A parabrachial hub for the prioritization of survival behavior during pain
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ABSTRACT:
PROVIDER: PRJNA1285173 | ENA |
REPOSITORIES: ENA
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Project description:Long-term sustained pain following acute physical injury is a prominent feature of chronic pain conditions. Populations of neurons that rapidly respond to noxious stimuli or tissue damage have been identified in the spinal cord and several nuclei in the brain. Understanding the central mechanisms that signal ongoing sustained pain, including after tissue healing, remains a challenge. In this study, spatial transcriptomics, neural manipulations, activity recordings and computational modeling demonstrate that activity in an ensemble of anatomically and molecularly diverse parabrachial neurons that express the NPY Y1 receptor is elevated following injury and predicts functional coping behavior. Regardless of the injury type, hunger, thirst, or predator cues suppressed sustained pain by inhibiting PBN Y1R neurons via the release of NPY. Together, our results demonstrate an endogenous analgesic hub at pain-responsive parabrachial Y1R neurons
2025-07-06 | GSE301435 | GEO
Project description:We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful withinsubject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis.
2019-02-27 | GSE127208 | GEO
Project description:It remains unknown why upon similar acute/subacute painful conditions, pain persists in some individuals while in others it resolves. Genetic factors, mood, and functional alterations, particularly involving the mesolimbic network, appear to be key. In order to explore potential susceptibility/resistance factors, we screened a large population of rats with a peripheral neuropathy, and we isolated a small subset (<15%) that presented high thresholds (HT) to mechanical allodynia (reduced pain manifestation). The phenotype was sustained over 12 weeks and was associated with higher hedonic behavior when compared with low threshold subjects (LT). The nucleus accumbens (NAc) of HT and LT animals were isolated for proteomic analysis by Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS). Two hundred and sevety-nine proteins proteins displayed different expression between LT and HT animals/subjects.
2021-04-27 | PXD022478 | Pride
Project description:Formalin-evoked pain triggers sex-specific behavior and spinal immune response
| PRJNA940216 | ENA
Project description:Mounting evidence shows sex-related differences in the experience of pain with women suffering more from chronic pain than men. Yet, our understanding of the biological basis underlying those differences remains incomplete. Using an adapted model of formalin-induced chemical/inflammatory pain, we report here that in contrast to male mice, females distinctly display two types of nocifensive responses to formalin, distinguishable by the duration of the interphase. This could be explained by female gonadal hormones fluctuating across the estrus cycle, rather than by the transcriptional content of the dorsal horn of the spinal cord (DHSC). Additionally, deep RNA-sequencing of DHSC showed that formalin-evoked pain was accompanied by a male-preponderant enrichment in genes associated with the immune modulation of pain, revealing an unanticipated contribution of neutrophils. Taking advantage of the male-enriched transcript encoding the neutrophil associated protein Lipocalin 2 (Lcn2) and using flow cytometry, we confirmed that formalin triggered the recruitment of LCN2-expressing neutrophils in the pia mater of spinal meninges, preferentially in males. Our data consolidate the contribution of female estrus cycle to pain perception and provide evidence supporting a sex-specific immune regulation of formalin-evoked pain.
2023-06-21 | GSE226443 | GEO
Project description:Oral cancer patients experience pain at the site of the primary cancer. Patients with metastatic oral cancers report greater pain. Lack of pain identifies patients at low risk of metastasis with sensitivity = 0.94 and negative predictive value = 0.89. In the same cohort, sensitivity and negative predictive value of depth of invasion, currently the best predictor, were 0.95 and 0.92, respectively. Cancer pain is attributed to cancer-derived mediators that sensitize neurons and is associated with increased neuronal density. We hypothesized that pain mediators would be overexpressed in metastatic cancers from patients reporting high pain. We identified 40 genes overexpressed in metastatic cancers from patients reporting high pain (n=5) compared to N0 cancers (n=10) and normal tissue (n=5). The genes are enriched for functions in extracellular matrix organization and angiogenesis. They have oncogenic and neuronal functions and are reported in exosomes. Hierarchical clustering according to expression of neurotrophic and axon guidance genes also separated cancers according to pain and nodal status. Depletion of exosomes from cancer cell line supernatant reduced nociceptive behavior in a paw withdrawal assay, supporting a role for exosomes in cancer pain. The identified genes and exosomes are potential therapeutic targets for stopping cancer and attenuating pain.
2020-09-07 | GSE156178 | GEO
Project description:Mechanistic differences in neuropathic pain modalities revealed by correlating behavior with global expression profiling
| PRJNA399497 | ENA
Project description:Genomics of Pain - Resilience to Pain
| PRJNA498368 | ENA
Project description:Genomics of Pain - Resilience to Pain
| PRJNA498369 | ENA
Project description:Nociceptive response belongs to a basic animal behavior facilitating adaptability and survival upon external or internal stimuli. Fish, similarly to higher vertebrates, also possess nociceptive machinery. Current protocols involving procedures performed on adult zebrafish including heart cryoinjury do not, however, take into account the adverse effects including pain that may potentially arise from these methodologies. Here, we assess the effect of two analgesics, lidocaine and morphine, followed after the heart cryoinjury in zebrafish. Monitoring swimming behaviour together with histology and gene expression analysis at the single cell level using scRNA sequencing and RNAscope fluorescent in situ hybridization technology, we show morphine, but not lidocaine, significantly improves animal welfare 6 hours post-cryoinjury, without impairing heart regeneration process. Altogether, morphine should be considered as the analgesic of choice to reduce post-surgical pain in adult zebrafish.
2022-05-06 | GSE158919 | GEO