Research Progress on the Experimental Model and Underlying Mechanistic Studies of Tension-Type Headaches.

PURPOSE OF REVIEW: Tension-type headaches (TTH) significantly diminish patients' quality of life and increase absenteeism, thereby imposing a substantial economic burden. Animal models are essential tools for studying disease mechanisms and drug development. However, until now, little focus has been placed on summarizing the animal models of TTH and associated mechanistic studies. This narrative review discusses the current animal models of TTH and related mechanistic studies to provide insights into the pathophysiological mechanisms of and treatments for TTH. RECENT FINDINGS: The primary method for constructing an animal model of TTH involves injecting a solution of pain relievers, such as adenosine triphosphate, nerve growth factor, or a high concentration of salt solution, into the neck to initiate harmful cervical muscle responses. This model enables the examination of the interaction between peripheral muscles and central sensitization, which is crucial for understanding the pathophysiology of TTH. Mechanistic studies based on this model have investigated the effect of the P2X receptor antagonist, P2X7 receptor blockade, the P2Y1 receptor agonist 2-MESADP, P2Y1 receptor antagonist MRS2179, nitric oxide synthase inhibitors, and acetylsalicylic acid. Despite notable advancements, the current model of TTH has limitations, including surgical complexity and the inability to replicate chronic tension-type headache (CTTH). To gain a more comprehensive understanding and develop more effective treatment methods, future studies should focus on simplifying surgical procedures, examining other predisposing factors, and establishing a model for chronic TTH. This will offer a deeper insight into the pathophysiological mechanism of TTH and pave the way for improved treatment approaches.

Primary headaches among gender dysphoric female-to-male individuals: A cross-sectional survey on gender transition experience.

OBJECTIVE: To investigate the frequency, attack characteristics, and treatment experiences of migraine and tension-type headache (TTH) among gender dysphoric female-to-male (FtM) participants as well as in relation to psychiatric comorbidities and real-life experience that relates to being transgender in Turkey. BACKGROUND: There are only a few publications to date on transgender individuals with headache. Further studies to understand the distinctive needs might provide better management. METHODS: A total of 88 gender dysphoric FtM individuals (mean (SD) age: 24.8 (5.7) years) were included on a voluntary basis in this cross-sectional survey. Each participant filled out the questionnaire form that elicited items on sociodemographic characteristics, Gender Identity Transition Inventory, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Headache Questionnaire. RESULTS: Overall, 32/88 (36.4%; 95% confidence interval [CI]: 27.0%-47.0%) participants were diagnosed with migraine, and 36/88 (40.9%; 95% CI: 31.5%-52.3%) participants were diagnosed with TTH. High rates of unemployment, smoking, and social drinking were observed in our sample compared with the general population in Turkey. The three-item ID migraine screener was positive in 20.5% (18/88 patients) of our population. Patients with migraine in comparison with patients with TTH had statistically significantly higher BDI [12.0 (1-50) vs. 7.0 (0-33); p = 0.013] and BAI [13 (1-48) vs. 5 (0-22); p = 0.016] scores, longer headaches in the past month [median 3 vs. 1 day; p < 0.001], higher Numerical Rating Scale scores for headache severity [7 (2-10) vs. 5 (1-9), p < 0.001], and higher likelihood of menstruation acting as a triggering factor [8/32 patients (25.0%) vs. 0/36 patients (0.0%); p = 0.001] as well as increased rates of previously given diagnosis by a physician [15/32 patients (46.9%) vs. 4/36 patients (11.1%); p < 0.001], a greater number of neuroimaging tests being performed [12/32 patients (37.5%) vs. 3/36 patients (9.1%); p = 0.012], and a higher rate of emergency room utilization [7/32 patients (21.9%) vs. 1/36 patients (2.8%); p = 0.039] for headache. CONCLUSIONS: In the FtM transgender population we investigated, migraine and TTH were quite common. The screening and early recognition of comorbid migraine, as well as the comorbid depression and anxiety, seem to be important in gender dysphoric FtM individuals. Further studies are needed to better understand the potential interaction of migraine with comorbid psychiatric disorders and the prevalence of headache types and gender-affirmative hormone treatment outcomes in the transgender population.

Constipation is associated with tension type headache in women / Constipação está associada à cefaleia do tipo tensional em mulheres

ABSTRACT Tension-type headaches (TTH) and irritable bowel syndrome (IBS) are comorbid diseases affecting, especially, women. One of the underlying mechanisms for both is autonomic dysfunction in the brain-gut axis. We aimed to evaluate the factors accompanying TTH and their relation to functional gastrointestinal disorders. Methods: Women diagnosed with TTH were questioned about headache pattern and severity, and accompanying factors, as well as being screened for IBS according to the Rome III criteria. The participants were divided into two groups: constipation-dominant IBS (IBS-C) group and "others", with a total of 115 individuals included in the study. Results: Of the 115 patients; 48 (41.8%) of the women had IBS-C criteria while 67 (58.2%) described mixed-type IBS or diarrhea-dominant IBS. There were no significant differences in terms of mean age (p = 0.290), body mass index (p = 0.212), visual analog scale (p = 0.965), duration of attacks (p = 0.692), and episodic/chronic type (p = 0.553). Osmophobia was seen in 43.5%; phonophobia in 68.7%, and photophobia in 47.0% of the patients, and only osmophobia was significantly associated in women in the IBS-C group (p = 0.001). Conclusion: In female patients with TTH, a higher level of constipation was detected. The relationship of these two diseases suggests that they may share common mechanisms. This is the first study showing the relationship of osmophobia with constipation.

RESUMO As cefaléias do tipo tensional (TTH) e a síndrome do intestino irritável (IBS) são comorbidades que afetam especialmente as mulheres. O mecanismo subjacente para ambas é a disfunção autonômica no eixo cérebro-intestino. Nosso objetivo foi avaliar os fatores que acompanham as TTH e sua relação com distúrbios gastrointestinais funcionais (FGID). Métodos: Mulheres com diagnóstico de TTH foram questionadas quanto ao padrão e gravidade da cefaleia, fatores acompanhantes e triadas para IBS de acordo com os critérios de Roma III e foram divididas em dois grupos: grupo com IBS com predominância de constipação (IBS-C) e as demais. Um total de 115 mulheres foram incluídas no estudo. Resultados: Do total de 115 pacientes; 48 (41,8%) das mulheres tiveram os critérios da IBS-C, enquanto 67 (58,2%) tiveram IBS do tipo misto ou IBS com predominância de diarreia. Não houve diferenças significativas em termos de idade média (p = 0,290), índice de massa corporal (IMC) (p = 0,212), escala visual analógica (VAS) (p = 0,965), duração dos ataques (p = 0,692), e tipo episódico / crônico (p = 0,553). Osmofobia foi observada em 43,5% das pacientes; fonofobia em 68,7% e fotofobia em 47,0%, e apenas osmofobia foi significativamente associada no grupo de mulheres com predominância de constipação (p = 0,001). Conclusão: Em pacientes do sexo feminino com TTH, encontra-se uma maior constipação. A relação dessas duas doenças sugere que elas podem compartilhar mecanismos comuns. Além disso, este é o primeiro estudo mostrando a relação da osmofobia com a constipação.

Myofascial trigger points in migraine and tension-type headache.

BACKGROUND: A myofascial trigger point is defined as a hyperirritable spot in skeletal muscle that is associated with a hypersensitive palpable nodule in a taut band. It has been suggested that myofascial trigger points take part in chronic pain conditions including primary headache disorders. The aim of this narrative review is to present an overview of the current imaging modalities used for the detection of myofascial trigger points and to review studies of myofascial trigger points in migraine and tension-type headache. FINDINGS: Different modalities have been used to assess myofascial trigger points including ultrasound, microdialysis, electromyography, infrared thermography, and magnetic resonance imaging. Ultrasound is the most promising of these modalities and may be used to identify MTrPs if specific methods are used, but there is no precise description of a gold standard using these techniques, and they have yet to be evaluated in headache patients. Active myofascial trigger points are prevalent in migraine patients. Manual palpation can trigger migraine attacks. All intervention studies aiming at trigger points are positive, but this needs to be further verified in placebo-controlled environments. These findings may imply a causal bottom-up association, but studies of migraine patients with comorbid fibromyalgia syndrome suggest otherwise. Whether myofascial trigger points contribute to an increased migraine burden in terms of frequency and intensity is unclear. Active myofascial trigger points are prevalent in tension-type headache coherent with the hypothesis that peripheral mechanisms are involved in the pathophysiology of this headache disorder. Active myofascial trigger points in pericranial muscles in tension-type headache patients are correlated with generalized lower pain pressure thresholds indicating they may contribute to a central sensitization. However, the number of active myofascial trigger points is higher in adults compared with adolescents regardless of no significant association with headache parameters. This suggests myofascial trigger points are accumulated over time as a consequence of TTH rather than contributing to the pathophysiology. CONCLUSIONS: Myofascial trigger points are prevalent in both migraine and tension-type headache, but the role they play in the pathophysiology of each disorder and to which degree is unclarified. In the future, ultrasound elastography may be an acceptable diagnostic test.

Hints on Diagnosing and Treating Headache.

BACKGROUND: Headache, like dizziness, is one of the more common presenting complaints in outpatient care and in the emergency room. More than 200 varieties of headache have been described, and the false impression may arise that the diagnosis and treatment of these syndromes is a highly challenging task. METHODS: This review is based on pertinent articles retrieved by a selective search in PubMed. RESULTS: In primary headache, the headache is not a symptom but a disease in its own right. There are four types of primary headache: migraine, tension headache, trigeminal autonomic cephalalgia, and other primary headache disorders. By definition, the physical examination is normal, including the neurological examination. Secondary headache, in contrast, is a symptom of another disease (e.g., a tumor or cerebral hemorrhage). Triptans and nonsteroidal anti-inflammatory drugs (NSAID) are the drugs usually given for the acute treatment and prophylaxis of migraine. In tension headache, NSAID are given acutely, and tricyclic drugs for prophylaxis. There are various options for the treatment of trigeminal autonomic cephalalgia syndromes such as cluster headache and paroxysmal hemicrania. For group 4 headaches (other primary headache disorders), the treatment must be chosen on an individual basis; indomethacin is often effective. CONCLUSION: If the patient is clearly suffering from none of the four types of primary headache, the problem must be a headache of a secondary nature, potentially reflecting a dangerous underlying disease. The treatment of headache is usually successful and thus highly rewarding for physicians of all medical specialties.

Neurotrophic factors in tension-type headache / Fatores neurotróficos na cefaleia do tipo tensional

Neurotrophic factors (NF) are involved in pain regulation and a few studies have suggested that they may play a pathophysiological role in primary headaches. The aim of this study was to investigate NF levels in patients with tension type headache (TTH). We carried out a cross sectional study including 48 TTH patients and 48 age and gender matched controls. Beck Depression and Anxiety Inventories, and Headache Impact Test were recorded. Serum levels of NF were determined by ELISA. There were not significant differences between NF levels between TTH patients and controls. Patients with chronic and episodic TTH had not significant differences in NF levels. The presence of headache at the time of evaluation did not significantly alter the levels of NF. Depression and anxiety scores as well as headache impact did not correlate with NF levels. Our study suggest that the serum levels of NF are not altered in TTH.

Os fatores neurotróficos (FN) participam da regulação da dor e podem ter um papel na fisiopatologia das cefaleias peimárias. O objetivo do presente estudo foi avaliar os níveis séricos de FN em pacientes com cefaleia do tipo tensional (CTT). Foi realizado corte transversal com 48 pacientes com CTT e 48 controles pareados por gênero e idade. Os inventários de Beck para depressão e ansiedade, bem como o inventário de impacto da cefaleia foram aplicados. Os níveis séricos de FN foram determinados por ELISA. Não houve diferenças significativas entre níveis de FN entre pacientes com TTH e controles, bem como entre pacientes com TTH episódica e crônica. Presença de cefaleia no momento da avaliação não alterou os níveis séricos de FN. Os escores de depressão, ansiedade e impacto da cefaleia não se correlacionaram com os níveis de FN. Nosso estudo sugere que não há alteração dos níveis de FN na TTH.

Evaluation of the changes in the nasal cavity during the migraine attack.

OBJECTIVES: There are some subjective symptoms involving the nasal cavity such as nasal congestion during a migraine attack. In this study, we aimed to evaluate the possible changes occurring in the nasal cavity during headache in patients with migraine. MATERIALS AND METHODS: Patients with migraine were studied. The control group consisted of patients with tension-type headache. The severity of the headache and accompanying complaints were assessed using visual analog scale, and the nasal mucosa was assessed through anterior rhinoscopy and endoscopy. Resistance of the nasal cavity was evaluated through anterior rhinomanometry. Data obtained during the attack periods and attack-free periods were compared. RESULTS: Twenty-five patients with migraine and 15 patients with tension-type headache were enrolled. It was found that 19 patients (76%) of the group with migraine and 5 patients of the group with tension-type headache were experiencing nasal congestion during the attack and that the differences between the groups were statistically significant (P < 0.05). The average of total nasal resistance in the patients with migraine was 0.57 ± 0.60 kPa/L/sn during migraine attacks and 0.28 ± 0.14 kPa/L/sn during attack-free periods. The average of total nasal resistance in the patients with tension-type headache was 0.32 ± 0.14 kPa/L/sn during attack periods and 0.31 ± 0.20 kPa/L/sn during attack-free periods. In the group with migraine, the change of nasal resistance between during the attack and attack-free periods was found statistically significant, whereas there was no statistically significant difference in the group with tension-type headache. CONCLUSIONS: According to the results of this study, complaints regarding nasal obstruction and nasal airway resistance increase during migraine attacks. Cause-and-effect relationship between nasal obstruction and pain is not clear, and clinical trials are needed to determine the effect of nasal obstruction treatment (mucosal decongestion, etc) on the complaint of pain.

Sistema trigémino vascular y cefalea / Trigeminovascular System and Primary Headache

La fisiopatología de las cefaleas primarias es compleja e incluye un sinnúmerode interacciones que regulan el proceso nociceptivo. Dentro de los principalesresponsables de generar el dolor se encuentra el sistema trigémino vascular, que esun conjunto de estructuras que integran vías tanto centrales corticosubcorticales comoperiféricas, que desempeñan un papel activo no solo en la génesis del dolor, sino enlas manifestaciones autonómicas y visuales que acompañan la cefalea. Así mismo, estesistema es el responsable de los mecanismos de sensibilización central característicosdel dolor. En el artículo se desarrollan brevemente las principales estructuras queparticipan en la génesis de las cefaleas primarias y sus interacciones en las diferentespartes del sistema nervioso...

The pathophysiology of primary headache iscomplex and it includes several interactionsthat regulate the nociceptive process. The trigeminal-vascular system is perhaps one of theprincipal structures that generate pain due tothe integration of several pathways both centraland peripheral. In addition to this, the trigeminalvascular system also plays a central role inthe autonomic and visual symptoms that affectindividuals with headache and in the centralsensitization process. In this article we brieflydiscuss the main structures that participate in thepathophysiology of primary headaches and theirinteractions in the different levels of the centralnervous system...

Surgical desensitisation of the mechanoreceptors in Müller's muscle relieves chronic tension-type headache caused by tonic reflexive contraction of the occipitofrontalis muscle in patients with aponeurotic blepharoptosis.

Proprioceptively innervated intramuscular connective tissues in Müller's muscle function as exterior mechanoreceptors to induce reflex contraction of the levator and occipitofrontalis muscles. In aponeurotic blepharoptosis, since the levator aponeurosis is disinserted from the tarsus, stretching of the mechanoreceptors in Müller's muscle is increased even on primary gaze to induce phasic and tonic reflexive contraction of the occipitofrontalis muscle. It was hypothesised that in certain patients with aponeurotic blepharoptosis, the presence of tonic reflexive contraction of the occipitofrontalis muscle due to the sensitised mechanoreceptors in Müller's muscle, can cause chronic tension-type headache (CTTH) associated with occipitofrontalis tenderness. To verify this hypothesis, this study evaluated (1) what differentiates patients with CTTH from patients without CTTH, (2) how pharmacological contraction of Müller's smooth muscle fibres as a method for desensitising the mechanoreceptors in Müller's muscle affects electromyographic activity of the frontalis muscle, and (3) how surgical aponeurotic reinsertion to desensitise the mechanoreceptors in Müller's muscle electromyographically or subjectively affects activities of the occipitofrontalis muscle or CTTH. It was found that patients had sustained CTTH when light eyelid closure did not markedly reduce eyebrow elevation. However, pharmacological contraction of Müller's smooth muscle fibres or surgery to desensitise the mechanoreceptor electromyographically reduced the tonic contraction of the occipitofrontalis muscle on primary gaze and subjectively relieved aponeurotic blepharoptosis-associated CTTH. Over-stretching of the mechanoreceptors in Müller's muscle on primary gaze may induce CTTH due to tonic reflexive contraction of the occipitofrontalis muscle. Therefore, surgical desensitisation of the mechanoreceptors in Müller's muscle appears to relieve CTTH.

Headache in patients with pituitary adenoma: clinical and paraclinical findings.

AIM: The aim of this article is to generate hypotheses for the mechanism of pituitary adenoma headache. PATIENTS AND METHODS: Fifty-eight patients with pituitary adenoma were prospectively analysed for prevalence and manifestation of tumour headache. Intrapersonal and neoplasm-associated risk factors were assessed. RESULTS: Twenty-four patients (41%) had tumour-attributed headache, seven had migraine-like, 11 tension-type headache-like headache, and three both. Cluster headache-like headache was found once, and two headaches remained unclassified. Tumour-attributed headache was associated with a positive history of headache (p = 0.03; OR 3.4), nicotine abuse (p < 0.01; OR 4.7), intake of acute headache medication (p = 0.04; OR 3.3), and a higher tumour proliferation indicated by a Ki67-labelling index (LI) >3% (p = 0.02; OR 11.0). For patients with migraine-like tumour-attributed headache, risk factors were younger age (p = 0.02), nicotine abuse (p < 0.01; OR 10.9), acute headache treatment (p < 0.01; OR 9.0), and Ki67-LI >3% (p = 0.03; OR 14.1). For tension-type headache-like headache, the main risk factor was a positive history of tension-type headache (p = 0.045; OR 5.6). CONCLUSION: Headache predisposition and local tumour effects might be important for the pathophysiology of pituitary adenoma headache and tumour headache in general.

P2X7 receptor blockade reverses purinergic facilitation of neck muscle nociception in mice.

INTRODUCTION: Facilitation of neck muscle nociception mediated via purinergic signalling may play a role in the pathophysiology of tension-type headache (TTH). The present study addressed reversal of purinergic facilitation of brainstem nociception via P2X7 antagonist action in anaesthetized mice. METHODS: Following administration of α,ß-meATP (i.m. 20 µL/min, 20 µL each) into semispinal neck muscles, the impact of neck muscle nociceptive input on brainstem processing was monitored by the jaw-opening reflex in anaesthetized mice (n = 20). The hypothesized involvement of the P2X7 receptor in the α,ß-meATP effect was addressed with i.p. (systemic) and i.m. (semispinalis, 20 µL/min, 20 µL each) administration of P2X7 inhibitor A438079 during established facilitation; i.p. saline served as control. RESULTS: α,ß-meATP reliably induced jaw-opening reflex facilitation (256 ± 48% (mean ± SEM), n = 20). I.p. A438079 (150, 300 µmol/kg) completely reversed this α,ß-meATP effect dose-dependently. Neither saline nor intramuscular A438079 (100 µM) altered facilitated brainstem nociceptive processing. DISCUSSION: These data suggest that muscular structures are not directly involved in the P2X7 antagonist-mediated reversal of purinergic facilitation. Instead, involvement of neuronal structures, particularly of the central nervous system, seems more probable. The results from this animal experimental model may point to involvement of purinergic P2X7 receptors in TTH pathophysiology and may suggest potential future targets for its pharmacological treatment.

Acetylsalicylic acid inhibits α,ß-meATP-induced facilitation of neck muscle nociception in mice--implications for acute treatment of tension-type headache.

Infusion of α,ß-methylene ATP (α,ß-meATP) into murine neck muscle facilitates brainstem nociception. This animal experimental model is suggested to be appropriate for investigating pathophysiological mechanisms in tension-type headache. It was hypothesized that d-lysine acetylsalicylic acid (ASA, aspirin®) reverses this α,ß-meATP effect. Facilitation of neck muscle nociceptive processing was induced via bilateral infusion of α,ß-meATP into semispinal neck muscles (100 nM, 20 µl each) in 42 anesthetized mice. Brainstem nociception was monitored by the jaw-opening reflex elicited via electrical tongue stimulation. The hypothesis was addressed by subsequent (15, 30, 60 mg/kg) and preceding (60 mg/kg) intraperitoneal ASA injection. Saline served as control to ASA solution. Subsequent ASA dose-dependently reversed α,ß-meATP-induced reflex facilitation and was the most prominent with 60 mg/kg. Preceding 60 mg/kg ASA prevented reflex facilitation. Cyclooxygenases are involved in nociceptive transmission. Former experiments showed that unspecific inhibition of cyclooxygenases does not alter the α,ß-meATP effect. This suggests a specific mode of action of ASA. The concept is accepted that neck muscle nociception is involved in the pathophysiology of tension-type headache. Thus, objective proof of ASA effects in this experimental model may emphasize its major role in pharmacological treatment of tension-type headache attacks.

Inhibition of nNOS prevents and inhibition of iNOS reverses α,ß-meATP-induced facilitation of neck muscle nociception in mice.

Infusion of α,ß-methylene ATP (α,ß-meATP) into murine neck muscle facilitates brainstem nociception. Unspecific nitric oxide synthase (NOS) inhibition prevents and reverses this sensitization. It is unclear whether neuronal (nNOS), inducible (iNOS) or endothelial NOS isoenzymes are involved in this α,ß-meATP effect. Hypothesized involvement of nNOS isoenzyme was addressed by preceding (0.5, 1, and 2 mg/kg) and subsequent (2 mg/kg) intraperitoneal injection of the nNOS-inhibitor NPLA. iNOS involvement was addressed by subsequent, intraperitoneal administration of the iNOS-inhibitor 1400 W (2 mg/kg). Brainstem nociception was monitored by the jaw-opening reflex elicited via electrical tongue stimulation in 45 anesthetized mice. Preceding NPLA dose-dependently prevented α,ß-meATP-induced reflex facilitation. Whereas subsequent inhibition of nNOS showed no effect, iNOS inhibition by 1400 W significantly reversed reflex facilitation. Data provide evidence that nNOS plays a major role in induction and iNOS in maintenance of facilitation in neck muscle nociception. Divergent roles of NOS isoenzymes may promote research on target specific treatment for headache and neck muscle pain.

Pathophysiology of fibromyalgia: a comparison with the tension-type headache, a localized pain syndrome.

Fibromyalgia (FM) is thought to occur because of the combination of interactions among neurotransmitters, such as neuropeptide Y (NPY), stressors, hormones, cytokines, and both the immune and sympathetic nervous systems. The aim of this study was to evaluate serum concentrations of cytokines, antipolymer antibodies (APA), and NPY in 51 patients with FM, 25 with tension-type headache (TTH), and 15 healthy controls. Serum concentrations of eight different cytokines, APA and NPY, were measured. Interleukin (IL)-1RA, IL-6, IL-10, and tumor necrosis factor-alpha were higher in serum of FM patients compared with TTH patients and a significant correlation between IL-10 and Fibromyalgia Impact Questionnaire score was observed. There was a significant difference between FM and TTH versus controls in NPY levels, but not in APA levels. Cytokines and NPY take part in pain modulation and even if they are altered in FM they cannot be considered as measurable biomarkers of disease.

Chronic tension-type headache with vitamin D deficiency: casual or causal association?

The prevalence of tension-type headache and vitamin D deficiency are both very high in the general population. The inter-relations between the two have not been explored in the literature. We report 8 patients with chronic tension-type headache and vitamin D deficiency (osteomalacia). All the patients responded poorly to conventional therapy for tension headache. The headache and osteomalacia of each of the 8 patients responded to vitamin D and calcium supplementation. The improvement in the headache was much earlier than the improvements in the symptom complex of osteomalacia. We also speculate on the possible mechanisms for headache in the patients with vitamin D deficiency.

Chronic tension-type headache: what is new?

PURPOSE OF REVIEW: This review discusses current data on nosological boundaries related to diagnosis, pathophysiology and therapeutic strategies in chronic tension-type headache (CTTH). RECENT FINDINGS: Diagnostic criteria of CTTH should be adapted to improve its sensitivity against migraine. It seems that mechanical pain sensitivity is a consequence and not a causative factor of CTTH. Recent evidence is modifying previous knowledge about relationships between muscle tissues and CTTH, suggesting a potential role of muscle trigger points in the genesis of pain. An updated pain model suggests that headache perception can be explained by referred pain from trigger points in the craniocervical muscles, mediated through the spinal cord and the trigeminal nucleus caudalis rather than only tenderness of the muscles themselves. Different therapeutic strategies, pharmacological, physical therapy, psychological and acupuncture, are generally used. The therapeutic efficacy of nonsteroidal anti-inflammatory drugs remains incomplete. The tricyclic antidepressants are the most used first-line therapeutic agents for CTTH. Surprisingly, few controlled studies have been performed and not all of them have found an efficacy superior to placebo. Further, there is insufficient evidence to support/refute the efficacy of physical therapy in CTTH. SUMMARY: Although there is an increasing scientific interest in CTTH, future studies incorporating subgroups of patients who will likely to benefit from a specific treatment (clinical prediction rules) should be conducted.

Excitatory and inhibitory purinergic control of neck muscle nociception in anaesthetized mice.

Tension-type headache is associated with noxious input from neck muscles. Due to the importance of purinergic mechanisms in muscle nociception, experimental studies typically inject alpha,beta-methyleneadenosine 5'-triphosphate (alpha,beta-meATP). In contrast to native adenosine 5'-triphosphate (ATP), alpha,beta-meATP has a narrow receptor profile and remains stable in tissue. The present study administered alpha,beta-meATP or ATP in semi-spinal neck muscles in anaesthetized mice (n = 65) in order to address different effects in neck muscle nociception. The jaw-opening reflex monitored the impact of neck muscle noxious input on brainstem processing. Injection of alpha,beta-meATP induced reflex facilitation in a dose-dependent manner. In contrast, only the lowest ATP dosage evoked facilitation. Preceding P2Y(1) receptor blockade revealed facilitation even under high-dosage ATP. Ongoing facilitation after alpha,beta-meATP injection neutralized under subsequent activation of P2Y(1) receptors. Results demonstrate opposing excitatory P2X and inhibitory P2Y effects of ATP in neck muscle nociception. These mechanisms may be involved in the pathophysiology of neck muscle pain in man.

Bilateral transverse sinus stenosis and idiopathic intracranial hypertension without papilledema in chronic tension-type headache.

Previous MR studies have established that bilateral transverse sinus stenosis (BTSS) predicts idiopathic intracranial hypertension without papilledema (IIHWOP) in migraine. However, it is uncertain whether BTSS identifies IIHWOP in patients with chronic tension-type headache (CTTH): using cerebral MR venography this study aimed to address this question.In a prospective study from February 2002 to December 2006, 198 consecutive patients with CTTH underwent MR venography. Of these patients, 58 underwent lumbar puncture to measure cerebrospinal fluid (CSF) pressure. MR venography and lumbar puncture were also performed in 45 age-matched control subjects. BTSS was considered present when the signal flow was poor or lacking (flow gap) in the mid-lateral portion of both transverse sinuses. IIHWOP was diagnosed if the patient met the diagnostic criteria for idiopathic intracranial hypertension and did not have papilledema. Among the 198 patients with CTTH who underwent MR venography, 18 (9%) had BTSS. Thirteen of these 18 patients with BTSS underwent lumbar puncture, and nine (69.2%) had IIHWOP. CSF opening pressure was normal in all 45 patients as well as in all 45 controls with normal MR venography.These data suggest that BTSS on MR venography is associated with increased intracranial pressure in the absence of papilledema in patients with headache mimicking CTTH.