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Pituitary adenylate cyclase-activating polypeptide (PACAP) is found in two functional isoforms, namely PACAP38 and PACAP27. The migraine-inducing properties of PACAP38 are well studied. However, it is not known whether the lesser-known and under-studied protein isoform, PACAP27, can also induce migraine attacks. Here, we studied the effect of human PACAP27 infusion on induction of migraine in a provocation model.
Blood pressure (BP), pulse, electrocardiogram (ECG), and clinical cardiovascular (CV) outcomes in patients with episodic or chronic migraine treated for up to 6 months with galcanezumab compared to placebo were evaluated.
The aim of this study was to analyze the potential association between personality traits and onabotulinumtoxin A (onabotA) response in patients with chronic migraine (CM).
Provoked vestibulodynia (PVD) is a chronic vulvo-vaginal pain condition affecting 8% of premenopausal women. Cognitive-behavioral therapy (CBT) is effective in managing pain and associated sexual and psychological symptoms, and a recent study found group mindfulness-based cognitive therapy (MBCT) to be equivalent. Our goal was to examine the long-term outcomes of these treatments and to explore mediators of change.
Adolescents who undergo major surgery experience high rates of disabling acute and chronic postsurgical pain (CPSP). However, little is known about the subacute period when acute to chronic pain transition occurs.
Reported pain intensity depends not only on stimulus intensity but also on previously experienced pain. A painfully hot temperature applied to the skin evokes a lower subjective pain intensity if immediately preceded by a higher temperature, a phenomenon called offset analgesia. Previous work indicated that prior pain experience can also increase subsequent perceived pain intensity. Therefore, we examined whether a given noxious stimulus is experienced as more intense when it is preceded by an increase from a lower temperature. Using healthy volunteer subjects, we observed a disproportionate increase in pain intensity at a given stimulus intensity when this intensity is preceded by a rise from a lower intensity. This disproportionate increase is similar in magnitude to that of offset analgesia. We call this effect onset hyperalgesia. Control stimuli, in which a noxious temperature is held constant, demonstrate that onset hyperalgesia is distinct from receptor or central sensitization. The absolute magnitudes of offset analgesia and onset hyperalgesia correlate with each other but not with the noxious stimulus temperature. Finally, the magnitude of both offset analgesia and onset hyperalgesia depends on preceding temperature changes. Overall, this study demonstrates that the perceptual effect of a noxious thermal stimulus is influenced in a bidirectional manner depending upon both the intensity and direction of change of the immediately preceding thermal stimulus.
It is known that perivascular application of CGRP induces cerebral vasodilatation. However, it is unclear whether intravenous alfa CGRP (αCGRP) induces changes in cerebral and systemic hemodynamics. Therefore, we studied the influence of an αCGRP intravenous infusion at a rate of 1.5 mcg/min in 20 min on mean arterial velocity in the middle cerebral artery (vm MCA) and in the posterior cerebral artery (vm PCA) in twenty healthy subjects using transcranial Doppler (TCD). We found out that αCGRP decreased vm MCA ( < 0.001), vm PCA ( < 0.001), mean arterial pressure (MAP) ( < 0.001) and end-tidal CO (Et-CO) ( = 0.030). The heart rate (HR) increased during αCGRP infusion ( < 0.001). In addition, we found a positive relationship between Et-CO and vm MCA ( = 0.001) as well as vm PCA ( = 0.043). In our view, αCGRP induces changes in cerebral and systemic circulation in healthy volunteers. It might cause vasodilatation of MCA and PCA and a compensatory decrease of Et-CO to αCGRP related hemodynamic changes.
There is growing consensus that pain in pediatric inflammatory bowel disease (IBD) is not fully explained by disease-related processes. However, previous studies have largely measured individual biological, psychological, or social risk factors for pain in isolation. Further, not all youth with IBD presenting to clinic will report presence of pain, and those who do vary in their reports of pain intensity. This study therefore extends prior research by determining biopsychosocial correlates of both presence and intensity of pain in adolescents with IBD, in order to inform targeted pain management intervention approaches. Adolescents with IBD followed at SickKids, Toronto, and their parents were consecutively enrolled from outpatient clinic. IBD characteristics (diagnosis, time since diagnosis, patient-reported disease activity) were collected. Adolescents reported on current pain (NRS-10), internalizing symptoms (Strengths and Difficulties Questionnaire), and pain catastrophizing (Pain Catastrophizing Scale-Child). Parents reported on protective responses to child pain (Adult Responses to Child Pain) and pain catastrophizing (Pain Catastrophizing Scale-Child). Hurdle models were conducted to examine predictors of presence and intensity of pain in the same model. Biological (patient-reported disease activity, IBD diagnosis subtype, illness duration), psychological (internalizing symptoms, pain catastrophizing), and social (parent pain catastrophizing, parent protective responses) factors were entered as predictors, adjusting for age and sex. Participants included 100 adolescents (12-18; = 15 years) with IBD (60% Crohn's Disease, 40% Ulcerative Colitis or IBD-unclassified) and 76 parents. The majority of the sample was in clinical remission or reported minimal symptoms. Half of participants reported no current pain; for those reporting pain, intensity ranged 1-7 ( = 3.43, SD = 1.98). Disease activity (OR = 53.91, < 0.001) and adolescent internalizing symptoms (OR = 7.62, = 0.03) were significant predictors of presence of pain. Disease activity (RR = 1.37, = 0.03) and parent protective responses (RR = 1.45, = 0.02) were significant predictors of intensity of pain. Results suggest that the experience of pain in pediatric IBD is biopsychosocially determined. Patient-reported disease activity and internalizing symptoms predicted presence of pain, while disease activity and parent protective responses predicted intensity of pain. While medical intervention in pediatric IBD is focused on disease management, results suggest that depression/anxiety symptoms as well as parent protective responses may be important targets of pain management interventions in pediatric IBD.
Entraining alpha activity with rhythmic visual, auditory, and electrical stimulation can reduce experimentally induced pain. However, evidence for alpha entrainment and pain reduction in patients with chronic pain is limited. This feasibility study investigated whether visual alpha stimulation can increase alpha power in patients with chronic musculoskeletal pain and, secondarily, if chronic pain was reduced following stimulation. In a within-subject design, 20 patients underwent 4-min periods of stimulation at 10 Hz (alpha), 7 Hz (high-theta, control), and 1 Hz (control) in a pseudo-randomized order. Patients underwent stimulation both sitting and standing and verbally rated their pain before and after each stimulation block on a 0-10 numerical rating scale. Global alpha power was significantly higher during 10 Hz compared to 1 Hz stimulation when patients were standing ( = -6.08, < 0.001). On a more regional level, a significant increase of alpha power was found for 10 Hz stimulation in the right-middle and left-posterior region when patients were sitting. With respect to our secondary aim, no significant reduction of pain intensity and unpleasantness was found. However, only the alpha stimulation resulted in a minimal clinically important difference in at least 50% of participants for pain intensity (50%) and unpleasantness ratings (65%) in the sitting condition. This study provides initial evidence for the potential of visual stimulation as a means to enhance alpha activity in patients with chronic musculoskeletal pain. The brief period of stimulation was insufficient to reduce chronic pain significantly. This study is the first to provide evidence that a brief period of visual stimulation at alpha frequency can significantly increase alpha power in patients with chronic musculoskeletal pain. A further larger study is warranted to investigate optimal dose and individual stimulation parameters to achieve pain relief in these patients.
Chronic post-surgical pain (CPSP) is one of the post-surgical complications of a Cesarean section. Despite the high rates of Cesarean section worldwide, the incidence of CPSP and the risk factors for this condition remain relatively unknown. The objective of this study was to calculate the incidence of CPSP in women submitted to Cesarean section and to analyze the associated risk factors.