The aim of the present thesis was to investigate the pathophysiology of chronic tension-type headache with special reference to central mechanisms. Increased tenderness to palpation of pericranial myofascial tissues is the most apparent abnormality in patients with tension-type headache. A new piece of equipment, a so-called palpometer, that makes it possible to control the pressure intensity exerted during palpation, was developed. Thereafter, it was demonstrated that the measurement of tenderness could be compared between two observers if the palpation pressure was controlled, and that the Total Tenderness Scoring system was well suited for the scoring of tenderness during manual palpation. Subsequently, it was found that pressure pain detection and tolerance thresholds were significantly decreased in the finger and tended to be decreased in the temporal region in chronic tension-type headache patients compared with controls. In addition, the electrical pain threshold in the cephalic region was significantly decreased in patients. It was concluded that the central pain sensitivity was increased in the patients probably due to sensitization of supraspinal neurones. The stimulus-response function for palpation pressure vs. pain was found to be qualitatively altered in chronic tension-type headache patients compared with controls. The abnormality was related to the degree of tenderness and not to the diagnosis of tension-type headache. In support of this, the stimulus-response function was found to be qualitatively altered also in patients with fibromyalgia. It was concluded that the qualitatively altered nociception was probably due to central sensitization at the level of the spinal dorsal horn/trigeminal nucleus. Thereafter, the prophylactic effect of amitriptyline, a non-selective serotonin (5-HT) reuptake inhibitor, and of citalopram, a highly selective 5-HT reuptake inhibitor, was examined in patients with chronic tension-type headache. Amitriptyline reduced headache significantly more than placebo, while citalopram had only a slight and insignificant effect. It was concluded that the blockade of 5-HT reuptake could only partly explain the efficacy of amitriptyline in tension-type headache, and that also other actions of amitriptyline, e.g. reduction of central sensitization, were involved. Finally, the plasma 5-HT level, the platelet 5-HT level and the number of platelet 5-HT transporters were found to be normal in chronic tension-type headache. On the basis of the present and previous studies, a pathophysiological model for tension-type headache is presented. According to the model, the main problem in chronic tension-type headache is central sensitization at the level of the spinal dorsal horn/trigeminal nucleus due to prolonged nociceptive inputs from pericranial myofascial tissues. The increased nociceptive input to supraspinal structures may in turn result in supraspinal sensitization. The central neuroplastic changes may affect the regulation of peripheral mechanisms and thereby lead to, for example, ...

Background and purpose Trigeminal neuralgia (TN) is an extremely painful condition which can be difficult to diagnose and treat. In Europe, TN patients are managed by many different specialities. Therefore, there is a great need for comprehensive European guidelines for the management of TN. The European Academy of Neurology asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with TN. Methods A systematic review of the literature was performed and recommendations was developed based on GRADE, where feasible; if not, a good practice statement was given. Results The use of the most recent classification system is recommended, which diagnoses TN as primary TN, either classical or idiopathic depending on the degree of neurovascular contact, or as secondary TN caused by pathology other than neurovascular contact. Magnetic resonance imaging (MRI), using a combination of three high‐resolution sequences, should be performed as part of the work‐up in TN patients, because no clinical characteristics can exclude secondary TN. If MRI is not possible, trigeminal reflexes can be used. Neurovascular contact plays an important role in primary TN, but demonstration of a neurovascular contact should not be used to confirm the diagnosis of TN. Rather, it may help to decide if and when a patient should be referred for microvascular decompression. In acute exacerbations of pain, intravenous infusion of fosphenytoin or lidocaine can be used. For long‐term treatment, carbamazepine or oxcarbazepine are recommended as drugs of first choice. Lamotrigine, gabapentin, botulinum toxin type A, pregabalin, baclofen and phenytoin may be used either alone or as add‐on therapy. It is recommended that patients should be offered surgery if pain is not sufficiently controlled medically or if medical treatment is poorly tolerated. Microvascular decompression is recommended as first‐line surgery in patients with classical TN. No recommendation can be given for choice between any neuroablative treatments or between them and microvascular decompression in patients with idiopathic TN. Neuroablative treatments should be the preferred choice if MRI does not demonstrate any neurovascular contact. Treatment for patients with secondary TN should in general follow the same principles as for primary TN. In addition to medical and surgical management, it is recommended that patients are offered psychological and nursing support. Conclusions Compared with previous TN guidelines, there are important changes regarding diagnosis and imaging. These allow better characterization of patients and help in decision making regarding the planning of medical and surgical management. Recommendations on pharmacological and surgical management have been updated. There is a great need for future research on all aspects of TN, including pathophysiology and management.

Background and aimMonoclonal antibodies acting on the calcitonin gene-related peptide or on its receptor are new drugs to prevent migraine. Four monoclonal antibodies have been developed: one targeting the calcitonin gene-related peptide receptor (erenumab) and three targeting the calcitonin gene-related peptide (eptinezumab, fremanezumab, and galcanezumab). The aim of this document by the European Headache Federation (EHF) is to provide an evidence-based and expert-based guideline on the use of the monoclonal antibodies acting on the calcitonin gene-related peptide for migraine prevention.MethodsThe guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic review and analysis of the literature, assessed the quality of available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided.ResultsWe found low to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in patients with episodic migraine and medium to high quality of evidence to recommend erenumab, fremanezumab, and galcanezumab in patients with chronic migraine. For several clinical questions, there was not enough evidence to provide recommendations using the GRADE approach and recommendations relied on experts’ opinion.ConclusionMonoclonal antibodies acting on the calcitonin gene-related peptide are new drugs which can be recommended for migraine prevention. Real life data will be useful to improve the use of those drugs in clinical practice.

Introduction Trigeminal neuralgia (TN) is characterized by touch-evoked unilateral brief shock-like paroxysmal pain in one or more divisions of the trigeminal nerve. In addition to the paroxysmal pain, some patients also have continuous pain. TN is divided into classical TN (CTN) and secondary TN (STN). Etiology and pathophysiology Demyelination of primary sensory trigeminal afferents in the root entry zone is the predominant pathophysiological mechanism. Most likely, demyelination paves the way for generation of ectopic impulses and ephaptic crosstalk. In a significant proportion of the patients, the demyelination is caused by a neurovascular conflict with morphological changes such as compression of the trigeminal root. However, there are also other unknown etiological factors, as only half of the CTN patients have morphological changes. STN is caused by multiple sclerosis or a space-occupying lesion affecting the trigeminal nerve. Differential diagnosis and treatment Important differential diagnoses include trigeminal autonomic cephalalgias, posttraumatic or postherpetic pain and other facial pains. First line treatment is prophylactic medication with sodium channel blockers, and second line treatment is neurosurgical intervention. Future perspectives Future studies should focus on genetics, unexplored etiological factors, sensory function, the neurosurgical outcome and complications, combination and neuromodulation treatment as well as development of new drugs with better tolerability.

Background: Tension-type headache (TTH) is the most prevalent headache type and is causing a high degree of disability. Treatment of frequent TTH is often difficult. Objectives: To give evidence-based or expert recommendations for the different treatment procedures in TTH based on a literature search and the consensus of an expert panel. Methods: All available medical reference systems were screened for the range of clinical studies on TTH. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A, B or C recommendations and good practice points. Recommendations: Non-drug management should always be considered although the scientific basis is limited. Information, reassurance and identification of trigger factors may be rewarding. Electromyography (EMG) biofeedback has a documented effect in TTH, whilst cognitive-behavioural therapy and relaxation training most likely are effective. Physical therapy and acupuncture may be valuable options for patients with frequent TTH, but there is no robust scientific evidence for efficacy. Simple analgesics and non-steroidal anti-inflammatory drugs are recommended for the treatment of episodic TTH. Combination analgesics containing caffeine are drugs of second choice. Triptans, muscle relaxants and opioids should not be used. It is crucial to avoid frequent and excessive use of analgesics to prevent the development of medicationoveruse headache. The tricyclic antidepressant amitriptyline is drug of first choice for the prophylactic treatment of chronic TTH. Mirtazapine and venlafaxine are drugs of second choice. The efficacy of the prophylactic drugs is often limited, and treatment may be hampered by side effects. ObjectivesThese guidelines aim to give evidence-based recommendations for the acute and prophylactic drug treatment of TTH. In addition, the guidelines aim to provide a short overview on non-drug treatment of TTH based on the best performed controlled trials, reviews and meta-analyses, whilst the vast amount of uncontrolled reports of non-drug treatment will not be considered. A brief clinical description of the headache disorders is included. The definitions follow the diagnostic criteria of the International Headache Society (IHS) [1].

Objective.-To prospectively describe the clinical characteristics of classical trigeminal neuralgia (TN) in a standardized manner.Background.-TN is a rare disease and most clinicians only see a few patients. There is a lack of prospective systematic studies of the clinical characteristics of TN. We hypothesized that contrary to current thinking, some TN patients suffer from sensory abnormalities at neurological examination.Methods.-Clinical characteristics such as demographics, pain characteristics, and comorbidities were systematically and prospectively collected from consecutive TN patients in a tertiary referral center in a cross-sectional study.Results.-A total of 158 patients were included. Average age of onset was 52.9 years. TN was more prevalent in women (95; 60%) than in men (63; 40%), P = .011, and more often located on the right (89; 56%) than on the left side (64; 41%), P = .043. It affected solely the second and/or third trigeminal branch in 109 (69%) while the first branch alone was affected in only 7 (4%). Notably, 78 (49%) had concomitant persistent pain in addition to paroxysmal stabbing pain. Autonomic symptoms were present in 48 (31%). Patients who had not undergone surgery for TN had sensory abnormalities in 35 (29%).Conclusions.-This, the first study in a series of papers focusing on the clinical, radiological, and etiological aspects of TN, revealed that the symptomatology of TN includes a high percentage of concomitant persistent pain, autonomic symptoms, and sensory abnormalities. These findings offer new insights to the prevailing clinical impression of the clinical characteristics in TN.

Objectives-Although the tricyclic antidepressant amitriptyline is extensively used in the prophylactic treatment of chronic tension-type headache, only few studies have investigated the efficacy of this treatment and the results are contradictory. In addition, the new selective serotonin reuptake inhibiting antidepressants, which are widely used in depression and of potential value in pain management, have never been investigated in a placebo controlled study of tension-type headache. The aim was to evaluate the efficacy of amitriptyline and of the selective serotonin reuptake inhibitor citalopram in chronic tensiontype headache. Methods-Forty non-depressed patients with chronic tension type headache were included in a 32 week, double blind, placebo controlled, threeway crossover study. Results-Thirty four patients completed the trial. Amitriptyline reduced area under the headache curve by 30% compared with placebo (P = 0.002), whereas citalopram had no significant effect (P = 0.68). Explanatory analyses showed that amitriptyline significantly reduced the duration of headache (P = 0.01), headache frequency (P = 0.01), and intake of analgesics (P = 0.02) but not headache intensity (P = 0.12). Conclusion-Although amitriptyline did not eliminate the headache, it provided a clinically important reduction of headache in the majority of otherwise treatment resistant patients. The differential effect of amitriptyline and citalopram indicates that mechanisms other than inhibition of serotonin reuptake are involved in the analgesic effect of the tricyclic antidepressants. Amitriptyline, but not citalopram, is valuable in the prophylactic treatment of chronic tension type headache. (7 Neurol Neurosurg Psychiatry 1996;61:285-290)

The present finding of a general hypersensitivity to pain stimuli in chronic tension-type headache indicates that central factors play an important role in the pathogenesis of this disorder.