Pain
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Impaired selective fear learning has been advanced as a core mechanism involved in excessive spreading of protective responses such as pain-related fear and avoidance leading to disability in chronic pain conditions. Using the litmus test for selective learning effects, the blocking procedure, we tested the hypothesis that patients with fibromyalgia (FM) show less selective threat learning than healthy controls (HCs). We introduce a novel selective learning task based around a clinical diary scenario. ⋯ Simultaneously, a novel situation was introduced and also followed by "pain" (B+). Within-group comparisons showed blocking (ie, significant difference between B and X) in the HCs, but not in the patients with FM. This study is the first in directly assessing differences in selective learning between patients with FM and HCs using a blocking procedure.
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Individual differences in sensitivity to pain are large and have clinical and scientific importance. Although heavily influenced by situational factors, they also relate to genetic factors and psychological traits, and are reflected by differences in functional activation in pain-related brain regions. Here, we used voxel-based morphometry to investigate if individual pain sensitivity is related to local gray matter volumes. ⋯ Alternatively, associations of PSQ scores with the parahippocampal and fusiform gray matter could relate to the visual imagination of painful situations required by the PSQ, not to pain sensitivity itself. Regarding PPTs, the present data obtained in a large sample strongly suggest an absence of associations of this parameter with gray matter volume. In conclusion, the present results argue against a strong association between pain sensitivity and local gray matter volumes.
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Proteases and protease-activated receptors (PARs) are major mediators involved in irritable bowel syndrome (IBS). Our objectives were to decipher the expression and functionality (calcium signaling) of PARs in human dorsal root ganglia (DRG) neurons and to define mechanisms involved in human sensory neuron signaling by IBS patient mediators. Human thoracic DRG were obtained from the national disease resource interchange. ⋯ Thrombin increased calcium flux, which was inhibited by a PAR1 antagonist and increased by a PAR4 antagonist. Supernatants from colonic biopsies of patients with IBS induced calcium flux in human sensory neurons compared with healthy controls, and this induction was reversed by a PAR1 antagonist. Taken together, our results highlight that PAR1 antagonism should be investigated as a new therapeutic target for IBS symptoms.
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Comparative Study
Comparative transcriptome profiling of the human and mouse dorsal root ganglia: an RNA-seq-based resource for pain and sensory neuroscience research.
Molecular neurobiological insight into human nervous tissues is needed to generate next-generation therapeutics for neurological disorders such as chronic pain. We obtained human dorsal root ganglia (hDRG) samples from organ donors and performed RNA-sequencing (RNA-seq) to study the hDRG transcriptional landscape, systematically comparing it with publicly available data from a variety of human and orthologous mouse tissues, including mouse DRG (mDRG). We characterized the hDRG transcriptional profile in terms of tissue-restricted gene coexpression patterns and putative transcriptional regulators, and formulated an information-theoretic framework to quantify DRG enrichment. ⋯ Comparison of hDRG and tibial nerve transcriptomes suggests trafficking of neuronal mRNA to axons in adult hDRG, and are consistent with studies of axonal transport in rodent sensory neurons. We present our work as an online, searchable repository (https://www.utdallas.edu/bbs/painneurosciencelab/sensoryomics/drgtxome), creating a valuable resource for the community. Our analyses provide insight into DRG biology for guiding development of novel therapeutics and a blueprint for cross-species transcriptomic analyses.
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Heat pain and its modulation by capsaicin varies among subjects in experimental and clinical settings. A plausible cause is a genetic component, of which TRPV1 ion channels, by their response to both heat and capsaicin, are primary candidates. However, TRPA1 channels can heterodimerize with TRPV1 channels and carry genetic variants reported to modulate heat pain sensitivity. ⋯ Of note, TRPA1 variants were more important for correct phenotype group association than TRPV1 variants. This indicates a role of the TRPA1 and TRPV1 next-generation sequencing-based genetic pattern in the modulation of the individual response to heat-related pain phenotypes. When considering earlier evidence that topical capsaicin can induce neuropathy-like quantitative sensory testing patterns in healthy subjects, implications for future analgesic treatments with transient receptor potential inhibitors arise.