Cluster Headache Pathophysiology—A Disorder of Network Excitability?

Patients’ accounts of cluster headache attacks, ictal restlessness, and electrophysiological studies suggest that the pathophysiology involves Aδ-fibre nociceptors and the network processing their input. Continuous activity of the trigeminal autonomic reflex throughout the in-bout period results in central sensitization of these networks in many patients. It is likely that several factors force circadian rhythmicity upon the disease. In addition to sensitization, circadian changes in pain perception and autonomic innervation might influence the excitability of the trigeminal cervical complex. Summation of several factors influencing pain perception might render neurons vulnerable to spontaneous depolarization, particularly at the beginning of rapid drops of the pain threshold (“summation headache”). In light of studies suggesting an impairment of short-term synaptic plasticity in CH patients, we suggest that the physiologic basis of CH attacks might be network overactivity—similarly to epileptic seizures. Case reports documenting cluster-like attacks support the idea of distinct factors being transiently able to induce attacks and being relevant in the pathophysiology of the disorder. A sustained and recurring proneness to attacks likely requires changes in the activity of other structures among which the hypothalamus is the most probable candidate.

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Pain processing in Schizophrenia

European Psychiatry ◽

10.1016/s0924-9338(11)73833-0 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 2130-2130

Author(s):

O. Bonnot ◽

S. Tordjman

Keyword(s):

Clinical Studies ◽

Pain Sensitivity ◽

Pain Threshold ◽

Pain Perception ◽

Psychiatric Patients ◽

Case Reports ◽

Experimental Studies ◽

Self Report ◽

Pain Expression ◽

Endogenous Analgesia

We will propose a critical review of the scientific literature regarding pain and schizophrenia, examine the empirical basis for the reported pain insensitivity of schizophrenia, and emphasize the distinction between behavioral responses to pain or self-reported pain and physiological response to painful stimuli. Litterature is scarse and could be classified in 4 groups: case reports (n = 9), clinical studies (n = 23), experimental research (n = 20) and review articles (n = 5).The analysis of Case reports and clinical studies show reduced pain reactivity in patients with schizophrenia compared to healthy controls or other psychiatric patients. In the same vein, experimental studies using self-report measures of pain reactivity generally reported higher pain perception thresholds in patients with schizophrenia. However, the only experimental study using a neurophysiological measure of pain reactivity (the nociceptive RIII reflex) demonstrated a normal pain threshold in schizophrenia.Review of clinical and experimental data indicates that in most situations behavioral pain reactivity and self-reported responses to pain are reduced in schizophrenia. However, there is little or no physiological evidence supporting pain insensitivity in schizophrenia. It can be suggested that the widely accepted notion of reduced pain sensitivity in schizophrenia is related more to a different mode of pain expression than to a real endogenous analgesia. We will also present preliminary data on pain sensitivity associating behavioural pain reactivity measurements, "objective" electrophysiological assessments and neurovegetative function recordings. Our results are in the line of the literature and strongly suggest that there is no analgesia in schizophrenia but a different mode of pain expression.

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Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache

Brain Sciences ◽

10.3390/brainsci10010030 ◽

2020 ◽

Vol 10 (1) ◽

pp. 30 ◽

Cited By ~ 5

Author(s):

Andrea Carmine Belin ◽

Caroline Ran ◽

Lars Edvinsson

Keyword(s):

Cluster Headache ◽

Pain Perception ◽

Primary Headache ◽

Active Phase ◽

Calcitonin Gene Related Peptide ◽

Primary Headaches ◽

Cgrp Receptor ◽

Related Peptide ◽

Calcitonin Gene ◽

Autonomic Reflex

Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP receptor complex have recently taken center stage as therapeutic targets for primary headaches, such as migraine. Multiple CGRP and CGRP receptor monoclonal antibodies, as well as small molecule antagonists (gepants) are on their way constituting a new frontier of migraine and possibly CH medication. During a CH attack, there is an activation of the trigeminal-autonomic reflex with the release of CGRP, and inversely if CGRP is administered to a CH patient in an active disease phase, it triggers an attack. Increased levels of CGRP have been found in ipsilateral jugular vein blood during the active phase of CH. This process is hypothesized to have a key role in the intense pain perception and in the associated distinctive vasodilation. So far, clinical tests of CGRP antibodies have been inconclusive in CH patients. This review summarizes the current state of knowledge on the role of CGRP in CH pathology, and as a target for future treatments.

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Reduction in Pain Sensitivity from Pharmacological Elevation of Blood Pressure in Persons with Chronically Low Blood Pressure

Journal of Psychophysiology ◽

10.1027/0269-8803.23.3.104 ◽

2009 ◽

Vol 23 (3) ◽

pp. 104-112 ◽

Cited By ~ 12

Author(s):

Stefan Duschek ◽

Heike Heiss ◽

Boriana Buechner ◽

Rainer Schandry

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Pain Sensitivity ◽

Pain Threshold ◽

Pain Perception ◽

Drug Effects ◽

Pressure Effects ◽

Double Blind ◽

Low Blood Pressure ◽

Present Trial

Recent studies have revealed evidence for increased pain sensitivity in individuals with chronically low blood pressure. The present trial explored whether pain sensitivity can be reduced by pharmacological elevation of blood pressure. Effects of the sympathomimetic midodrine on threshold and tolerance to heat pain were examined in 52 hypotensive persons (mean blood pressure 96/61 mmHg) based on a randomized, placebo-controlled, double-blind design. Heat stimuli were applied to the forearm via a contact thermode. Confounding of drug effects on pain perception with changes in skin temperature, temperature sensitivity, and mood were statistically controlled for. Compared to placebo, higher pain threshold and tolerance, increased blood pressure, as well as reduced heart rate were observed under the sympathomimetic condition. Increases in systolic blood pressure between points of measurement correlated positively with increases in pain threshold and tolerance, and decreases in heart rate were associated with increases in pain threshold. The findings underline the causal role of hypotension in the augmented pain sensitivity related to this condition. Pain reduction as a function of heart rate decrease suggests involvement of a baroreceptor-related mechanism in the pain attrition. The increased proneness of persons with chronic hypotension toward clinical pain is discussed.

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Short-term Change on Pressure Pain Threshold and Vertical Jump when Foam Roll Exercises and Vibration Foam Roll Exercises

Archives of Orthopedic and Sports Physical Therapy ◽

10.24332/aospt.2017.14.1.16 ◽

2018 ◽

Vol 14 (1) ◽

pp. 137-145

Author(s):

Sangwan Han

Keyword(s):

Pain Threshold ◽

Vertical Jump ◽

Pressure Pain Threshold ◽

Short Term ◽

Pressure Pain ◽

Short Term Change ◽

Term Change

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Can Residential Greenspace Exposure Improve Pain Experience? A Comparison between Physical Visit and Image Viewing

Healthcare ◽

10.3390/healthcare9070918 ◽

2021 ◽

Vol 9 (7) ◽

pp. 918

Author(s):

Hansen Li ◽

Xing Zhang ◽

Shilin Bi ◽

Yang Cao ◽

Guodong Zhang

Keyword(s):

Heart Rate ◽

State Anxiety ◽

Pain Threshold ◽

Pain Perception ◽

The State ◽

Subjective Stress ◽

Pain Experience ◽

Scenic Beauty ◽

Significant Difference ◽

Pain Stimuli

Reducing the burden of pain via greenspace exposure is a rising research topic. However, insufficient evidence has been found in relation to the environmental effect itself. Residential greenspace, as a convenient but limited natural environment for urban dwellers, has benefits and services yet to be discovered. Therefore, the current study recruited 24 young adults to evaluate the effects of physical visit to, or image viewing of, residential greenspace on pain perception and related psychophysiological outcomes, via simulated pain. Pain threshold and tolerance were recorded via the level of pain stimuli, and pain intensity was evaluated using the Visual Analog Scale (VAS). The state scale of the State–Trait Anxiety Inventory (STAI-S) and two adjective pairs were employed to measure the state anxiety and subjective stress, respectively. Meanwhile, heart rate (HR), heart rate variability (HRV), and blood pressure (BP) were measured to investigate physiological responses. Besides, Scenic Beauty Estimation (SBE) was also employed to assess participants’ preference regarding the experimental environments. The results revealed that visiting the greenspace significantly increased the pain threshold and tolerance, while no significant effect was observed for image viewing. On the other hand, no significant difference was observed in pain-related psychophysiological indices between the experimental settings, but significantly negative associations were found between the scores of SBE and subjective stress and state anxiety. In conclusion, the current study brings experimental evidence of improving pain experience via residential greenspace exposure, while the related psychophysiological benefits require further investigation.

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Pressure Algometry Evaluation of Two Occlusal Splint Designs in Bruxism Management-Randomized, Controlled Clinical Trial

Journal of Clinical Medicine ◽

10.3390/jcm10112342 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2342

Author(s):

Bartosz Dalewski ◽

Agata Kamińska ◽

Paweł Kiczmer ◽

Krzysztof Węgrzyn ◽

Łukasz Pałka ◽

...

Keyword(s):

Pain Threshold ◽

Pressure Pain Threshold ◽

Controlled Clinical Trial ◽

Randomized Controlled Clinical Trial ◽

Occlusal Splint ◽

Short Term ◽

Randomized Controlled ◽

Canine Guidance ◽

Medical University

The aim of this pilot study was to evaluate the short-term effectiveness of two different occlusal devices and their impact on the pressure pain threshold (PPT) values among patients who reported to the Dental Prosthetics Outpatient Clinic of Pomeranian Medical University (Szczecin, Poland) and who were diagnosed with probable bruxism. Two groups were formed (A and B) to which patients were assigned randomly. Each group used a different occlusal splint for bruxism management. The occlusal appliance by Okeson, or the bimaxillary splint, was used overnight by each patient for 30 days of the study. The PPT was measured twice, at the first visit and after 30 days of using each occlusal device, with Wagner Paintest FPX 25 algometer. Bruxism was diagnosed based on data from the patient’s medical history and from the physical examination. Nocturnal Bruxism Criteria according to the International Classification of Sleep Disorders (Third Edition) was used for the patient’s evaluation. Results: similar pain factor (PF) reduction was observed in both the examined groups, regardless of the device used; canine guidance and no guidance were similarly effective in terms of increasing pain resilience.

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Cluster headache in children and adolescents: a systematic review of case reports

Developmental Medicine & Child Neurology ◽

10.1111/dmcn.14923 ◽

2021 ◽

Author(s):

Sarah N M A N Bastos ◽

Bárbara L F Barbosa ◽

Sângela F Silva ◽

Ana G Krymchantowski ◽

Carla Jevoux ◽

...

Keyword(s):

Systematic Review ◽

Cluster Headache ◽

Children And Adolescents ◽

Case Reports

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Hypothalamic Activation in Trigeminal Autonomic Cephalgia: Functional Imaging of an Atypical Case

Cephalalgia ◽

10.1111/j.1468-2982.2004.00753.x ◽

2004 ◽

Vol 24 (9) ◽

pp. 753-757 ◽

Cited By ~ 46

Author(s):

T Sprenger ◽

M Valet ◽

M Hammes ◽

P Erhard ◽

A Berthele ◽

...

Keyword(s):

Cluster Headache ◽

Paroxysmal Hemicrania ◽

Cerebral Activation ◽

Atypical Case ◽

Clear Cut ◽

Oxygen Administration ◽

Autonomic Reflex ◽

Trigeminal Autonomic Cephalgia ◽

Hypothalamic Activation

We report headache induced BOLD changes in an atypical case of trigeminal autonomic cephalgia (TAC). A 68-year-old patient was imaged using fMRi during three attacks of a periorbital head-pain with a average duration of 3 min. During the attacks, left sided conjunctival injection, rhinorrhea, lacrimation, facial sweating and hypersalivation were apparent. These attacks were usually partly responsive to oxygen administration but otherwise refractory to any drug. The patient described either attacks with a duration of one minute or less or longer attacks persisting for maximum of 20 min with headaches occurring up to 100 times a day. When considering the symptoms, frequency, duration and therapeutic response of the patient's headache, no clear-cut classification to one of the subtypes of trigeminal autonomic cephalgias (cluster headache, paroxysmal hemicrania, SUNCT) or trigeminal neuralgia was possible. The cerebral activation pattern was similar but not identical to those previously observed in cluster headache and SUNCT with a prominent activation in the hypothalamic grey matter. This case study underlines the conceptual value of the term TAC for the group of headaches focusing around the trigeminal-autonomic reflex. Our results emphasize the importance of the hypothalamus as key region in the pathophysiology of this entity.

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