Uncategorized

BACKGROUND Pericardial cyst is a rare benign mass of the mediastinum. More than two-thirds of pericardial cysts are located in the right cardiophrenic angle and less than one-third in the left cardiophrenic angle. Most cases are asymptomatic and discovered incidentally during to thoracic imaging such as chest X-ray, CT scans, and transthoracic echocardiograms. When pericardial cysts present with symptoms, they are often persistent and non-specific and include chest pain, dyspnea, and persistent cough. The optimal management of pericardial cysts is unclear, and no large studies regarding safety, efficacy, and long-term follow-up exist. Management strategies include cyst resection with sternotomy, thoracotomy or video-assisted thoracic surgery, cyst aspiration, and sclerosis after aspiration. The optimal mode of follow-up for asymptomatic cases is also unclear. Here, we present a case of a large pericardial cyst in the left cardiophrenic angle in a middle-aged Danish woman with persistent and unresolved dyspnea and chest pain. CASE REPORT A 57-year-old woman was referred for transthoracic echocardiography because of year-long cough and left-sided chest pain, which were exacerbated in the supine position. The echocardiography revealed a large cyst-like structure over the left ventricle. A cardiac CT scan and MRI scan were performed, confirming the presence of a large pericardial cyst with no communication with the pericardium. The cyst was surgically removed via thoracotomy. CONCLUSIONS Pericardial cysts should be considered as a rare differential diagnosis, giving rise to common cardio-pulmonary symptoms such as chest pain, dyspnea, and cough.

Background Bone morphogenetic protein-4 (BMP4) plays a critical role in regulating neuronal and glial activity in the course of spinal cord injury (SCI). However, the underlying cause and cellular source of the BMP4 accumulation at the injured spinal cord remains unclear. Method Firstly, the SCI patients and healthy donors were enrolled to test their plasma concentrations of BMP2/4/7 and the antagonist Noggin using enzyme linked immunosorbent assay (ELISA). Secondly, rats were randomly divided into 3 groups: the Sham group (T9 laminectomy without SCI), the SCI group and the SCI+CLL group (circulating monocytes depletion before SCI). For each group, Basso-Beattie-Bresnahan (BBB) scales and immuno-histochemistry were employed to evaluate the functional and histological changes; ELISA was conducted to test the expression patterns of BMP4, Noggin and neurofilament light polypeptide (NEFL) both in blood and cerebrospinal fluid (CSF); western blotting and flow cytometry were further performed to investigate the BMP4 expressions in the spinal cord, and particularly in the circulating monocytes and infiltrating monocyte-derived macrophages (MDMs) respectively. Results Firstly, the level of BMP4, instead of BMP2/7 was statistically higher in the SCI patients than in the healthy donors. Secondly, compared with the Sham group, rats in the SCI group developed a persistent decline in the BBB scores, together with evident necrosis and the accumulation of mononuclear cells at the contusion site. Additionally, both plasma and CSF levels of BMP4, Noggin and NEFL displayed notable elevations throughout two weeks after SCI, and positive correlations could be found between blood and CSF in all indicators above. Importantly, BMP4 expression displayed upregulation in the injured spinal cord, and the percentage of BMP4 positive circulating monocytes and infiltrating MDMs were both higher in the SCI group than in the Sham group. Finally, in the SCI+CLL group, depletion of circulating monocytes effectively relieved BMP4 accumulation in the injured spinal cord. Conclusion Following SCI, infiltrating MDMs provide an important source of BMP4 in the injured spinal cord. Depletion of circulating monocytes effectively downregulates BMP4 levels in the spinal cord at the early stage of SCI, which might serve as a potential therapeutic target.

In recent years, the use of topical morphine gel has increased in the palliative care setting to reduce pain in chronic wounds and fungating tumours. However, there is a paucity of evidence to support its effectiveness. Epidermolysis bullosa (EB) is a rare genetic skin fragility disorder characterised by painful chronic wounds. Adequate control of wound pain can be challenging in this patient group due to other complexities associated with the more severe sub-types of the disease. Topical morphine gel has been used as an adjunct therapy in a small number of EB patients in our tertiary centre in an attempt to improve pain control and quality of life. The purpose of this paper is to demonstrate the efficacy of topical morphine gel used in a variety of EB wounds as well as patient reported reduction in pain through a series of case studies. The case studies suggest a positive effect of topical morphine gel on painful wounds across a spectrum of EB subtypes.

Atopic dermatitis (AD) is a common chronic pruritic inflammatory skin disease that relies on neuro-immune communication while neuronal mechanism-based therapeutic attempts remain lacking. We sought to investigate the efficacy of intravenous lidocaine therapy on AD and underlying neuro-immune mechanism.

Men and women with chronic pain report increased alcohol use and are more likely to be diagnosed with alcohol use disorder. The relationship between alcohol use and pain is bidirectional with alcohol used as an analgesic, but chronic intake increasing pain. Sex differences in the relationship between chronic pain and alcohol are reported in the clinical and preclinical literature, but due to this bidirectional relationship, it is challenging to investigate the mechanisms that contribute to these differences. Thus, animal models of chronic pain are needed to characterize the efficacy of ethanol as an analgesic in males and females. The current experiments tested the hypothesis that ethanol would differentially reduce pain behaviors in male and female mice in chronic neuropathic pain.

Prolonged experimental pain can help assess cortical mechanisms underlying the transition from acute to chronic pain such as resting-state functional connectivity (rsFC), especially in early stages. This crossover study determined the effects of 24-hour-capsaicin-induced pain on the default mode network rsFC, a major network in the dynamic pain connectome. Electroencephalographic rsFC measured by Granger causality was acquired from 24 healthy volunteers (12 women) at baseline, 1hour, and 24hours following a control or capsaicin patch on the right forearm. The control patch was received maximum one week before the capsaicin patch. Following 24hours, the patch was cooled and later heated to assess rsFC changes in response to pain relief and facilitation, respectively. Compared to baseline, decreased rsFC at alpha oscillations (8-10Hz) was found following 1hour and 24hours of capsaicin application for connections projecting from medial prefrontal cortex (mPFC) and right angular gyrus (rAG) but not left angular gyrus (lAG) or posterior cingulate cortex (PCC): mPFC-PCC (1hour:P<0.001, 24hours_P=0.002), mPFC-rAG (1hour:P<0.001, 24hours_P=0.001), rAG-mPFC (1hour:P<0.001, 24hours_P=0.001), rAG-PCC (1hour:P<0.001, 24hours_P=0.004). Comparable decreased rsFC following 1hour and 24hours (P≤0.008) was found at beta oscillations, however, decreased projections from PCC were also found: PCC-rAG (P≤0.005) and PCC-lAG (P≤0.006). Pain NRS scores following 24hours (3.7±0.4) was reduced by cooling (0.3±0.1, P=0.004) and increased by heating (4.8±0.6, P=0.016). However, neither cooling nor heating altered rsFC. This study shows that 24hours of experimental pain induces a robust decrease in DMN connectivity that persists during pain relief or facilitation suggesting a possible shift to attentional and emotional processing in persistent pain. Perspective: This article shows decreased DMN connectivity that might reflect possible attentional and emotional changes during acute and prolonged pain. Understanding these changes could potentially help clinicians in developing therapeutic methods that can better target these attentional and emotional processes before developing into more persistent states.

Previous studies have reported that L5/L6 spinal nerve ligation (SNL), but not L5 spinal nerve transection (SNT), enhances anoctamin-1 in injured and uninjured dorsal root ganglia (DRG) of rats suggesting some differences in function of the type of nerve injury. The role of bestrophin-1 in these conditions is unknown. The aim of this study was to investigate the role of bestrophin-1 in rats subjected to L5 spinal nerve transection (SNT) and L5/L6 spinal nerve ligation (SNL). SNT up-regulated bestrophin-1 protein expression in injured L5 and uninjured L4 DRG at day 7, whereas it enhanced GAP43 mainly in injured, but also in uninjured DRG. In contrast, SNL enhanced GAP43 at day 1 and 7, while bestrophin-1 expression increased only at day 1 after nerve injury. Accordingly, intrathecal injection of the bestrophin-1 blocker CaCC (1-10 µg) reverted SNT- or SNL-induced tactile allodynia in a concentration-dependent manner. Intrathecal injection of CaCC (10 µg) prevented SNT-induced upregulation of bestrophin-1 and GAP43 at day 7. In contrast, CaCC did not affect SNL-induced up-regulation of GAP43 nor bestrophin-1. Bestrophin-1 was mainly expressed in small- and medium-size neurons in naïve rats, while SNT increased bestrophin-1 immunoreactivity in CGRP+, but not in IB4+ neuronal cells in DRG. Intrathecal injection of bestrophin-1 plasmid (pCMVBest) induced tactile allodynia and increased bestrophin-1 expression in DRG and spinal cord in naïve rats. CaCC reversed bestrophin-1 overexpression-induced tactile allodynia and restored bestrophin-1 expression. Our data suggest that bestrophin-1 plays a relevant role in neuropathic pain induced by SNT, but not by SNL. Perspective: SNT, but not SNL, up-regulates bestrophin-1 and GAP43 protein expression in injured L5 and uninjured L4 DRG. Moreover, SNT increases bestrophin-1 immunoreactivity in CGRP+ neurons in DRG, while bestrophin-1 overexpression induces allodynia. CaCC reduces allodynia and restores bestrophin-1 expression induced by bestrophin-1 transfection. Our data suggest that spinal bestrophin-1 in DRG is differentially regulated depending on the neuropathic pain model.

Our understanding of neuropathic itch is limited, due to the lack of relevant animal models. Patients with cutaneous T-cell lymphoma (CTCL) suffer from severe itching. Here we characterize a mouse model of chronic itch with remarkable lymphoma growth, immune cell accumulation, and persistent pruritus. Intradermal CTCL inoculation produces time-dependent changes in nerve innervations in lymphoma-bearing skin. In the early-phase (20 days), CTCL causes hyper-innervations in the epidermis. However, chronic itch is associated with loss of epidermal nerve fibers in the late-phases (40 and 60 days). CTCL is also characterized by marked nerve innervations in mouse lymphoma. Blockade of C-fibers reduced pruritus at early- and late-phases, whereas blockade of A-fibers only suppressed late-phase itch. Intrathecal gabapentin injection reduced late-phase but not early-phase pruritus. IL-31 is upregulated in mouse lymphoma, while its receptor Il31ra was persistently upregulated in Trpv1-expressing sensory neurons in CTCL mice. Intratumoral anti-IL-31 treatment effectively suppressed CTCL-induced scratching and alloknesis (mechanical itch). Finally, intrathecal administration of TLR4 antagonist attenuated pruritus in early and late phases and in both sexes. Collectively, we have established a mouse model of neuropathic and cancer itch with relevance to human disease. Our findings also suggest distinct mechanisms underlying acute, chronic, and neuropathic itch.

Previous functional magnetic resonance imaging studies have substantiated changes in multiple brain regions of functional activity in patients with vestibular migraine. However, few studies have assessed functional connectivity within and between specific brain networks in vestibular migraine.

Diseases of joints are among the most frequent causes of chronic pain. In the course of joint diseases the peripheral and the central nociceptive system develop persistent hyperexcitability (peripheral and central sensitization). This review addresses the mechanisms of spinal sensitization evoked by arthritis. Electrophysiological recordings in anaesthetized rats from spinal cord neurons with knee input in a model of acute arthritis showed that acute spinal sensitization is dependent on spinal glutamate receptors (AMPA, NMDA and metabotropic glutamate receptors) and supported by spinal actions of neuropeptides such as neurokinins and CGRP, by prostaglandins, and by proinflammatory cytokines. In several chronic arthritis models (including immune-mediated arthritis and osteoarthritis) spinal glia activation was observed to be coincident with behavioral mechanical hyperalgesia which was attenuated or prevented by intrathecal application of minocycline, fluorocitrate and pentoxyfylline. Some studies identified specific pathways of micro- and astroglia activation such as the purinoceptor- (P X -) cathepsin S/CX CR1 pathway, the mobility group box-1 protein (HMGB1) and toll-like receptor 4 (TLR4) activation, spinal NFκB/p65 activation and others. The spinal cytokines TNF, interleukin-6, interleukin-1β and others form a functional spinal network characterized by an interaction between neurons and glia cells which is required for spinal sensitization. Neutralization of spinal cytokines by intrathecal interventions attenuates mechanical hyperalgesia. This effect may in part result from local suppression of spinal sensitization and in part from efferent effects which attenuate the inflammatory process in the joint. In summary, arthritis evokes significant spinal hyperexcitability which is likely to contribute to the phenotype of arthritis pain in patients.