Bilateral neurogenic mechanisms following acute unilateral inflammation

The contribution of neurogenic mechanisms to inflammation has been extensively studied during the last decade, but provides no clear understanding of the bilateral changes commonly seen following unilateral stimulation. This work demonstrates that bilateral neurogenic mechanisms are a part of general host defence reactions following acute unilateral challenge, for the first time revealing that local anaesthetics applied contralaterally, might be used for therapeutic purposes i n relieving pain and inflammation. Unilateral injection of a pro-inflammatory substance (50µg of Freund's adjuvant, 50µl of 2% carrageenan, 50µg IL-1[alpha] or 50µl of 10-5 M of substance P) into a rat's knee induced a bilateral release of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (-LI) as compared to saline injection. No visual signs of inflammation are found in the non-injected knee. The same injection with pro- inflammatory substance also induced significant changes in neuropeptide-LI in cerebrospinal fluid (CSF) and plasma, indicating a general activation of the nervous system following an acute challenge. Intraperitoneal injection of 50µg of IL-1[alpha] or subcutaneous injection of 50µg of Freund's adjuvant increased CGRP-LI in CSF, in plasma and the knee joint perfusate bilaterally, while concentrations of SP- , NKA- and NPY-LI were either decreased/ increased or unchanged. Taken together, the general release of neuropeptide-LI following acute challenge may be considered a part of a general host defence reaction. To investigate further the neurogenic mechanisms involved in bilateral responses, CGRP 300 pmol was injected into the rat hindpaw. Unilateral injection of CGRP 300 pmol induces a bilateral edema formation lasting for 24h and the release of CGRP-LI on the contralateral side, the latter abolished by common sciatic nerve section. Edema formation is attenuated by injection of CGRP 300 pmol concomitantly with the antagonist to CGRP-, 5-HT2- or 5-HT3-receptors, indicating that the mast cell mechanisms are involved. Bilateral edema formation is also abolished b y intrathecal pretreatment with bicuculline, the GABAA-receptor antagonist, supporting the involvement of dorsal root reflexes. However, ipsilateral but not contralateral edema formation is also reduced by intrathecal pretreatment with the CGRP antagonist, CGRP8-37, and saline, indicating that block or dilution of neurogenic substances at the spinal cord level prevents the bilateral interaction of what might be termed cross-spinal reflexes. The existence of such reflexes is further supported by demonstrating that contralateral pretreatment with local anaesthetics (xylocain or bupivacaine) for 24h inhibited, in a dose dependent manner, the bilateral decrease in withdrawal latency and ipsilateral edema formation in carrageenan (100µl vs 50µl)-induced hindpaw inflammation. Common sciatic nerve section of the contralateral side abolished the effect of contralateral pretreatment. Contralateral treatment with local anaesthetics reduced SP-LI concentrations in perfusates following capsaicin challenge, clearly indicating spinal cord mechanisms are involved

Emotional Awareness Correlated With Number of Awakenings From Polysomnography in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome : A Pilot Study

Introduction: Unrefreshing sleep is one of the diagnostic criteria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which could be explained by sleep disorders, for example obstructive sleep apnea, reported in our previous study with polysomnography. Our previous findings also indicate difficulties in emotional regulation when measuring alexithymia by TAS-20 (Toronto Alexithymia Scale) and level of emotional awareness by LEAS (Level of Emotional Awareness Scale) in ME/CFS patients. However, the reasons for this are unknown. The purpose of this study was to investigate correlations between data from subjective emotional regulation and polysomnography. Methods: Twenty-three ME/CFS patients (5 men and 18 women) of mean age 43, and 30 matched healthy controls (9 males and 21 women) of mean age 45, filled in TAS-20, LEAS, and Hospital Depression and Anxiety Scale (HADS). A polysomnography was performed on patients but not on healthy controls. Thus, values of normal population were used for sleep evaluation in ME/CFS patients. Result: There were significant differences between patients and controls in several aspects of emotional regulation, for example LEAS-self and LEAS-total. Seventy percent of the patients had increased numbers of awakenings (shifts from any sleep stage to awake), 22% had obstructive sleep apneas, and 27% had periodic limb movements. Correlation analysis showed that number of awakenings significantly correlated with LEAS-self and LEAS-total, p < 0.01, respectively. There were no other significant correlations. Conclusion: This pilot study demonstrated significant correlations between reduced emotional awareness and number of awakenings in polysomnography. Future studies with larger cohorts need to be conducted

The Relationship Between Alexithymia and Emotional Awareness: A Meta-Analytic Review of the Correlation Between TAS-20 and LEAS

Background: Alexithymia and emotional awareness may be considered overlapping constructs and both have been shown to be related to psychological and emotional well-being. However, it is not clear how the constructs relate to each other empirically or if they may overlap more or less in different populations. The aim of this review was therefore to conduct a meta-analysis of correlations between the most commonly used measures of alexithymia (i.e., the self-report instrument Toronto Alexithymia Scale; TAS-20) and emotional awareness (i.e., the observer-rated instrument Level of Emotional Awareness Scale; LEAS) and to explore potential moderators of their relationship.Methods: Electronic databases were searched for studies published until the end of February 2018. Study samples were coded as medical conditions, psychiatric disorders and/or healthy controls and sample mean age and gender distribution were extracted. Correlations between the TAS-20 and the LEAS were subjected to a random effect of meta-analysis and moderators were explored in subgroup analyses and meta-regressions. Publication bias was considered.Results: 21 studies reporting on 28 independent samples on correlation analysis were included, encompassing a total of 2857 subjects (57% women). The aggregated correlation between TAS-20 and LEAS was r = −0.122 (95% CI [−0.180, −0.064]; Z = −4.092; p < 0.001), indicating a significant, but weak, negative relationship between the measures. Heterogeneity was moderate, but we found no indication of significant differences between patients with medical conditions, psychiatric disorders or healthy controls, nor that mean age or percentage of female subjects moderated the relationship. The overall estimate became somewhat weaker after adjusting for possible publication bias.Conclusions: Our results indicate that TAS-20 and LEAS measure different aspects of emotional functioning. The small overlap suggests that alexithymia and emotional awareness are distinct constructs of emotional well-being. Clinicians need to assess both aspects when considering treatment options for individual patients. Moreover, from the clinical standpoint, an easy reliable and valid way of measuring emotional awareness is still needed. More research should be focus on the differences between alexithymia and emotional awareness in specific conditions, but also how to integrate self-report instrument and observed based measures in a clinical situation

Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection

The global pandemic of SARS-CoV-2 has affected several hundred million people, and many infected people have suffered from a milder initial infection but have never fully recovered. This observational study investigates the pain burden in sufferers of post-COVID-19 syndrome after a milder initial infection. One hundred post-COVID-19 patients filled out questionnaires regarding sociodemographic data, previous comorbidities, present pharmacological treatment, pain intensity and pain localisation. Health-related quality of life, fatigue, emotional status, and insomnia were measured by validated questionnaires. Multiple post-COVID-19 symptoms, including post-exertional malaise, were evaluated by a symptom questionnaire. Among the 100 participants (mean age 44.5 years), 82% were women, 61% had higher education, and 56% were working full or part time. Nine participants reported previous pain or inflammatory conditions. Among the most painful sites were the head/face, chest, lower extremities, and migrating sites. Generalised pain was self-reported by 75 participants and was estimated in 50 participants. Diagnosis of fibromyalgia according to the 2016 criteria was suspected in 40 participants. Subgroup analyses indicated that comorbidities might play a role in the development of pain. In conclusion, a major part of sufferers from post-COVID-19 syndrome develop pain, and in addition to its many disabling symptoms, there is an urgent need for pain management in post-COVID-19 syndrome

Do Comorbidities and Daily Medication before SARS-CoV-2 Infection Play a Role in Self-Reported Post-Infection Symptoms?

This study investigated the associations between health status before SARS-CoV-2 infection and persistent symptoms after acute infection. Data were collected from participants older than 18 years and more than 28 days after acute SARS-CoV-2 infection using an online survey. Sociodemographic data, comorbidities, and daily medication before infection, as well as acute and persistent symptoms were analysed. Among the 1050 participants (mean age 41 years, 88% women, 56% with higher education, 93% working), 538 (51%) reported being healthy and 762 (73%) reported not taking any daily medication prior to infection. Positive laboratory testing was reported by 965 (92%) participants; asymptomatic infection was reported by 30 (3%); and 999 (95%) stayed at home during their acute infection. Reduced physical capacity (40%), fatigue (39%), cognitive difficulties (30–34%), altered sense of smell (24%), headache (20%), tachycardia (20%), unstable mood (19%), hair loss (17%), and insomnia (17%) were the most often reported symptoms. Those taking daily medication before infection reported increased frequency of both acute and persistent symptoms, except for decreased frequency of persistent altered smell and taste. The presence of persistent symptoms was predicted by taking daily medication before infection and by the total number of acute symptoms. Comorbidities before infection did not predict persistent symptoms. Therefore, the role of medication needs further investigation in both acute SARS-CoV-2 infection and post-COVID-19 condition