Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Advances in understanding nociception and neuropathic pain.

ABSTRACT: Pain results from the activation of a subset of sensory neurones termed nociceptors and has evolved as a "detect and protect" mechanism. However, lesion or disease in the sensory system can result in neuropathic pain, which serves no protective function. Understanding how the sensory nervous system works and what changes occur in neuropathic pain are vital in identifying new therapeutic targets and developing novel analgesics. In recent years, technologies such as optogenetics and RNA-sequencing have been developed, which alongside the more traditional use of animal neuropathic pain models and insights from genetic variations in humans have enabled significant advances to be made in the mechanistic understanding of neuropathic pain.

SUBMITTER: St John Smith E

PROVIDER: S-EPMC5808094 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Advances in understanding nociception and neuropathic pain.

St John Smith Ewan E

Journal of neurology 20171014 2

Pain results from the activation of a subset of sensory neurones termed nociceptors and has evolved as a "detect and protect" mechanism. However, lesion or disease in the sensory system can result in neuropathic pain, which serves no protective function. Understanding how the sensory nervous system works and what changes occur in neuropathic pain are vital in identifying new therapeutic targets and developing novel analgesics. In recent years, technologies such as optogenetics and RNA-sequencing ...[more]

PMID: 29032407

Similar Datasets

Brain-Derived Neurotrophic Factor in the Mesolimbic Reward Circuitry Mediates Nociception in Chronic Neuropathic Pain.

Project description:BACKGROUND:The mesolimbic reward system plays a critical role in modulating nociception; however, its underlying molecular, cellular, and neural circuitry mechanisms remain unknown. METHODS:Chronic constrictive injury (CCI) of the sciatic nerve was used to model neuropathic pain. Projection-specific in vitro recordings in mouse brain slices and in vivo recordings from anesthetized animals were used to measure firing of dopaminergic neurons in the ventral tegmental area (VTA). The role of VTA-nucleus accumbens (NAc) circuitry in nociceptive regulation was assessed using optogenetic and pharmacological manipulations, and the underlying molecular mechanisms were investigated by Western blotting, enzyme-linked immunosorbent assays, and conditional knockdown techniques. RESULTS:c-Fos expression in and firing of contralateral VTA-NAc dopaminergic neurons were elevated in CCI mice, and optogenetic inhibition of these neurons reversed CCI-induced thermal hyperalgesia. CCI increased the expression of brain-derived neurotrophic factor (BDNF) protein but not messenger RNA in the contralateral NAc. This increase was reversed by pharmacological inhibition of VTA dopaminergic neuron activity, which induced an antinociceptive effect that was neutralized by injecting exogenous BDNF into the NAc. Moreover, inhibition of BDNF synthesis in the VTA with anisomycin or selective knockdown of BDNF in the VTA-NAc pathway was antinociceptive in CCI mice. CONCLUSIONS:These results reveal a novel mechanism of nociceptive modulation in the mesolimbic reward circuitry and provide new insight into the neural circuits involved in the processing of nociceptive information.

| S-EPMC5788809 | biostudies-literature

Recent advances in understanding and managing cancer pain.

Project description:Cancer pain remains a significant clinical problem worldwide. Causes of cancer pain are multifactorial and complex and are likely to vary with an array of tumor-related and host-related factors and processes. Pathophysiology is poorly understood; however, new laboratory research points to cross-talk between cancer cells and host's immune and neural systems as an important potential mechanism that may be broadly relevant to many cancer pain syndromes. Opioids remain the most effective pharmaceuticals used in the treatment of cancer pain. However, their role has been evolving due to emerging awareness of risks of chronic opioid therapy. Despite extensive research efforts, no new class of analgesics has been developed. However, many potential therapeutic targets that may lead to the establishment of new pharmaceuticals have been identified in recent years. It is also expected that the role of non-pharmacological modalities of treatment will grow in prominence. Specifically, neuromodulation, a rapidly expanding field, may play a major role in the treatment of neuropathic cancer pain provided that further technological progress permits the development of non-invasive and inexpensive neuromodulation techniques.

| S-EPMC5482325 | biostudies-other

Heritability of nociception IV: neuropathic pain assays are genetically distinct across methods of peripheral nerve injury.

Project description:Prior genetic correlation analysis of 22 heritable behavioral measures of nociception and hypersensitivity in the mouse identified 5 genetically distinct pain types. In the present study, we reanalyzed that dataset and included the results of an additional 9 assays of nociception and hypersensitivity, with the following goals: to replicate the previously identified 5 pain types; to test whether any of the newly added pain assays represent novel genetically distinct pain types; and to test the level of genetic relatedness among 9 commonly used neuropathic pain assays. Multivariate analysis of pairwise correlations between assays shows that the newly added zymosan-induced heat hypersensitivity assay does not conform to the 2 previously identified groups of heat hypersensitivity assays and cyclophosphamide-induced cystitis, the first organ-specific visceral pain model examined, is genetically distinct from other inflammatory assays. The 4 included mechanical hypersensitivity assays are genetically distinct and do not comprise a single pain type as previously reported. Among the 9 neuropathic pain assays including autotomy, chemotherapy, nerve ligation and spared nerve injury assays, at least 4 genetically distinct types of neuropathic sensory abnormalities were identified, corresponding to differences in nerve injury method. In addition, 2 itch assays and Comt genotype were compared to the expanded set of nociception and hypersensitivity assays. Comt genotype was strongly related only to spontaneous inflammatory nociception assays. These results indicate the priority for continued investigation of genetic mechanisms in several assays newly identified to represent genetically distinct pain types.

| S-EPMC3964153 | biostudies-literature

Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain.

Project description:BackgroundNeuropathic pain is characterized by hyperalgesia, allodynia and spontaneous pain. It often occurs as a result of injury to peripheral nerves, dorsal root ganglions (DRG), spinal cord, or brain. Recent studies have suggested that Toll-like receptor 4 (TLR4) might play a role in neuropathic pain.Methodology/principal findingsIn this study, we investigated the role of TLR4 in a rat chronic constriction injury (CCI) model and explored the feasibility of treating neuropathic pain by inhibiting TLR4. Our results demonstrated that intrathecal siRNA-mediated suppression of TLR4 attenuated CCI-induced mechanical allodynia and thermal hyperalgesia through inhibiting the activation of NF-kappaB p65 and production of proinflammatory cytokines (e.g., TNF-alpha and IL-1 beta).Conclusions/significanceThese findings suggest that suppression of TLR4 mediated by intrathecally administered siRNA may be a new strategy for the treatment of neuropathic pain.

| S-EPMC2920570 | biostudies-literature

Recent advances in understanding and managing phantom limb pain.

Project description:Post-amputation phantom limb pain (PLP) is highly prevalent and very difficult to treat. The high-prevalence, high-pain intensity levels, and decreased quality of life associated with PLP compel us to explore novel avenues to prevent, manage, and reverse this chronic pain condition. This narrative review focuses on recent advances in the treatment of PLP and reviews evidence of mechanism-based treatments from randomized controlled trials published over the past 5 years. We review recent evidence for the efficacy of targeted muscle reinnervation, repetitive transcranial magnetic stimulation, imaginal phantom limb exercises, mirror therapy, virtual and augmented reality, and eye movement desensitization and reprocessing therapy. The results indicate that not one of the above treatments is consistently better than a control condition. The challenge remains that there is little level 1 evidence of efficacy for PLP treatments and most treatment trials are underpowered (small sample sizes). The lack of efficacy likely speaks to the multiple mechanisms that contribute to PLP both between and within individuals who have sustained an amputation. Research approaches are called for to classify patients according to shared factors and evaluate treatment efficacy within classes. Subgroup analyses examining sex effects are recommended given the clear differences between males and females in pain mechanisms and outcomes. Use of novel data analytical approaches such as growth mixture modeling for multivariate latent classes may help to identify sub-clusters of patients with common outcome trajectories over time.

| S-EPMC6652103 | biostudies-literature

TNT model of neuropathic pain

Project description:In this experiment we compare the effect of tibial nerve transection on gene expression within the dorsal root ganglion (DRG) of rats.

2014-08-01 | E-MTAB-2260 | biostudies-arrayexpress

Neuropathic pain.

Project description:Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain.

| S-EPMC5371025 | biostudies-literature

Profiling Chung rat model for neuropathic pain

Project description:This program addresses the gene signature associated with DRG in the Chung rat model for neuropathic pain. The Chung neuropathic pain profiling data was analyzed by identifying genes that were up- and down-regulated at selected p value and fold change in DRG of the Sprague Dawley rats following spinal nerve ligation compared to the sham-operated controls.

2013-03-22 | E-GEOD-38038 | biostudies-arrayexpress

The α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain.

Project description:Background and purposeOrthosteric agonists and positive allosteric modulators (PAMs) of the α7 nicotinic ACh receptor (nAChR) represent novel therapeutic approaches for pain modulation. Moreover, compounds with dual function as allosteric agonists and PAMs, known as ago-PAMs, add further regulation of receptor function.Experimental approachInitial studies examined the α7 ago-PAM, GAT107, in the formalin, complete Freund's adjuvant (CFA), LPS inflammatory pain models, the chronic constriction injury neuropathic pain model and the tail flick and hot plate acute thermal nociceptive assays. Additional studies examined the locus of action of GAT107 and immunohistochemical markers in the dorsal horn of the spinal cord in the CFA model.Key resultsComplementary pharmacological and genetic approaches confirmed that the dose-dependent antinociceptive effects of GAT107 were mediated through α7 nAChR. However, GAT107 was inactive in the tail flick and hot plate assays. In addition, GAT107 blocked conditioned place aversion elicited by acetic acid injection. Furthermore, intrathecal, but not intraplantar, injections of GAT107 reversed nociception in the CFA model, suggesting a spinal component of action. Immunohistochemical evaluation revealed an increase in the expression of astrocyte-specific glial fibrillary acidic protein and phosphorylated p38MAPK within the spinal cords of mice treated with CFA, which was attenuated by intrathecal GAT107 treatment. Importantly, GAT107 did not elicit motor impairment and continued to produce antinociceptive effects after subchronic administration in both phases of the formalin test.Conclusions and implicationsCollectively, these results provide the first proof of principle that α7 ago-PAMs represent an effective pharmacological strategy for treating inflammatory and neuropathic pain.

| S-EPMC4959951 | biostudies-literature

Colored Pain Drawing as a Clinical Tool in Differentiating Neuropathic Pain from Non-Neuropathic Pain.

Project description:ObjectivesThis is a prospective, blinded, case-control study of patients with chronic pain using body diagrams and colored markers to show the distribution and quality of pain and sensory symptoms (aching, burning, tingling, numbness, and sensitivity to touch) experienced in affected body parts.MethodsTwo pain physicians, blinded to patients' clinical diagnoses, independently reviewed and classified each colored pain drawing (CPD) for presence of neuropathic pain (NeuP) vs. non-neuropathic pain (NoP). A clinical diagnosis (gold standard) of NeuP was made in 151 of 213 (70.9%) enrolled patients.ResultsCPD assessment at "first glance" by both examiners resulted in correctly categorizing 137 (64.3% by examiner 1) and 156 (73.2% by examiner 2) CPDs. Next, classification of CPDs by both physicians, using predefined criteria of spatial distribution and quality of pain-sensory symptoms, improved concordance to 212 of 213 CPDs (Kappa = 0.99). The diagnostic ability to correctly identify NeuP and NoP by both examiners increased to 171 (80.2%) CPDs, with 80.1% sensitivity and 80.6% specificity (Kappa = 0.56 [95% confidence interval: 0.44-0.68]). The severity scores for pain and sensory symptoms (burning, tingling, numbness, and sensitivity to touch) on the Neuropathic Pain Questionnaire were significantly elevated in NeuP vs. NoP (P < 0.001).ConclusionsThis study demonstrates good performance characteristics of CPDs in identifying patients with NeuP through the use of a simple and easy-to-apply classification scheme. We suggest use of CPDs as a bedside screening tool and as a method for phenotypic profiling of patients by the quality and distribution of pain and sensory symptoms.

| S-EPMC7971469 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data