Fusao Kato

Background: Patients' “pain attributions,” or their beliefs about chronic pain causes, critically affect pain experience and recovery, potentially modulating responses to analgesics and psychotropics. Since many pain‐mitigating drugs also impact psychological processes and brain functions underlying these attributions, such processes are relevant targets. The Chronic Pain Attribution Scale (CPAS) by Ashar et al. (2023) quantifies these beliefs. A Japanese version (CPAS‐J) is needed to assess this psychologically relevant construct in Japanese populations. This study aimed to develop and linguistically validate the CPAS‐J. Methods: The CPAS‐J was developed following International Society for Pharmacoeconomics and Outcomes Research guidelines, with permission from the original author. The process included forward translation by eight bilingual medical experts, reconciliation by a pain research team, back‐translation by an independent translator, review by the original author, and a final consensus discussion to establish the definitive CPAS‐J. Results: The linguistic validation identified challenges in distinguishing “cause” from “trigger” in Japanese. To enhance comprehensibility, the team combined “kikkake” (initiating factor) and “gen'in” (broader cause/origin). The finalized CPAS‐J assesses perceived causes of pain. Conclusions: The CPAS‐J was successfully developed through a rigorous process. This tool supports research on pain attributions in Japanese‐speaking populations and may improve our understanding of treatment responses by assessing a key psychological dimension of chronic pain that is linked to brain‐based processes.

Breathing behaviour is subject to emotional regulation, but the underlying mechanisms remain unclear. Here, we demonstrate a direct relationship between the central amygdala, a major output hub of the limbic system associated with emotional brain function, and the brainstem pre‐Bötzinger complex, which generates the fundamental rhythm and pattern for breathing. The connection between these two sites is monosynaptic and inhibitory, involving GABAergic central amygdala neurons whose axonal projections act predominantly via ionotropic GABA _A receptors to produce inhibitory postsynaptic currents in pre‐Bötzinger neurons. This pathway may provide a mechanism to inhibit breathing in the context of freezing to assess threats and plan defensive action. The existence of this pathway may further explain how epileptic seizures invading the amygdala cause long‐lasting apnea, which can be fatal. Although their ultimate importance awaits further behavioural tests, these results elucidate a link between emotional brain function and breathing, which underlies survival‐related behaviour in mammals and pertains to human anxiety disorders.

Itch is a protective/defensive function with divalent motivational drives. Itch itself elicits an unpleasant experience, which triggers the urge to scratch, relieving the itchiness. Still, it can also result in dissatisfaction when the scratch is too intense and painful or unsatisfactory due to insufficient scratch effect. Therefore, it is likely that the balance between the unpleasantness/pleasure and satisfaction/unsatisfaction associated with itch sensation and scratching behavior is determined by complex brain mechanisms. The physiological/pathological mechanisms underlying this balance remain largely elusive. To address this issue, we targeted the "reward center" of the brain, the nucleus accumbens (NAc), in which itch-responsive neurons have been found in rodents. We examined how neurons in the NAc are activated or suppressed during histamine-induced scratching behaviors in mice. The mice received an intradermal injection of histamine or saline at the neck, and the scratching number was analyzed by recording the movement of the bilateral hind limbs for about 45 min after injection. To experimentally manipulate the scratch efficacy in these histamine models, we compared histamine's behavioral and neuronal effects between mice with intact and clipped nails on the hind paws. As expected, the clipping of the hind limb nail increased the number of scratches after the histamine injection. In the brains of mice exhibiting scratching behaviors, we analyzed the expression of the c-fos gene (Fos) as a readout of an immediate activation of neurons during itch/scratch and dopamine receptors (Drd1 and Drd2) using multiplex single-molecule fluorescence in situ hybridization (RNAscope) in the NAc and surrounding structures. We performed a model-free analysis of gene expression in geometrically divided NAc subregions without assuming the conventional core–shell divisions. The results indicated that even within the NAc, multiple subregions responded differentially to various itch/scratch conditions. We also found different clusters with neurons showing similar or opposite changes in Fos expression and the correlation between scratch number and Fos expression in different itch/scratch conditions. These regional differences and clusters would provide a basis for the complex role of the NAc and surrounding structures in encoding the outcomes of scratching behavior and itchy sensations.

Introduction: Despite its recent reputation as prosocial neurohormone, the most important physiological role of oxytocin (OT) is stimulating uterine contractions. Though it is well known that plasma OT concentrations change drastically during delivery, it remains unexplored whether and how OT receptors in the maternal brain are activated. We examined whether the responses of cells in the central amygdala (CeA), an OT receptor-rich limbic site involved in pain and fear memory regulation, to exogenously applied OT analogue, Thr-Gly-OT (TGOT), vary depending on delivery. Methods: Intracellular Ca2+ dynamics of the CeA cells were visualized in brain slices from female rats at virgin (VG), during pregnancy term (PT) days 16–21, within 24 h after delivery (G0), and within 1–3 days after delivery (G3). The Ca2+ responses to 1 µM TGOT, 20 mM KCl (high K), and 300 µM ADP were compared. Results: We found that fraction of cells responding to TGOT, high K, and ADP differed significantly between the four delivery-associated terms. In particular, the fraction of cells responding to TGOT (TGOT responders) significantly increased from VG and PT at G0 and G3. Furthermore, the significant positive correlation between TGOT and high K response in TGOT and high K responders was reduced at G0, while that between TGOT and ADP responses in TGOT and ADP responders was increased at G0. Conclusion: These results indicate that the responses of CeA cells to an OT receptor agonist markedly change around delivery, which might play a role in controlling the labor-related pain and post-delivery emotional complications.