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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., (© 2024. The Author(s).)

Hyperprolactinemia is a condition characterised by an increase of prolactin blood levels (more than 100-200 ng/ml). It is the most common endocrine disorder of the hypothalamic-pituitary axis. The clinical characteristics of the headache-hyperprolactinemia-hypophyseal-adenoma association are discussed, the various diagnostic and treatment possibilities are explored and the etiology of the headache is considered in the light of several pathogenetic possibilities. We present two cases. (1) A 35-year-old woman suffering from chronic tension-type headache interspersed with occasional episodes of migraine without aura (as defined by the International Headache Society criteria). She had also suffered menstrual cycle alterations since the age of 16. At the age of 30 she developed amenorrhea with hyperprolactinemia. Computed tomography (CT) and magnetic resonance imaging (MRI) scans revealed a median-left intrasellar mass. Treatment with cabergoline resulted in complete resolution of both types of headache and the menstrual cycle and prolactin levels returned to normal. The therapy also reduced the volume of the tumour. (2) The second case relates to a 47-year-old man who had been suffering from tension-type headaches for almost 3 months. The patient had never previously suffered from headaches. CT and MRI scans showed a large sellar and suprasellar lesion with raised serum prolactin levels. Treatment with cabergoline had significantly reduced the prolactin levels and had also improved the patient's headaches. High-resolution CT, with and without contrast, or MRI is necessary to visualise microprolactinomas (and other sellar lesions) and confirm the diagnosis.

The term nocebo refers to a harmful, unpleasant or undesirable adverse event a subject manifests after receiving an inert dummy drug or placebo. This reaction is originating by the patients fear and negative expectation that medical treatment most likely will produce unfavorable consequences instead of healing. Like placebo, nocebo shares key functions in pain conditions. Two recent systemic meta-analyses searched for nocebo in trials for prevention of migraine and tension-type headache and revealed that 1 out of 20 patients treated with placebo withdraw treatment due to adverse effects. Additionally, adverse events in placebo groups mirrored the adverse events expected of the active medication studied, confirming that pretrial suggestions induce the adverse events in placebo-treated patients. Therefore, nocebo reduces the study population by 10% and limits the treatment outcomes in randomized controlled trials for primary headaches. The potential implications of this substantial nocebo effect for both trial designing and clinical practice are discussed in this article.

The tenderness of pericranial myofascial tissues and number of myofascial trigger points are considerably increased in patients with tension-type headache (TTH). Mechanisms responsible for the increased myofascial pain sensitivity have been studied extensively. Peripheral activation or sensitization of myofascial nociceptors could play a role in causing increased pain sensitivity, but firm evidence for a peripheral abnormality still is lacking. Peripheral mechanisms are most likely of major importance in episodic TTH. Sensitization of pain pathways in the central nervous system due to prolonged nociceptive stimuli from pericranial myofascial tissues seem to be responsible for the conversion of episodic to chronic TTH. Treatment directed toward muscular factors include electromyography biofeedback, which has a documented effect in patients with TTH, as well as physiotherapy and muscle relaxation therapy, which are most likely effective. Future studies should aim to identify the source of peripheral nociception.

Tension-type headache is the most common headache type worldwide. Chronic tension-type headache (CTTH) affects 2% to 3% of patients, yet it represents the least talked about subtype of chronic daily headache. There is much debate in the headache community on whether CTTH exists as its own entity or is a milder form of chronic migraine (CM), because there are similarities and differences between the two headache forms. This article reviews CTTH, as well as the current pathophysiology and treatment, and discusses controversial issues in the diagnosis of CTTH and CM.

Tension-type headache (TTH) is the most prevalent primary headache disorder. An important factor in the long-term prognosis of TTH is the overuse of acute medications used to treat headache. There are many reasons why patients with TTH overuse acute medications, including biobehavioral influences, dependency, and a lack of patient education. Chronic daily headache occurs in 4.1% of the general population, and chronic tension-type headache and medication overuse headache (MOH) occur in approximately 2.2% and 1.5%, respectively. A proper diagnosis is essential for the treatment of these patients. Treatment should include pathological considerations concerning TTH and MOH, which include peripheral and central mechanisms. Because TTH with MOH carries the worst prognosis, more clinical studies focusing on the complex interaction and treatments of TTH and MOH are needed.

Tension-type headache (TTH) is the most prevalent form of primary headache in the general population. We discuss advances in the treatment of TTH. We briefly review nonpharmacologic therapies and then focus on current pharmacologic strategies. For acute treatment, the most common interventions involve the use of simple analgesics and anti-inflammatory medications, often taken by the patient without a prescription. For preventive treatment, amitriptyline is the best-studied drug, but nortriptyline, mirtazapine, tizanidine, the selective serotonin reuptake inhibitors, and other medications can be used. We close by discussing potential future therapies, including calcitonin gene-related peptide receptor antagonism, as well as substance P and the nitric oxide pathways.

The therapy for tension-type headache remains insufficient, and recent advances have been scarce. Although tricyclic antidepressants are at the forefront of treatment advances, upcoming agents tentatively modifying central sensitization are promising. Botulinum toxin failed to meet expectations. This article reviews current treatments, emphasizing newer approaches. Much remains to be achieved.

Tension-type headache, the most common type of primary headache disorder, is reclassified in the second International Headache Society classification with clear diagnostic criteria. Chronic tension-type headache (CTTH) differs from episodic form in frequency, lack of response to most treatment strategies, more medication overuse, and more loss of quality of life. New concepts in the pathophysiology of CTTH emphasize the possible role of central nociceptive pathway sensitization in addition to peripheral myogenic factors. Mechanisms of central sensitization, even though poorly understood, may involve nitric oxide system and N-methyl-D-aspartate receptors. Future treatment modalities are likely to be based on such mechanisms. Using MRI and voxel-based morphometry, structural abnormalities have been found in patients with CTTH for the first time. Pain processing areas such as dorsal rostral and ventral pons, anterior cingulate cortex, anterior and posterior insular cortex, right posterior temporal lobe, orbitofrontal cortex, para hippocampus bilaterally, and the right cerebellum were found to have decreased gray matter in patients with CTTH compared with control subjects and patients with medication overuse headache. Amitriptyline remains the most effective preventive treatment so far. The role of botulinum toxin is not fully defined.

Behavioral treatments (relaxation, biofeedback, cognitive-behavioral therapy) have been empirically validated for migraine and tension-type headaches, with recent meta-analyses yielding 37% to 50% reductions in tension-type headache, comparing favorably with 33% reduction from medication prophylaxis (amitriptyline). Research has moved toward increasing availability and cost effectiveness through alternative delivery formats and combining and comparing them with standard medications. Further modifications would make standard behavioral treatments available and conducive to primary care settings where most patients receive treatment. Beyond the current behavioral and drug treatments, we propose a fundamental shift in conceptualization and treatment for headache.

Tension-type headache is a common primary headache with tremendous socioeconomic impact. Establishment of an accurate diagnosis is important before initiation of any pharmacologic therapy. Simple analgesics and nonsteroidal anti-inflammatory drugs are the mainstays of treatment of episodic tension-type headache. The tricyclic antidepressant amitriptyline is the drug of choice in the preventive treatment of chronic tension-type headache. Progress in basic neuroscience has emphasized the importance of nitric oxide inhibition and N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid receptor antagonism in the treatment of chronic pain. It has been demonstrated that inhibition of nitric oxide is effective in chronic tension-type headache. These interesting data indicate that more specific and effective treatment possibilities will emerge in the future.

The first International Headache Society classification defined tension-type headaches by itemizing characteristics of migraines that tension-type headaches did not possess. As a result, tension-type headaches (episodic and chronic) remain the most nonspecific of all the commonly observed primary headaches. Until recently, there has been little impetus on the part of the pharmaceutical industry to investigate tension-type headaches; many of the potentially useful drugs are now generic and unprofitable. In addition, few investigators have pursued the study of tension-type headache because of its more glamorous neighbor, migraine. As a result, there are few well-designed studies on the pharmacotherapy of tension-type headaches. The few studies that exist support the use of age-old standard drug classes, the tricyclic antidepressants and the nonsteroidal anti-inflammatory drugs. New research is emerging that points to the potential use of botulinum toxin and nitric synthase inhibitors. More scientifically rigorous clinical studies are needed.

Butalbital compounds are of proven efficacy in the treatment of tension headache. Decades of experience have established their value in the treatment of other mild-to-moderate headaches. Untold numbers of people rely on these medications as their drug of choice or use them when vasoconstrictors, opioids, or nonsteroidal anti-inflammatory agents are contraindicated. The medications are cost-effective with only occasional and minor immediate adverse effects. Their overuse may cause the evolution of episodic primary headaches to chronic daily headaches; however, removal of these agents from the market would reduce the chronic daily headache in the general population by a small fraction of 1%.

In the United States analgesic-overuse headache is often caused by butalbital-containing analgesics. These agents can cause physical and psychological dependency, and dangerous withdrawal syndromes. Butalbital-containing analgesics have already been banned in several European countries. They are proven effective in tension-type headache, but not in migraine; there are many alternative treatments for migraine and tension-type headache. In the 20 years since analgesic overuse headache was widely recognized, butalbital overuse has remained distressingly common. It is time to ban these agents.

Simple analgesics such as ibuprofen, aspirin, and acetaminophen have long been used in the treatment of tension-type headache. Studies of combination agents of aspirin with caffeine or acetaminophen with caffeine have also demonstrated efficacy as analgesic agents. Other evidence also suggests that caffeine may have an analgesic effect unto itself in the relief of pain. We undertook the direction of a multicenter, double-blind, placebo-controlled, parallel trial to assess the efficacy and safety of ibuprofen combined with caffeine in the treatment of tension-type headache. The study was designed to also verify the analgesic efficacy of caffeine and further assess the role of tension-type headache as a model for the study of pain.

Migraine and tension-type headaches are two of the most common types of primary headache disorders in children. Migraine is a primary central nervous system disorder characterized by triggered or spontaneous episodes of activation of trigemino-vascular complex, neurogenic inflammation around vessels and meninges, and stimulation of the peripheral and central pain pathways of the trigemino-cervical complex. The triptans, by their selective agonistic action on 5-HT1B/1D receptors, are very effective in the treatment of migraine pain and associated symptoms. Early studies on the safety and efficacy of triptans in the management of childhood migraine show encouraging results. We propose a stratified-care model for the management of migraine in children, and discuss pharmacotherapy based on the pathophysiologic mechanisms of migraine pain. Management of tension-type headaches requires comprehensive medical and psychologic evaluation and an individualized approach for a successful outcome.