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The amygdala is central to emotional processing of sensory stimuli, including pain. Because recent findings suggest that individual differences in emotional processes play a part in the development of chronic pain, a better understanding of the individual patterns of functional connectivity that make individuals susceptible to emotionally modulated facilitation of pain is needed. We therefore investigated the neural correlates of individual differences in emotional pain facilitation using resting-state functional magnetic resonance imaging (rs-fMRI) with amygdala seed.Thirty-seven participants took part in 3 separate sessions, during which pain sensitivity was tested (session 1), participants underwent rs-fMRI (session 2), and emotional pain modulation was assessed (session 3). Amygdala served as seed for the rs-fMRI analysis and whole-brain voxelwise connectivity was tested. Pain modulatory scores were entered as regressor for the group analysis.Stronger connectivity of the amygdala to S1/M1, S2/operculum, and posterior parietal cortex at rest characterized individuals who showed greater pain facilitation by negative emotions. When comparing the amygdala networks associated with pain unpleasantness and with pain intensity modulation, most of the identified areas were equally related to either pain rating type; only amygdala connectivity to S1/M1 was found to predict pain intensity modulation specifically.We demonstrate that trait-like patterns of functional connectivity between amygdala and cortical regions involved in sensory and motor responses are associated with the individual amplitude of pain facilitation by negative emotional states. Our results are an early step towards improved understanding of the mechanisms that give rise to individual differences in emotional pain modulation.
Learn More >To provide updated evidence-based recommendations about when to obtain neuroimaging in patients with migraine.
Learn More >Many individuals with migraine report symptoms of dry eye (DE). However, it is not known whether DE profiles are similar between individuals with and without migraine. To bridge this gap, we evaluated symptoms and signs of DE, including symptoms suggestive of nerve dysfunction, in a large group of individuals with DE symptoms, and compared profiles between individuals with migraine and those without migraine or headache.
Learn More >Both temporomandibular disorders myalgia (TMDM) and fibromyalgia (FM) have been linked to central and peripheral changes in serotonin availability. The precursor of serotonin, tryptophan (TRP), is mainly catabolized via another pathway to produce kynurenine (KYN), but whether changes of this pathway are present in TMDM and FM are still unclear.
Learn More >Galcanezumab is a humanized immunoglobulin G (IgG) monoclonal antibody (mAb) indicated for the prevention of migraine that binds to calcitonin gene-related peptide. A population pharmacokinetic (PK) analysis was performed to characterize galcanezumab PK using data pooled from 7 clinical studies. Clinical studies included healthy individuals and patients with episodic or chronic migraine who were administered between 5 and 300 mg galcanezumab. The PK data were analyzed using nonlinear mixed-effects modeling. Galcanezumab concentration-time data were described with a 1-compartment model with first-order absorption following subcutaneous administration and linear elimination. At the median body weight of 74 kg, the estimated population apparent clearance (CL/F) was 0.00785 L/h (34% IIV), the apparent volume of distribution was 7.33 L (34% IIV), and half-life was 27 days. Patient body weight was found to have a modest effect of CL/F, with median galcanezumab concentrations being lower in the heaviest patients compared to the lightest patients, but this outcome was determined not to be clinically relevant in the context of model-estimated random variability. Dosing adjusted for body weight is not warranted in adults. Age, sex, race/ethnicity, immunogenicity, renal/hepatic markers, and injection-site location did not affect galcanezumab PK. In conclusion, galcanezumab exhibits PK parameters typical for an IgG mAb administered subcutaneously. The population PK model developed in this study demonstrates that galcanezumab exhibits linear PK that was not influenced in a clinically relevant manner by the patient factors evaluated.
Learn More >Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a common chronic pelvic disorder with sensory symptoms of urinary urgency, frequency, and pain, indicating a key role for hypersensitivity of bladder-innervating sensory neurons. The inflammatory mast cell mediator histamine has long been implicated in IC/BPS, yet the direct interactions between histamine and bladder afferents remain unclear. Here we show, using a mouse bladder afferent preparation, that intravesical histamine enhanced the mechanosensitivity of sub-populations of afferents to bladder distension. Histamine also recruited 'silent afferents', which were previously unresponsive to bladder distension. Furthermore, intravesical histamine enhanced activation of dorsal horn neurons within the lumbosacral spinal cord, indicating increased afferent signaling into the central nervous system. qRT-PCR revealed significant expression of histamine receptor subtypes () in mouse lumbosacral dorsal root ganglia (DRG), bladder detrusor smooth muscle, mucosa, and isolated urothelial cells. In DRG, was the most abundantly expressed. Acute histamine exposure evoked calcium influx in select populations of DRG neurons but did not elicit calcium transients in isolated primary urothelial cells. Histamine-induced mechanical hypersensitivity was abolished in the presence of the histamine H receptor (HR) antagonist pyrilamine and was not present in preparations from mice lacking the TRPV1 receptor. Together, these results indicate that histamine enhances the sensitivity of bladder afferents to distension via interactions with HR and TRPV1. This hypersensitivity translates to increased sensory input and activation in the spinal cord, which may underlie the symptoms of bladder hypersensitivity and pain experienced in IC/BPS.
Learn More >Corneal confocal microscopy is a rapid non-invasive ophthalmic imaging technique that identifies peripheral and central neurodegenerative disease. Quantification of corneal sub-basal nerve plexus morphology, however, requires either time-consuming manual annotation or a less-sensitive automated image analysis approach. We aimed to develop and validate an artificial intelligence-based, deep learning algorithm for the quantification of nerve fibre properties relevant to the diagnosis of diabetic neuropathy and to compare it with a validated automated analysis program, ACCMetrics.
Learn More >Patients with chronic pain often report being sensitive to pain at night before falling asleep, a time when the synchronization of cortical activity is initiated. However, how cortical activity relates to pain sensitivity is still unclear. Since sleep is characterized by enhanced cortical delta power, we hypothesized that enhanced cortical delta power may be an indicator of intensified pain. To test this hypothesis, we used pain thresholds tests, EEG/electromyogram recordings, c-Fos staining and chemogenetic and pharmacological techniques in mice. We found that sleep deprivation or pharmacologic enhancement of EEG delta power by reserpine and scopolamine dramatically decreased mechanical pain thresholds, but not thermal withdrawal latency, in a partial sciatic-nerve ligation model of neuropathic pain mice. On the contrary, suppression of EEG delta power using a wake-promoting agent modafinil significantly attenuated mechanical allodynia. Moreover, when EEG delta power was enhanced, c-Fos expression decreased in most regions of the cortex, except the anterior cingulate cortex (ACC), where c-Fos was increased in the somatostatin and parvalbumin positive GABAergic neurons. Chemogenetic activation of GABAergic neurons in ACC enhanced EEG delta power and lowered mechanical pain thresholds simultaneously in naïve mice. However, chemogenetic inhibition of ACC GABAergic neurons could not block mechanical allodynia. These results provided compelling evidence that elevated EEG delta power is accompanied with aggravated neuropathic pain, whereas decreased delta power attenuated it, suggesting that enhanced delta power can be a specific marker of rising chronic neuropathic pain and that wake-promoting compounds could be used as analgesics in the clinic.
Learn More >Pain catastrophizing is an important predictor of pain-related outcomes. Caregiver and child levels of catastrophizing about child chronic pain are associated cross-sectionally, yet predictive associations testing interpersonal influences within caregiver-child dyads are lacking. The present study tested caregiver and child influences on partner catastrophizing about child pain over 1 month following initiation of interdisciplinary pain treatment and examined whether change in pain catastrophizing was associated with child pain interference.
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