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Calcitonin gene-related peptide levels in tear fluid are elevated in migraine patients compared to healthy controls.

Calcitonin gene-related peptide (CGRP) released from trigeminal nerve fibres indicates trigeminal activation and has a key role in migraine pathophysiology. The trigeminal nerve directly innervates the eye. Therefore, in this study, we compared Calcitonin gene-related peptide in tear fluid of migraine patients and healthy controls.

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The role of perceived stress and life stressors in the development of chronic musculoskeletal pain disorders: a systematic review.

The aetiological role of work-related psychological stress in the development of musculoskeletal pain disorders (MDs) has been systematically investigated. Less clear however, is the role of perceived stress and life stressors. This review aimed to assess the evidence for an aetiological role of perceived stress and life stressors in the development of chronic MDs. Database searches were conducted to identify prospective longitudinal studies that assessed perceived stress and life stressors in individuals without, or in the first 6 weeks of musculoskeletal pain. The primary outcome was the development of a chronic MD. Methodological quality was investigated using an adapted version of the Quality Assessment Tool for Observational Cohort studies and Cross-Sectional studies, and the strength of evidence using the GRADE approach. Seven studies were included representing data from six independent cohorts. There was some evidence to support the aetiological role of perceived stress and life stressors in the development of arthritis (low quality) and chronic spinal pain (low quality). The limited number of studies, the poor quality of the evidence and heterogeneity of stress measures used across studies suggest that further high quality prospective studies are required to clarify the role of perceived stress and life stressors in the development of chronic MDs. PROSPERO: CRD42017059949 Perspective: This review summarizes and critically appraises the evidence for the aetiological role of perceived stress and life stressors in the development of chronic MDs. The limited number of studies, the low quality of the evidence and heterogeneity across studies suggest that further research is needed on perceived stress and life stressors in MDs.

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Kinins and their B1 and B2 receptors are involved in fibromyalgia-like pain symptoms in mice.

Fibromyalgia is a disease characterised as generalised chronic primary pain that causes functional disability and a reduction in patients' quality of life, without specific pathophysiology or appropriate treatment. Previous studies have shown that kinins and their B and B receptors contribute to chronic painful conditions. Thus, we investigated the involvement of kinins and their B and B receptors in a fibromyalgia-like pain model induced by reserpine in mice. Nociceptive parameters (mechanical allodynia, cold sensitivity and overt nociception) and behaviours of burrowing, thigmotaxis, and forced swimming were evaluated after reserpine administration in mice. The role of kinin B and B receptors was investigated using knockout mice or pharmacological antagonism. The protein expression of kinin B and B receptors and the levels of bradykinin and monoamines were measured in the sciatic nerve, spinal cord and cerebral cortex of the animals. Knockout mice for the kinin B and B receptor reduced reserpine-induced mechanical allodynia. Antagonism of B and B receptors also reduced mechanical allodynia, cold sensitivity and overt nociception reserpine-induced. Reserpine altered thigmotaxis, forced swimming and burrowing behaviour in the animals; with the latter being reversed by antagonism of kinin B receptor. Moreover, reserpine increased the protein expression of kinin B and B receptors and levels of kinin, as well as reduced the levels of monoamines in peripheral and central structures. Kinins and its B and B receptors are involved in fibromyalgia-like pain symptoms. B or B receptors might represent a potential target for the relief of fibromyalgia-like pain symptoms.

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Imaging spinal cord activity in behaving animals.

The spinal cord is the primary neurological link between the brain and peripheral organs. How important it is in everyday life is apparent in patients with spinal cord injury or motoneuron disease, who have dramatically reduced musculoskeletal control or capacity to sense their environment. Despite its crucial role in sensory and motor processing little is known about the cellular and molecular signaling events that underlie spinal cord function under naturalistic conditions. While genetic, electrophysiological, pharmacological, and circuit tracing studies have revealed important roles for different molecularly defined neurons, these approaches insufficiently describe the moment-to-moment neuronal and non-neuronal activity patterns that underlie sensory-guided motor behaviors in health and disease. The recent development of imaging methods for real-time interrogation of cellular activity in the spinal cord of behaving mice has removed longstanding technical obstacles to spinal cord research and allowed new insight into how different cell types encode sensory information from mechanoreceptors and nociceptors in the skin. Here, we review the current state-of-the-art in interrogating cellular and microcircuit function in the spinal cord of behaving mammals and discuss current opportunities and technological challenges.

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Beyond pain: can antidepressants improve depressive symptoms and quality of life in patients with neuropathic pain? A systematic review and meta-analysis.

Neuropathic pain can be a predictor of severe emotional distress, up to full blown depressive states. In these patients, it is important to move beyond the sole treatment of pain, in order to recognize depressive symptoms, and to ultimately improve the quality of life.We systematically searched for published and unpublished clinical trials assessing the efficacy and tolerability of antidepressants versus placebo on depression, anxiety and quality of life in patients with neuropathic pain, and pooled data in a meta-analysis.A total of 37 studies fulfilled eligibility criteria and 32 provided data for meta-analysis. Antidepressants were more effective than placebo in improving depressive symptoms (standardized mean difference -0.11; 95% confidence interval -0.20 to -0.02), although the magnitude of effect was small, with a number-needed-to-treat of 24. No significant difference emerged between antidepressants and placebo in reducing anxiety. Quality of life appeared improved in patients on antidepressants, as did pain. Acceptability and tolerability were higher in patients on placebo.To our knowledge, this is the first meta-analysis specifically focusing on the effect of antidepressants on psychiatric symptoms and quality of life in patients with neuropathic pain. Our findings suggest that, despite their potential benefit in patients with neuropathic pain, antidepressants should be prescribed with particular care, as they might be less tolerable in such a fragile population. However, our findings warrant further research to explore how a correct use of antidepressants can help patients to cope with the consequences of neuropathic pain on their psychosocial health and quality of life.

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Feasibility of a traditional and teletreatment approach to mirror therapy in patients with phantom limb pain: a process evaluation performed alongside a randomized controlled trial.

To evaluate the delivery, acceptance and experiences regarding a traditional and teletreatment approach to mirror therapy as delivered in a randomized controlled trial.

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Spouse and Patient Beliefs and Perceptions About Chronic Pain: Effects on Couple Interactions and Patient Pain Behavior.

Patient beliefs and perceptions about the causes and meaning of their chronic pain are related to their psychosocial functioning. Beliefs and perceptions about chronic pain held by spouses may also be related to patient functioning. We used a laboratory procedure to evaluate whether spouse beliefs about and perceptions of chronic pain were related to spouse negative responses toward patients with chronic low back pain during a conflictual discussion and to their attributions about patient pain behavior during a subsequent pain-induction task. Patients (n = 71) and their spouses (n = 71) participated in a 10-minute discussion followed by the patient undergoing a 10-minute structured pain behavior task. Findings were that a) spouse perceptions that patient's pain was a mystery were significantly related to greater patient perceived spouse critical/invalidating responses toward the patient during the discussion; and b) spouse perceptions that patient's pain was a mystery were related to internal and negative attributions spouses made while observing patients display pain behaviors during the structured pain behavior task. Inasmuch as both spouse critical/invalidating speech toward patients and negative attributions regarding the cause of patient behavior are related to poor patient functioning, spouse uncertainty about the source and potential legitimacy of their partner's pain may play crucial roles in affecting patient well-being. PERSPECTIVE: Spouse beliefs about and perceptions of patient chronic pain were related to spouse behavior toward patients during a discussion and to attributions explaining patient pain during physical activity. If spouse confusion and doubt about patient pain is related to negative behavior and attributions, then modifying these perceptions may be a fundamental intervention target.

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Measurement of chronic pain in companion animals: Priorities for future research and development based on discussions from the Pain in Animals Workshop (PAW) 2017.

The estimation of long-standing pain in companion animals through the measurement of different dimensions impacted by pain is a fundamental requirement if pain management, and pain therapeutic development, are to advance. Although pain management in veterinary medicine has advanced considerably in the last 20 years, there is much critical work to do in the area of measurement of chronic pain. To date, most work has centered on musculoskeletal pain, and has been focused around the measurement of limb use and the development of owner-completed questionnaires, or clinical metrology instruments (CMI). Recent areas of research have extended to developing measures of activity, sensory function (quantitative sensory testing; nociceptive withdrawal reflexes), and quality of life (QoL). Across all these areas, more data on validity are needed, and studies should be extended to other painful disease states. By necessity, assessing measurement tools requires testing in field studies, which incur considerable time and expense. Facilitating these studies could be optimized with a collaborative (industry, academia and private practice) approach, and the utility of the information produced from all field studies would be enhanced by full and transparent reporting and data sharing, including data already generated by industry in the form of studies submitted to the regulatory authorities.

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Towards an Effective and Safe Treatment of Inflammatory Pain: A Delphi-Guided Expert Consensus.

The clinical management of inflammatory pain requires an optimal balance between effective analgesia and associated safety risks. To date, mechanisms associated with inflammatory pain are not completely understood because of their complex nature and the involvement of both peripheral and central mechanisms. This Expert Consensus document is intended to update clinicians about evolving areas of clinical practice and/or available treatment options for the management of patients with inflammatory pain.

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Extensor/flexor ratio of neck muscle strength and electromyographic activity of individuals with migraine: a cross-sectional study.

Neck pain is considered a common characteristic of migraine attacks. The relationship between neck pain and migraine can be explained by central sensitization of the trigeminocervical complex, where superior cervical afferents and the trigeminal nerve converge. However, few studies have evaluated motor control of cervical muscles in individuals with migraine. Thus, the purpose of the present study was to determine the extensor/flexor ratio of neck muscle strength and electromyographic activity during a test of maximal voluntary isometric contraction and craniocervical flexion in individuals with migraine and individuals without history of migraine or other headaches.

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