IL-4 Deficiency Is Associated with Mechanical Hypersensitivity in Mice

Interleukin-4 (IL-4) is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko) mice to characterize their pain behavior before and after chronic constriction injury (CCI) of the sciatic nerve as a model for neuropathic pain. We investigated opioid responsivity and measured cytokine and opioid receptor gene expression in the peripheral and central nervous system (PNS, CNS) of IL-4 ko mice in comparison with wildtype (wt) mice. Naïve IL-4 ko mice displayed tactile allodynia (wt: 0.45 g; ko: 0.18 g; p<0.001), while responses to heat and cold stimuli and to muscle pressure were not different. No compensatory changes in the gene expression of tumor necrosis factor-alpha (TNF), IL-1β, IL-10, and IL-13 were found in the PNS and CNS of naïve IL-4 ko mice. However, IL-1β gene expression was stronger in the sciatic nerve of IL-4 ko mice (p<0.001) 28 days after CCI and only IL-4 ko mice had elevated IL-10 gene expression (p = 0.014). Remarkably, CCI induced TNF (p<0.01), IL-1β (p<0.05), IL-10 (p<0.05), and IL-13 (p<0.001) gene expression exclusively in the ipsilateral spinal cord of IL-4 ko mice. The compensatory overexpression of the anti-inflammatory and analgesic cytokines IL-10 and IL-13 in the spinal cord of IL-4 ko mice may explain the lack of genotype differences for pain behavior after CCI. Additionally, CCI induced gene expression of μ, κ, and δ opioid receptors in the contralateral cortex and thalamus of IL-4 ko mice, paralleled by fast onset of morphine analgesia, but not in wt mice. We conclude that a lack of IL-4 leads to mechanical sensitivity; the compensatory hyperexpression of analgesic cytokines and opioid receptors after CCI, in turn, protects IL-4 ko mice from enhanced pain behavior after nerve lesion

Systematic review with meta-analysis: cytokines in fibromyalgia syndrome

<p>Abstract</p> <p>Background</p> <p>To perform a systematic review and meta-analysis on cytokine levels in patients with fibromyalgia syndrome (FMS).</p> <p>Methods</p> <p>Through December 2010 we systematically reviewed the databases PubMed, MEDLINE, and PsycINFO and screened the reference lists of 22 review articles for suitable original articles. Original articles investigating cytokines in patients with FMS were included. Data were extracted by two independent authors. Differences of the cytokine levels of FMS patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed applying methodological scores: modified Center of Evidence Based Medicine, Newcastle-Ottawa-Scale, and Würzburg Methodological Quality Score.</p> <p>Results</p> <p>Twenty-five articles were included investigating 1255 FMS patients and 800 healthy controls. Data of 13/25 studies entered meta-analysis. The overall methodological quality of studies was low. The results of the majority of studies were not comparable because methods, investigated material, and investigated target cytokines differed. Systematic review of the selected 25 articles revealed that FMS patients had higher serum levels of interleukin (IL)-1 receptor antagonist, IL-6, and IL-8, and higher plasma levels of IL-8. Meta-analysis of eligible studies showed that FMS patients had higher plasma IL-6 levels compared to controls (SMD = -0.34 [-0.64, -0.03] 95% CI; p = 0.03). The majority of investigated cytokines were not different between patients and controls.</p> <p>Conclusions</p> <p>The pathophysiological role of cytokines in FMS is still unclear. Studies of higher quality and with higher numbers of subjects are needed.</p

There is no functional small-fibre neuropathy in prurigo nodularis despite neuroanatomical alterations

Prurigo nodularis (PN) is a pruritic condition with altered epidermal neuroanatomy as demonstrated previously. Here we elucidated neuroimmunological mechanisms by combining functional, morphological and gene expression experiments in twelve subjects with PN and eight healthy controls. Subjects with PN showed a reduced intra‐epidermal nerve fibre density (IENFD) in lesional skin. Quantitative sensory testing indicated maintenance of somatosensory function compared to controls. None of the tested molecular markers including the neuron‐distracting SEMA3A and neuron‐attracting NGF were altered in lesional vs non‐lesional skin in PN subjects. Accordingly, we speculate that scratching may contribute to reduced IENFD rather than an authentic endogenous neuropathy.FSW - Self-regulation models for health behavior and psychopathology - ou

Опыт ведения пациентов с болезнью Фабри после изменения дозы или смены препарата в процессе проведения ферментозаместительной терапии

В связи с перебоями в поставках агалсидазы бета в 2009 г. многие пациенты с болезнью Фабри (БФ) были переведены на терапию меньшими дозами этого фермента или на лечение другим ферментом – агалсидазой альфа. В настоящем наблюдательном исследовании проведена оценка изменения состояния «таргетных» органов и симптомов, возникающих вследствие снижения доз или смены препарата на агалсидазу альфа. Под наблюдением находились 105 взрослых пациентов с БФ, получавшие агалсидазу бета (в дозе 1 мг / кг массы тела) в течение 1 года и более, которые были неслучайным образом разделены на тех, кто продолжил лечение по данной схеме (группа обычных доз, n = 38), тех, кому доза была снижена до 0,3–0,5 мг / кг (группа сниженных доз, n = 29), и тех, которые были переведены на лечение агалсидазой альфа в дозе 0,2 мг / кг (группа смены фермента), с последующим проспективным наблюдением в течение 1 года. Оценивались клинические события (смерть, инфаркт миокарда, тяжелая аритмия, инсульт, прогрессирование до терминальной стадии почечной недостаточности); изменения функции сердца и почек, неврологический статус и симптомы, связанные с БФ (невропатическая боль, гипогидроз, диарея и тяжесть заболевания). В группе обычных доз функциональное состояние органов и симптомы, связанные с БФ, оставались стабильными. В группе ниженных доз отмечено уменьшение рассчитанной скорости клубочковой фильтрации примерно на 3 мл / мин / 1,73 м2 (p = 0,01), а в группе смены препарата – повышение медианного соотношения альбумин / креатинин со 114 (0–606) мг / г до 216 (0–2062) мг / г (p = 0,03). Кроме того, в группах сниженных доз и смены препарата обнаруживалось существенное повышение средних оценок по индексу оценки тяжести Майнц и частоты приступов боли, хронической боли, боли в желудочно-кишечном тракте и диареи. У пациентов, получавших агалсидазу бета в обычных дозах, наблюдали стабильное течение болезни, в то время как снижение доз привело к ухудшению функции почек и усугублению симптомов. Переход на агалсидазу альфа безопасен, однако возможны прогрессирование микроальбуминурии и усиление выраженности симптомов БФ

Interaction of hyperalgesia and sensory loss in complex regional pain syndrome type I (CRPS I)

Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group

Is there a role for melatonin in fibromyalgia?

Fibromyalgia, characterised by persistent pain, fatigue, sleep disturbance and cognitive dysfunction, is a central sensitivity syndrome that also involves abnormality in peripheral generators and in the hypothalamic pituitary adrenal axis. Heterogeneity of clinical expression of fibromyalgia with a multifactorial aetiology has made the development of effective therapeutic strategies challenging. Physiological properties of the neurohormone melatonin appear related to the symptom profile exhibited by patients with fibromyalgia and thus disturbance of it’s production would be compatible with the pathophysiology. Altered levels of melatonin have been observed in patients with fibromyalgia which are associated with lower secretion during dark hours and higher secretion during daytime. However, inconsistencies of available clinical evidence limit conclusion of a relationship between levels of melatonin and symptom profiles in patients with fibromyalgia. Administration of melatonin to patients with fibromyalgia has demonstrated suppression of many symptoms and an improved quality of life consistent with benefit as a therapy for the management of this condition. Further studies with larger samples, however, are required to explore the potential role of melatonin in the pathophysiology of fibromyalgia and determine the optimal dosing regimen of melatonin for the management of fibromyalgia