Project description:This clinical trial studies the effectiveness of a web-based cancer education tool called Helping Oncology Patients Explore Genomics (HOPE-Genomics) in improving patient knowledge of personal genomic testing results and cancer and genomics in general. HOPE-Genomics is a web-based education tool that teaches cancer/leukemia patients, and patients who may be at high-risk for developing cancer, about genomic testing and provide patients with information about their own genomic test results. The HOPE-Genomics tool may improve patient’s genomic knowledge and quality of patient-centered care. In addition, it may also improve education and care quality for future patients.
Project description:Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further unrelated individuals. Whole blood DNA methylation was characterized at 5.2 million loci by MeDIP-sequencing and assessed longitudinally to identify differentially methylated regions associated with high or low pain-sensitivity (pain-DMRs). Nine meta-analysis pain-DMRs show robust evidence for association (false discovery rate 5%) with the strongest signal in the pain gene TRPA1 (P=1.2M-CM-^W10-13). Several pain-DMRs show longitudinal stability consistent with susceptibility effects, have similar methylation levels in brain, and altered expression in skin. Our approach identifies epigenetic changes in both novel and established candidate genes that provide molecular insights into pain and may generalize to other complex traits. MeDIP-sequencing in 100 individulas using a 2 stage design: paired-end MeDIP-seq in 50 monozygotic twins and single-end MeDIP-seq in 50 unrelated individuals.
Project description:We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia a prominent symptom of chronic pain. Expression genetics identifies a role for the Chrna6 (alpha 6-nicotinic receptor) gene in pain in mice and humans. Dorsal root ganglion tissue across multiple inbred mouse strains, both male and female
Project description:Pain experienced within a social context impacts infant neurobehavioral responses and initiates an altered developmental trajectory of pain and affect processing that diverges from experiencing pain alone. We used microarrays to detail the gene expression following pain with and without the mother at different preweaning ages
Project description:We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia a prominent symptom of chronic pain. Expression genetics identifies a role for the Chrna6 (alpha 6-nicotinic receptor) gene in pain in mice and humans.
Project description:Six different mouse pain models were studied: (1) tumour-injection model for bone cancer pain; (2) partial sciatic nerve ligation (PSL) for neuropathic pain; (3) mechanical joint loading for osteoarthritis pain; (4) oxaliplatin-induced painful neuropathy for chemotherapy-induced pain; (5) hyperalgesic priming model for chronic muscle pain; and (6) complete Freund’s adjuvant (CFA)-injection for inflammatory pain. Transcriptomic microarray analyses were performed using RNA isolated from dorsal root ganglia.
Project description:Despite widespread use of experimental acute pain models to mimic chronic pathologies, little exploration has been undertaken on the acute pain proteome in humans. We re-solved to explore molecular alterations evoked by acute bouts of hypertonic saline (HS) induced muscle pain and map the spread of evoked mechanical hyperalgesia. This study used a 2-cohort design in healthy human participants. Cohort one (n=16) underwent in-termittent blood sampling concurrent with intramuscular HS (5%) infusion to allow for the discovery of the proteomic and cytokine profile of acute muscle pain. Cohort two (n=10) underwent bilateral sensory testing during HS infusion, to map the spread of evoked mechanical hyperalgesia. Molecular analysis in cohort one revealed a diffuse ar-ray of proteins and cytokines showing altered expression in response to acute muscle pain. Particularly these alterations were linked to metabolism and immune response pathways suggestive of systemic effects of acute pain. Intriguingly, cohort two revealed a significant mechanical hyperalgesia which emerged in a diffuse pattern over the ipsilat-eral limb to HS-infusion. However, despite evidence of systemic molecular alterations, no such mechanical hypersensitivity was observed in the contralateral limb. This study demonstrates systemic molecular alterations resultant from acute bouts of HS-induced muscle pain with accompanying sensory interactions.
Project description:Chronic neuropathic pain is widespread, but individual diagnostic biomarkers are unknown and primate specificity hampers rodent validation tests. Here, we report that microRNA (miR)-sequencing of blood leukocytes from 250 multi-centre pain patients revealed complex regional pain syndrome (CRPS)-related increases in the pain-related microRNA (miR)-21-5p and decreases in the cholinergic-targeted miR-335-5p. Both these miRs were similarly modified in dorsal root ganglia of nerve-injured mice, where long RNA-sequencing detected pain-associated elevation of neurogenesis and inflammation-related transcripts. Moreover, either genomic ablation or intrathecal antisense oligonucleotide neuro-suppression of miR-21a-5p, but not genetic debilitation of B7-H1 lymphocytes alleviated murine pain responses while reducing cellular pathways that are induced in patients’ leukocytes; and a cooperative leukocyte ‘signature’ of 12 miRs including miR-21a-5p and -335-5p predicted 96% of CRPS symptoms severity. Our findings implicate cholinergic-suppressible neuro-inflammation processes in chronic acute pain, suggest pathway-based cooperative validation tests and open unprecedented options for mechanistic studies of chronic pain disorders.