal nucleus via the nucleus tractus solitarii. OBJECTIVE: The objective of this narrative literature review is to summarize the current state of knowledge concerning daith piercing for the treatment of migraine and tension-type headaches from the perspectives of the Chinese and Western auricular systems. METHODS: PubMed and China National Knowledge Infrastructure databases were searched using the keywords "daith piercing," "auricular points," "headache," and "acupuncture" from database inception to September 1, 2023. Only studies on humans were eligible; otherwise, no further restrictions were applied to the study designs, type of headache, or patient population of the identified articles. Bibliographies of all eligible studies were screened for further eligible studies. The main outcome of interest was a quantitative measure of pain relief by daith piercing. Secondary outcomes were relapse time of headache and further outcomes related to daith piercing, if available. RESULTS: From a total of 186 identified articles, one retrospective study and three case reports fulfilled the inclusion criteria. No clinical trial was identified. The obtained studies describe patients experiencing chronic headaches undergoing daith piercing without changing or reducing their usual medication. In all case studies and the retrospective study, patients reported substantial reductions in pain immediately after daith piercing; however, headache symptoms recurred several weeks to months thereafter. From the perspective of the Chinese and Western auricular systems, no sufficient explanation for the described treatment effect of daith piercing was found. CONCLUSION: The available literature, combined with the reported recurrence of pain as well as the associated side effects of daith piercing, indicate that current evidence does not support daith piercing for the treatment of migraine, tension-type headaches, or other headache disorders. PLAIN LANGUAGE SUMMARY: This paper summarizes what we know about Daith piercing (DP) for chronic migraine and tension-type headache and discusses how DP might work. Current evidence does not support DP as an effective treatment of chronic migraine and tension-type headache. These findings might assist clinicians in discussing this subject with patients as well as guide future research.

A superficial dissection approach to the sphenopalatine (pterygopalatine) ganglion to emphasize osteopathic clinical relevance.

The sphenopalatine (pterygopalatine) ganglion (SPG) is the most superficial ganglia to manipulate from the oral cavity. It has parasympathetic and sensory fibers directly affecting the paranasal sinuses as well as the palatine, nasal, pharyngeal, and lacrimal glands. The SPG can be manipulated intraorally by students and physicians utilizing osteopathic manipulative treatment (OMT) to relieve congestion associated with sinusitis, allergies, headaches, and upper respiratory infections. Within osteopathic medical education programs, students have anecdotally had difficulty identifying this ganglion due to its deep anatomic location and lack of direct visualization. In this article, we discuss that cadaveric dissection with a superficial to deep approach to the SPG has the ability to allow medical students and physicians to better understand the three-dimensional location and osteopathic clinical relevance of this ganglion.

Involvement of the ipsilateral-to-the-pain anterior-superior hypothalamic subunit in chronic cluster headache.

BACKGROUND: Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition. METHODS: We used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models. Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients. RESULTS: Patients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior-superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found. CONCLUSIONS: We identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.

Involvement of Plasma Melatonin in Medication-Overuse Headache: A Cross-Sectional Study.

OBJECTIVES: Patients with medication-overuse headache (MOH) are often complicated with anxiety, depression, and sleep disorders and are associated with dependence behavior and substance abuse. Melatonin has physiological properties including analgesia, regulation of circadian rhythms, soporific, and antidepressant and affects drug preference and addiction. This study aimed to investigate the role of melatonin in MOH compared with episodic migraine (EM) and healthy controls and to verify the relationship between plasma melatonin levels and psychiatric symptoms. METHODS: Thirty patients affected by MOH, 30 patients with EM, and 30 matched healthy controls were enrolled. All subjects completed a detailed headache questionnaire and scales including the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index, the Leeds Dependence Questionnaire. Melatonin levels in plasma samples were measured by enzyme immunoassay method. RESULTS: The levels of plasma melatonin were significantly different among 3 groups of subjects (MOH, 7.74 [5.40-9.89]; EM, 9.79 [8.23-10.62]; Control, 10.16 [8.60-17.57]; H = 13.433; P = 0.001). Significantly lower levels of melatonin were found in MOH patients compared with healthy controls ( P = 0.001). The level of plasma melatonin inversely correlated with the scores of HADS-Anxiety ( r = -0.318, P = 0.002), HADS-Depression ( r = -0.368, P < 0.001), Pittsburgh Sleep Quality Index ( r = -0.303, P = 0.004), and Leeds Dependence Questionnaire ( r = -0.312, P = 0.003). CONCLUSIONS: This study innovatively detects the plasma melatonin levels in MOH patients and explores the association between melatonin levels and psychiatric symptoms. Melatonin may be potential complementary therapy in the treatment of MOH considering its comprehensive role in multiple aspects of MOH.

Physical Therapist Interventions to Reduce Headache Intensity, Frequency, and Duration in Patients With Cervicogenic Headache: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: The aim of this study was to assess the efficacy of physical therapist interventions on the intensity, frequency, and duration of headaches, as well as on the quality of life of patients with cervicogenic headache. METHODS: The following databases were searched up to October 2022: Physiotherapy Evidence Database, Web of Science, Pubmed, and Cochrane Library. Randomized controlled trials assessing the effect of physical therapist interventions on adults with cervicogenic headache were included. Quality appraisal was conducted using the Cochrane risk of bias 2.0 tool and the Confidence in Network Meta-analysis web app. Synthesis methods were conducted in accordance with the Cochrane Handbook. RESULTS: Of the 28 identified reports, 23 were included in the quantitative synthesis. Manipulation plus dry needling was the highest-ranked intervention to reduce the short-term headache intensity (mean difference [MD] = -4.87; 95% CI = -8.51 to -1.24) and frequency (MD = -3.09; 95% CI = -4.93 to -1.25) when compared to a control intervention. Other high-ranked and clinically effective interventions (when compared to a control intervention) were muscle-energy technique plus exercise (MD = 4.37; 95% CI = -8.01 to -0.74), as well as soft tissue techniques plus exercise (MD = -3.01; 95% CI = -5.1 to -0.92) to reduce short-term headache intensity, and dry needling plus exercise (MD = -2.92; 95% CI = -4.73 to -1.11) to reduce short-term headache frequency. These results were based on a low certainty of evidence. CONCLUSION: The 4 most highly ranked interventions can be considered in clinical practice. However, no conclusive recommendation can be made due to the low certainty of evidence. IMPACT: Combined interventions such as spinal joint manipulation plus dry needling and muscle-energy technique or soft tissue techniques or dry needling plus exercises seem to be the best interventions to reduce short-term cervicogenic headache intensity and/or frequency.

Clinical Effectiveness of Craniosacral Therapy in Patients with Headache Disorders: A Systematic Review and Meta-analysis.

OBJECTIVES: To analyze the effectiveness of craniosacral therapy in improving pain and disability among patients with headache disorders. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Physiotherapy Evidence Database, Scopus, Cochrane Library, Web of Science, and Osteopathic Medicine Digital Library databases were searched in March 2023. REVIEW METHODS: Two independent reviewers searched the databases and extracted data from randomized controlled trials comparing craniosacral therapy with control or sham interventions. The same reviewers assessed the methodological quality and the risk of bias using the PEDro scale and the Cochrane Collaboration tool, respectively. Grading of recommendations, assessment, development, and evaluations was used to rate the certainty of the evidence. Meta-analyses were conducted using random effects models using RevMan 5.4 software. RESULTS: The searches retrieved 735 studies, and four studies were finally included. The craniosacral therapy provided statistically significant but clinically unimportant change on pain intensity (Mean difference = -1.10; 95% CI: -1.85, -0.35; I2: 44%), and no change on disability or headache effect (Standardized Mean Difference = -0.34; 95% CI -0.70, 0.01; I2: 26%). The certainty of the evidence was downgraded to very low. CONCLUSION: Very low certainty of evidence suggests that craniosacral therapy produces clinically unimportant effects on pain intensity, whereas no significant effects were observed in disability or headache effect.