Dataset Information

Insights into the regulation of chemokine receptors by molecular signaling pathways: functional roles in neuropathic pain.

ABSTRACT: Inflammation plays a central role in the manner that the nervous system responds to injury. These effects include vasodilatation, increased vascular permeability, plasma extravasation, cell migration, and pain. Extracellular signals associated with inflammation may also lead to increased levels of pro-nociceptive chemokines/receptors that directly contribute to persistent or chronic pain behavior. To date, research focused on improving the treatment of chronic pain has largely ignored the role of inflammation-associated transcription factors such as nuclear transcription factor in activated T cells (NFAT). Herein we discuss the idea that activation of this transcription factor may be responsible for the production of chemokines receptors in both neuronal and non-neuronal cells of the peripheral nervous system. Taken together, a better understanding of the transcription of these pro-nociceptive genes may lead to the development of novel analgesic targets.

SUBMITTER: White FA

PROVIDER: S-EPMC2897965 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Insights into the regulation of chemokine receptors by molecular signaling pathways: functional roles in neuropathic pain.

White Fletcher A FA Miller Richard J RJ

Brain, behavior, and immunity 20100327 6

Inflammation plays a central role in the manner that the nervous system responds to injury. These effects include vasodilatation, increased vascular permeability, plasma extravasation, cell migration, and pain. Extracellular signals associated with inflammation may also lead to increased levels of pro-nociceptive chemokines/receptors that directly contribute to persistent or chronic pain behavior. To date, research focused on improving the treatment of chronic pain has largely ignored the role o ...[more]

PMID: 20347955

Similar Datasets

Project description:PURPOSE:This is a comprehensive review of the current literature on central neuropathic pain mechanisms that is secondary to spinal cord injury. It reviews recent and seminal findings on the pathophysiology, diagnosis, and treatment and compares treatment options and recommendations. RECENT FINDINGS:Neuropathic pain (NP) is a common complication of spinal cord injury (SCI). Chronicity of NP is attributed to increased abundance of inflammatory mediators and ion channel dysfunction leading to afferent nerve sensitization; nerve damage and nerve-glia cross talk have also been implicated. Conventional treatment is medical and has had limited success. Recent studies have made headway in identifying novel biomarkers, including microRNA and psychosocial attributes that can predict progress from SCI to chronic NP (CNP). Recent advances have provided evidence of efficacy for two promising drugs. Baclofen was able to provide good, long-lasting pain relief. Ziconotide, a voltage-gated calcium channel blocker, was studied in a small trial and was able to provide good analgesia in most participants. However, several participants had to be withdrawn because of worrisome creatine phosphokinase (CPK) elevations, and further studies are required to define its safety profile. Non-medical interventions include brain sensitization and biofeedback techniques. These methods have recently had encouraging results, albeit preliminary. Case reports of non-conventional techniques, such as hypnosis, were also reported. CNP is a common complication of SCI and is a prevalent disorder with significant morbidity and disability. Conventional medical treatment is limited in efficacy. Recent studies identified baclofen and ziconotide as possible new therapies, alongside non-medical interventions. Further research into the pathophysiology is required to identify further therapy candidates. A multidisciplinary approach, including psychosocial support, medical and non-medical interventions, is likely needed to achieve therapeutic effects in this difficult to treat syndrome.

Project description:Persistent postsurgical neuropathic pain (PPSNP) can occur after intraoperative damage to somatosensory nerves, with a prevalence of 29-57% in breast cancer surgery. Proteomics is an active research field in neuropathic pain and the first results support its utility for establishing diagnoses or finding therapy strategies. 57 women (30 non-PPSNP/27 PPSNP) who had experienced a surgeon-verified intercostobrachial nerve injury during breast cancer surgery, were examined for patterns in 74 serum proteomic markers that allowed discrimination between subgroups with or without PPSNP. Serum samples were obtained both before and after surgery. Unsupervised data analyses, including principal component analysis and self-organizing maps of artificial neurons, revealed patterns that supported a data structure consistent with pain-related subgroup (non-PPSPN vs. PPSNP) separation. Subsequent supervised machine learning-based analyses revealed 19 proteins (CD244, SIRT2, CCL28, CXCL9, CCL20, CCL3, IL.10RA, MCP.1, TRAIL, CCL25, IL10, uPA, CCL4, DNER, STAMPB, CCL23, CST5, CCL11, FGF.23) that were informative for subgroup separation. In cross-validated training and testing of six different machine-learned algorithms, subgroup assignment was significantly better than chance, whereas this was not possible when training the algorithms with randomly permuted data or with the protein markers not selected. In particular, sirtuin 2 emerged as a key protein, presenting both before and after breast cancer treatments in the PPSNP compared with the non-PPSNP subgroup. The identified proteins play important roles in immune processes such as cell migration, chemotaxis, and cytokine-signaling. They also have considerable overlap with currently known targets of approved or investigational drugs. Taken together, several lines of unsupervised and supervised analyses pointed to structures in serum proteomics data, obtained before and after breast cancer surgery, that relate to neuroinflammatory processes associated with the development of neuropathic pain after an intraoperative nerve lesion.

Dataset Information

Insights into the regulation of chemokine receptors by molecular signaling pathways: functional roles in neuropathic pain.

Publications

Insights into the regulation of chemokine receptors by molecular signaling pathways: functional roles in neuropathic pain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets