Clinical symptoms in fibromyalgia are associated to catechol-O-methyltransferase (COMT) gene Val158Met polymorphism

Abstract

1.?Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. The aim of this study was to explore the frequency and clinical significance of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism in a large cohort of Turkish patients with FMS.

2.?The study included 379 FMS patients and 290 controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses.

3.?The genotype frequencies of Val158Met polymorphism showed a small difference between FMS patients and healthy controls (p?=?0.047), however, the Met/Met genotype was significantly higher in FMS patients than healthy controls (p?=?0.016). No difference was observed for allele frequencies between two groups. Stratification analysis according to clinical features for this disease reveals that weight, FMS Impact Questionnaire score, algometry and Raynaud’s syndrome, were detected to have statistically significant associations with Val158Met polymorphism (p?=?0.037, p?=?0.042, p?=?0.039 and p?=?0.033, respectively). Pain sensitivity, measured by algometry, was statistically higher in patients with Met/Met genotype than the patients with Val/Val and Val/Met genotypes (p?=?0.017).

4.?The results of this study suggested that COMT gene Val158Met polymorphism is positively associated with FMS and play a relevant role in the clinical symptoms of the disease.     

Chronic,Intractable, Benign Pain: A Syndrome and its Treatment with Intensive Short-term Group Psychotherapy

Abstract

There is sufficient reason to classify some ongoing pain problems as syndromes. Patients who suffer with chronic, intractable, benign pain syndromes (CIBPS) have truly functional biopsychosocial disorders. There is no longer any current pathophysiology operative, and the pain syndrome persists with its psychosocially perpetuating and disrupting features. An intense group psychotherapy approach in the therapeutic milieu of a medical-surgical setting fosters and evokes affect expression and understanding. This encourages the formation of cognitive patterns that are therapeutically useful in that they extend coping abilities and, hence, diminish the pain and suffering experience and life problems attendant to it.     

Pain after Discontinuation of Morphine Treatment Is Associated with Synaptic Increase of GluA4-Containing AMPAR in the Dorsal Horn of the Spinal Cord

Withdrawal from prescribed opioids results in increased pain sensitivity, which prolongs the treatment. This pain sensitivity is attributed to neuroplastic changes that converge at the spinal cord dorsal horn. We have recently reported that repeated morphine administration triggers an insertion of GluA2-lacking (Ca²⁺-permeable) α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) in the hippocampus. This finding together with the reported involvement of AMPAR in the mechanisms underlying inflammatory pain led us to hypothesize a role for spinal AMPAR in opioid-induced pain behavior. Mice treated with escalating doses of morphine showed hypersensitivity to mechanical stimulation. Intrathecal administration of a Ca²⁺-permeable AMPAR selective blocker disrupted morphine-induced mechanical sensitivity. Analysis of the expression and phosphorylation levels of AMPAR subunits (GluA1/2/3/4) in homogenates and in postsynaptic density fractions from spinal cord dorsal horns showed an increase in GluA4 expression and phosphorylation in the postsynaptic density after morphine. Co-immunoprecipitation analyses suggested an increase in GluA4 homomers (Ca²⁺-permeable AMPAR) and immunohistochemical staining localized the increase in GluA4 levels in laminae III–V. The excitatory postsynaptic currents (EPSCs) recorded in laminae III–V showed enhanced sensitivity to Ca²⁺-permeable AMPAR blockers in morphine-treated mice. Furthermore, current–voltage relationships of AMPAR-mediated EPSCs showed that rectification index (an indicator of Ca²⁺-permeable AMPAR contribution) is increased in morphine-treated but not in saline-treated mice. These effects could be reversed by infusion of GluA4 antibody through patch pipette. This is the first direct evidence for a role of GluA4-containing AMPAR in morphine-induced pain and highlights spinal GluA4-containing AMPAR as targets to prevent the morphine-induced pain sensitivity.     

Anterior abdominal wall ‘peritoneal recess’: cause for pseudoherniation of small bowel resulting in chronic abdominal pain

A middle-aged patient presented with intermittent chronic abdominal pain without any obvious cause. Computed tomography detected a hernia (presumed to be the cause of the patient’s symptoms) without any obvious lump on examination. A laparoscopy was performed to repair the hernia. This revealed a left-sided unilateral ‘peritoneal recess’ at the level of the arcuate line extending medial to the linea semilunaris. No extraperitoneal sac or defect was noted in the rectus sheath or in the muscle, nor were any contents present in the recess at the time of the laparoscopy. We believe the bowel was being trapped intermittently in this space, causing the abdominal symptoms.     

神经血管治疗仪联合前列地尔等治疗糖尿病足疗效观察

目的探讨神经血管治疗仪联合前列地尔等治疗糖尿病足的临床疗效。方法将70例糖尿病足患者随机分为2组,每组各35例。试验组给予神经血管治疗仪、红外线照射疼痛治疗仪联合前列地尔治疗,并给予无菌换药;对照组仅给予前列地尔针剂等药物和无菌换药治疗。观察两组的临床疗效、平均住院时间、症状体征消失时间、ABI指标水平。结果试验组的总有效率显著高于对照组(P<0.05);平均住院时间和症状体征消失时间显著短于对照组(P<0.05);ABI指标水平显著优于对照组(P<0.05)。结论神经血管治疗仪、红外线照射疼痛治疗仪联合前列地尔、无菌换药治疗糖尿病足临床疗效显著,值得临床推广应用。     

Temporomandibular disorder in a patient with pseudoxanthoma elasticum: a case report and review

Pseudoxanthoma elasticum (PXE) is a disorder characterized by progressive degeneration of elastic fibers and ectopic mineralization. Cutaneous manifestations are a hallmark of this disease and organs that may be affected by the disease process include cardiovascular, central nervous system, ocular and gastrointestinal systems. Oral manifestations of PXE have been previously reported as intramucosal nodules observed on various intraoral surfaces. We present a case of a 46‐year‐old female with PXE diagnosed with temporomandibular disorder (TMD). To our knowledge, this is the first report of a patient with TMD coexisting with PXE in the scientific literature.     

肝动脉化疗栓塞术患者的多模式疼痛管理

目的评价多模式疼痛管理方案应用于肝动脉化疗栓塞术患者的效果。方法将166例肝动脉化疗栓塞术患者随机分为对照组80例和干预组86例,对照组采用传统疼痛管理策略,干预组采用多模式疼痛管理策略,包括建立医生、护士、药师及疼痛治疗师多学科团队,实施多模式镇痛知识宣教、超前非甾体抗炎药镇痛、局部浸润渗透、静脉自控镇痛泵、疼痛分级护理等措施。结果干预组术后24h内疼痛严重程度、不良反应(恶心呕吐、便秘腹胀)发生率及睡眠质量显著优于对照组(P0.05,P0.01)。结论多模式疼痛管理方案可有效控制肝动脉化疗栓塞术患者术后疼痛,有利于促进术后恢复。     

Osseous metastases: drugs that enhance bone integrity and prevent adverse skeletal events

More than 400,000 cancer patients in the USA contend with bone metastases on an annual basis. These patients often suffer pain, a decline in quality of life, and a shortened survival. As a result, over the past several years, efforts to enhance bone integrity in patients with osseus metastases have become a major research priority. This review discusses the evolving role of bisphosphonates and their side effects, highlights other pharmacological interventions aimed at enhancing bone integrity, and reviews other pragmatic approaches to prevent worsening pain and fractures, as derived from a single institution case series of patients with problematic rib metastases.     

Recent advances towards the discovery of ORL-1 receptor agonists and antagonists

Since their discovery a decade ago, remarkable progress has been made toward understanding the biological function and significance of the opioid receptor-like-1 (ORL-1) receptor and its endogenous peptide ligand, nociceptin. The human nociceptin receptor, herein referred to as ORL-1, but also known as OP4 (the fourth member of opioid peptide receptor family) or nociceptin/orphanin FQ peptide (NOP) receptor, was first identified as an orphan opioid receptor with close homology to the classical μ-, κ-, and δ-opioid receptors. ORL-1 does not bind endogenous ligands of the other opioid receptors with high affinity, but instead prefers the 17 amino acid peptide nociceptin. The obvious homologies of ORL-1 to opioid receptors, and its ligand nociceptin to opioid peptide ligands, led to a period of intense investigation that resulted in a number of significant reports describing the biology of the receptor and ligand. The emerging pharmacological evidence from these reports suggests that ORL-1 agonists may be clinically useful for treatment of stress, anxiety, substance abuse (opioid and alcohol), anorexia, cachexia, cough, asthma, and possibly neuropathic pain/allodynia. The peripheral effects of nociceptin suggest that agonists may have utility in the treatment of gastrointestinal motility disorders, water retention, and hypertension. ORL-1 antagonists may be useful in enhancing cognitive function and treating locomotor disorders such as Parkinsonism. In addition to research into the fundamental biology of ORL-1 and nociceptin, noteworthy advances have been made in the discovery of new peptide and non-peptide agonists and antagonists of the ORL-1 receptor leading to a better understanding of its involvement in a variety of biological processes. This review highlights the rationale for the development of ORL-1 ligands and recent progress made by different research groups towards the development of peptidic and non-peptidic ORL-1 agonists or antagonists over the last four years. To add perspective on the commercial potential of this research area, the development status of advanced new molecules is addressed together with any pharmacological characterisation of these entities.