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 panel of basic scientists, when challenged to explain what was known about how sex hormones affect the nervous system, focused on two hormones: estrogen and oxytocin. Notably, other hormones, such as progesterone, testosterone, and vasopressin, are less well studied but are also highlighted in this review. When discussing what new therapeutic agent might be an alternative to hormone therapy and menopause replacement therapy for migraine treatment, the panel pointed to oxytocin delivered as a nasal spray. Overall, the conclusion was that progress in the preclinical study of hormones on the nervous system has been challenging and slow, that there remain substantial gaps in our understanding of the complex roles sex hormones play in migraine, and that opportunities remain for improved or novel therapeutic agents. Manipulation of sex hormones, perhaps through biochemical modifications where its positive effects are selected for and side effects are minimized, remains a theoretical goal, one that might have an impact on migraine disease and other symptoms of menopause. This review is a call to action for increased interest and funding for preclinical research on sex hormones, their metabolites, and their receptors. Interdisciplinary research, perhaps facilitated by a collaborative communication network or panel, is a possible strategy to achieve this goal.

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. Participants also wore an actigraphy watch and completed sleep diaries for seven days, which were averaged for actigraphic indices of total sleep time, sleep efficiency, wake after sleep onset, and self-reported sleep quality and restfulness. RESULTS: Individuals with TMJD reported higher pain intensity during experimental pain (M = 65.81 vs. 47.77, p = .007) and self-reported worse sleep compared to HCs (all p's < 0.02, Cohen's D = 0.73-1.25). No group differences emerged for actigraphy measures (all p's > 0.05, Cohen's D = 0.05-0.53). Sleep variables did not interact with group to predict responses to experimental pain (all p's > 0.05). Across groups, PROMIS-SRI predicted pain intensity (ß = 0.36, p = .008) and catastrophizing (ß = 0.36, p = .009) after controlling for multiple comparisons, smoking, medications, and age. CONCLUSION: Self-reported sleep (but not actigraphy) measures differentiate patients with TMJD from HCs. Sleep-related interference may place people at particular risk for higher pain intensity and catastrophizing following experimental pain.

Pronociceptive pain modulation in patients with painful chemotherapy-induced polyneuropathy.

CONTEXT: Several chemotherapy agents induce polyneuropathy that is painful for some patients, but not for others. We assumed that these differences might be attributable to varying patterns of pain modulation. OBJECTIVES: The aim of the present study was to evaluate pain modulation in such patients. METHODS: Twenty-seven patients with chemotherapy-induced polyneuropathy were tested for detection thresholds (cold, warm, and mechanical) in both the forearm and foot, as well as for heat pain threshold, mechanical temporal summation (TS), and conditioned pain modulation (CPM; also known as the diffuse noxious inhibitory control-like effect), which were tested in the upper limbs. RESULTS: Positive correlations were found between clinical pain levels and both TS (r=0.52, P=0.005) and CPM (r=0.40, P=0.050) for all patients. In addition, higher TS was associated with less efficient CPM (r=0.56, P=0.004). The group of patients with painful polyneuropathy (n=12) showed a significantly higher warm detection threshold in the foot (P=0.03), higher TS (P<0.01), and less efficient CPM (P=0.03) in comparison to the group with nonpainful polyneuropathy. CONCLUSION: The painfulness of polyneuropathy is associated with a "pronociceptive" modulation pattern, which may be primary to the development of pain. The higher warm sensory thresholds in the painful polyneuropathy group suggest that the severity of polyneuropathy may be another factor in determining its painfulness.