Pain
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Advancements in clinical science have shown the necessity for a paradigm shift away from a biomedical toward a biopsychosocial approach. Yet, the translation from clinical science into clinical practice is challenging. The aim of this study was to assess the short-term and mid-term changes in pain knowledge and attitudes and guideline-adherent recommendations of healthcare professionals (HCP) by means of an interdisciplinary training program (ITP) about chronic pain. ⋯ The knowledge and attitudes about pain scores improved at post-training (Δ = 9.04, 95% confidence interval 7.72-10.36) and at 6-month follow-up (Δ = 7.16, 95% confidence interval 5.73-8.59). After the training program, HCPs provided significantly more recommendations in accordance with clinical guidelines. Thus, an ITP can improve the biopsychosocial perspective of chronic pain management among HCPs in the short-term and mid-term.
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The development of nonopioid analgesics for the treatment of abdominal pain is a pressing clinical problem. To address this, we examined the expression of G i/o -coupled receptors, which typically inhibit nociceptor activation, in colonic sensory neurons. This led to the identification of the orphan receptor GPR35 as a visceral analgesic drug target because of its marked coexpression with transient receptor potential ankyrin 1 (TRPA1), a mediator of noxious mechanotransduction in the bowel. ⋯ Consistent with this mechanism of action, we confirmed that TRPA1-mediated colonic contractions evoked by SP release were abolished by CS pretreatment in a GPR35-dependent manner. Our data demonstrate that GPR35 agonists prevent the activation and sensitisation of colonic nociceptors through the inhibition of TRPA1-mediated SP release. These findings highlight the potential of GPR35 agonists to deliver nonopioid analgesia for the treatment of abdominal pain.
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Although the behavioral response to pain is complex and involves supraspinal processes, assessment of pain symptoms in animal models still mainly relies on reflex-based nociceptive tests, which do not account for the affective-motivational nor cognitive components of pain. We introduce a double avoidance place preference paradigm, an integrated testing procedure in freely moving rats that relies on the conflict between the avoidance of a dark compartment in which a thermal ramp is activated, and the escape towards an aversive brightly lit compartment. We were able to differentiate the first nociceptive threshold from the temperature of definitive escape from the dark compartment, conveying information on the adaptive behavior of animals. ⋯ In animals exhibiting hyperalgesia following intraplantar complete Freund adjuvant injection, escape thresholds were significantly higher than that of control animals, hinting at a maladaptive affective-motivational response to noxious stimulation. However, in cuff animals, we failed to reveal any hot nociceptive hypersensitivity, but animals exhibited a strong adaptive response to cold simulation upon reexposure. Overall, the proposed paradigm allows for an integrated cortical response leading to a proactive avoidance behavior, while fully complying with ethical standards in animal experimentation.
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Cell states are influenced by the regulation of gene expression orchestrated by transcription factors capable of binding to accessible DNA regions. To uncover if sex differences exist in chromatin accessibility in the human dorsal root ganglion (hDRG), where nociceptive neurons innervating the body are found, we performed bulk and spatial assays for transposase-accessible chromatin technology followed by sequencing (ATAC-seq) from organ donors without a history of chronic pain. Using bulk ATAC-seq, we detected abundant sex differences in the hDRG. ⋯ Strikingly, XIST, responsible for inactivating 1 X chromosome by compacting it and maintaining at the periphery of the nucleus, was found to be highly dispersed in female neuronal nuclei. This is likely related to the higher chromatin accessibility in X in female hDRG neurons observed using both ATAC-seq approaches. We have documented baseline epigenomic sex differences in the hDRG which provide important descriptive information to test future hypotheses.