The role of androgens in migraine pathophysiology.

Migraine affects ∼12 % of the worldwide population and is more prevalent in females, which suggests a role of sex hormones in migraine pathophysiology. Most studies have focused on estrogen and progesterone, and the involvement of androgens has been less studied. However, due to the recent advances in androgen interventions, which could advance new androgen-based migraine treatments, it is critical to better understand the role of androgens in migraine.

Oral Delta-9-Tetrahydrocannabinol (THC) Increases Parasympathetic Activity and Supraspinal Conditioned Pain Modulation in Chronic Neuropathic Pain Male Patients: A Crossover, Double-Blind, Placebo-Controlled Trial.

Background: Disordered autonomic nervous system regulation and supraspinal pain inhibition have been repeatedly described in chronic pain. We aimed to explore the effects of δ-9-tetrahydrocannabinol (THC), an emerging treatment option, on autonomic nervous system and central pain modulation measures in patients with chronic pain.

Methods: Twelve male patients with chronic radicular neuropathic pain participated in a randomized, double-blind, crossover, placebo-controlled, single-administration trial.

How Sex Hormones Affect Migraine: An Interdisciplinary Preclinical Research Panel Review.

Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during puberty, pregnancy, and perimenopause. Ovarian steroids, such as estrogen and progesterone, exert complex effects on the peripheral and central nervous systems, including pain, a variety of special sensory and autonomic functions, and affective processing.

A developmental framework for understanding the influence of sex and gender on health: Pediatric pain as an exemplar.

Sex differences are a robust finding in many areas of adult health, including cardiovascular disease, psychiatric disorders, and chronic pain. However, many sex differences are not consistently observed until after the onset of puberty. This has led to the hypothesis that hormones are primary contributors to sex differences in health outcomes, largely ignoring the relative contributions of early developmental influences, emerging psychosocial factors, gender, and the interaction between these variables.

The brainstem's red nucleus was evolutionarily upgraded to support goal-directed action.

The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907).

Weak Relationships Between Psychological Factors and Experimental Pain Outcomes in Pain-Free Individuals: An Aggregate Analysis of 8 Studies.

Although psychological factors such as anxiety, depression, and pain catastrophizing are known to influence pain outcomes in chronic pain populations, there are mixed results regarding whether they influence experimental pain outcomes in pain-free individuals. The objectives of this study were to determine the associations between psychological factors and experimental pain outcomes in pain-free adolescents and adults. Relationships between anxiety, depression, and pain catastrophizing and experimental pain outcomes across 8 different studies (total N = 595) were examined in different populations of pain-free adult and adolescent participants.

Harnessing the conditioned pain modulation response in migraine diagnosis, outcome prediction, and treatment-A narrative review.

Objective: To present the potential use and relevance of the conditioned pain modulation (CPM) response to migraine diagnosis, outcome prediction, and treatment.

Background: The CPM response is a widely used laboratory test to examine inhibitory pain modulation capabilities.

Methods: This narrative review summarizes and synthesizes the findings on the CPM response in patients with migraine.

Communication of pain intensity and unpleasantness through magnitude ratings: Influence of scale type, but not gender of the participant.

Background: A critical aspect for most human pain research is the ability of participants to communicate their first-person, experiential perspective to a third-person observer. This communication is frequently accomplished via pain ratings. The scale type can influence the communication of pain experiences and can contribute to gender differences in pain.

Alterations in pain during adolescence and puberty.

During adolescence and puberty, alterations in pain, both experimental and clinical, are observed. In addition, adolescents undergo extensive biopsychosocial changes as they transition from childhood to adulthood. However, a better understanding of how the biopsychosocial changes during adolescence impact pain is needed to improve pain management and develop targeted pain interventions for adolescents.

Bridging the gap between preclinical scientists, clinical researchers, and clinicians: From animal research to clinical practice.

Background: Collaborations amongst researchers and clinicians with complementary areas of expertise enhance knowledge for everyone and can lead to new discoveries. To facilitate these interactions, shared language and a general understanding of how colleagues in different subfields of headache and headache research approach their work are needed.

Methods: This narrative review focuses on research methods applied in animal studies, human studies including clinical trials, and provides an overview of clinical practice.

Disentangling the roles of circadian rhythms and sleep drive in experimental pain sensitivity.

Differentiating between circadian rhythm and sleep's effect on pain is challenging, as these two systems can be tightly coupled. A recent study by Daguet et al. found that circadian rhythm, rather than sleep drive, significantly contributed to the variability of experimental heat pain sensitivity in humans.

Neural mechanisms underlying the conditioned pain modulation response: a narrative review of neuroimaging studies.

Processing spatially distributed nociceptive information is critical for survival. The conditioned pain modulation (CPM) response has become a common psychophysical test to examine pain modulation capabilities related to spatial filtering of nociceptive information. Neuroimaging studies have been conducted to elucidate the neural mechanisms underlying the CPM response in health and chronic pain states, yet their findings have not been critically reviewed and synthesized before.

To Calibrate or not to Calibrate? A Methodological Dilemma in Experimental Pain Research.

To calibrate or not to calibrate? This question is raised by almost everyone designing an experimental pain study with supra-threshold stimulation. The dilemma is whether to individualize stimulus intensity to the pain threshold / supra-threshold pain level of each participant or whether to provide the noxious stimulus at a fixed intensity so that everyone receives the identical input. Each approach has unique pros and cons which need to be considered to i) accurately design an experiment, ii) enhance statistical inference in the given data and, iii) reduce bias and the influence of confounding factors in the individual study e.

Amygdalar functional connectivity during resting and evoked pain in youth with functional abdominal pain disorders.

Pediatric functional abdominal pain disorders (FAPD) are highly prevalent, difficult to diagnose, and challenging to treat. The brain systems supporting FAPD remain poorly understood. This investigation examined the neuromechanisms of FAPD during a well-tolerated visceral pain induction task, the water load symptom provocation task (WL-SPT).

New insight into the neural mechanisms of migraine in adolescents: Relationships with sleep.

Objective: This case-control study examines if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents.

Background: Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Sleep is often disturbed in adolescents with migraine, and could contribute to the alterations in functional connectivity.

Pain sensitivity does not differ between obese and healthy weight individuals.

Introduction: There is emerging evidence suggesting a relationship between obesity and chronic pain.

Objectives: The aim of this study was to determine whether pain-free obese individuals display altered pain responses to acute noxious stimuli, thus raising the possibility of greater pain sensitivity and potential susceptibility for chronic pain development.

Methods: Psychophysical and anthropometric data were collected from 38 individuals with an obese body mass index (BMI) classification (BMI ≥ 30) and 41 age/sex-matched individuals of a healthy BMI (BMI < 24.

Spatial aspects of pain modulation are not disrupted in adolescents with migraine.

Objective: To compare spatial pain modulation capabilities between adolescents with and without migraine.

Background: Conditioned pain modulation (CPM) responses at the leg are similar in adolescents with versus without migraine. However, the anatomical region of testing may affect spatial pain modulation capabilities as differences in nociceptive processing between patients with migraine and healthy controls are found in local areas that are near the site of clinical pain but not in nonlocal areas.

Identification of neural and psychophysical predictors of headache reduction after cognitive behavioral therapy in adolescents with migraine.

Cognitive behavioral therapy (CBT) is a psychological intervention that involves development of coping strategies to reduce the experience of pain. Although CBT is a promising intervention to reduce headache days in patients with migraine, it may not be effective for all patients. Thus, there is a need to identify markers that could predict which patients will respond to CBT.

Alterations in Brain Function After Cognitive Behavioral Therapy for Migraine in Children and Adolescents.

Objectives: This basic mechanistic study examined the changes in brain activation and resting-state connectivity after 8 weeks of CBT in youth with migraine.

Background: Cognitive behavioral therapy (CBT) is a psychological intervention that is effective in reducing pain in migraine patients. However, the neural mechanisms underlying CBT in adolescents with migraine are not yet known.

Clinical presentation, diagnosis and polysomnographic findings in children with migraine referred to sleep clinics.

Objective: An association between migraine and sleep disturbances in children was reported, yet limited clinical data exist. The current study addresses the clinical presentation, polysomnographic (PSG) characteristics, and comorbid sleep diagnoses of children with migraine referred to the sleep clinic.

Patients: A retrospective review was performed of headache center patients evaluated by the sleep center between 2007 and 2017.

Associations of self-report and actigraphy sleep measures with experimental pain outcomes in patients with temporomandibular disorder and healthy controls.

Objective: Discrepancies between self-reported and actigraphy sleep measures are common, producing ambiguity about which are better predictors of experimental pain outcomes. The current study tested if pain intensity during and situational pain catastrophizing following experimental pain were differentially predicted by self-reported or actigraphy sleep measures in patients with chronic temporomandibular disorder (TMJD) or healthy controls (HCs).

Methods: Forty patients with TMJD and 20 HCs completed self-report sleep measures (Pittsburgh Sleep Quality Index, PSQI; Insomnia Severity Index, ISI; PROMIS Sleep-Related Impairment [SRI] and Sleep Disruption [SD]), underwent an experimental pain induction consisting of four consecutive cold-water hand immersions, and provided pain intensity and situational pain catastrophizing ratings.

Increased pain sensitivity but normal pain modulation in adolescents with migraine.

Inhibitory pain modulation has been reported to be deficient in adults across different types of chronic pain, including migraine. To determine whether a similar phenomenon occurs in youth, we performed a quantitative sensory testing investigation in adolescents with migraine (N = 19). These patients were compared to healthy adolescents with (Fam-His; N = 20) or without (Healthy; N = 29) a family history of migraine (eg, first-degree relative with migraine).