生理学报最新文献

Pseudounipolar neurons in the dorsal root ganglia (DRG), as the central nodes of primary sensory afferents, possess a distinctive T-junction that is not merely a morphological peculiarity but also performs complex roles in rapid, multiplexed shunting and regulation of sensory signals. This specialized geometry enables separation, filtering, and feedback regulation of neuronal signals, thereby coordinating peripheral and central responses at multiple levels. Recent advances, including spatial transcriptomics, single-cell sequencing, super-resolution microscopy, organoid models, and novel electrophysiological methods, have permitted more precise dissection of the T-junction's molecular composition, ion-channel distribution, and electrophysiological properties. Here, we review current knowledge of the T-junction's developmental regulation and multilayered molecular networks, and we detail its functional alterations in both physiological signaling and pathological pain states, with particular emphasis on ion-channel modulation, signal attenuation, and selective transmission mechanisms. Finally, we discuss contemporary pain-intervention approaches and prospects for precision-targeted therapies, aiming to provide a theoretical foundation for future studies in pain physiology and clinical translation.

Postoperative pain is a common complication caused by surgical trauma. Epidemiological studies indicate that the incidence of moderate to severe acute postoperative pain ranges from 41% to 85%, with approximately 10% to 50% of patients potentially progressing to chronic pain. This progression not only significantly impairs patients' quality of life, but also imposes substantial medical and socioeconomic burdens. The mechanisms underlying chronic postoperative pain are highly complex, involving the activation and sensitization of peripheral nociceptors, central sensitization of spinal dorsal horn neurons, and maladaptive alterations in higher-order cortical neural circuits. Additionally, local and systemic inflammatory responses induced by surgical injury, and psychosocial factors, such as anxiety, depression, and sleep disturbances, have all been shown to play critical roles in the transition from acute to chronic postoperative pain. This article systematically reviews the latest advances in risk factors, animal models, pathophysiological mechanisms, and therapeutic strategies of postoperative pain, with particular emphasis on key processes and potential intervention targets involved in the transition from acute to chronic pain, aiming to offer a more solid theoretical foundation and evidence-based guidance for clinical practice.

To investigate the fiber connections between the claustrum (CLA)/insular cortex (IC) and the locus coeruleus (LC), as well as the role of this neural pathway in neuropathic pain, morphological techniques, patch-clamp recording, and chemogenetics were used in this study, to observe the CLA/IC-LC neural pathway in mice, the effects of neuropathic pain stimuli on the electrophysiological properties of CLA/IC neurons, and the impact of regulating the pathway on pain behaviors, respectively. The results showed that: (1) After injecting anterograde tracing virus into the CLA/IC, anterogradely labeled fibers and terminals were observed in the ipsilateral LC. When retrograde tracers were injected into the LC, retrogradely labeled neurons were observed in both the ipsilateral CLA/IC, whereas fewer labeled neurons were observed in the contralateral side; (2) In the neuropathic pain state, the presynaptic release of neurotransmitters from CLA/IC-LC projection neurons was increased, postsynaptic receptor responses were enhanced, and the number of action potential discharges was elevated; (3) Specific inhibition of the CLA/IC-LC neural pathway induced pain responses in sham-operated mice; specific activation of this pathway alleviated pain-related behaviors in neuropathic pain mice. The present results indicate the existence of functional projection from the CLA/IC to the LC. Under neuropathic pain condition, the CLA/IC-LC pathway exhibits enhanced neuronal activity, and selective activation of this pathway produces significant analgesic effects against neuropathic pain.

The purpose of the study was to investigate the role of the long non-coding RNA (lncRNA)_RT1-CE10 and its molecular mechanisms in chronic visceral pain of rats with irritable bowel syndrome (IBS). Sprague-Dawley (SD) rats were exposed to colorectal distention (CRD) stimulation at a pressure of 60 mmHg for 1 min from 8 to 14 days after birth. The visceral hypersensitivity was assessed by measuring electromyographic (EMG) responses of external oblique muscle to CRD at 40 mmHg and 60 mmHg when the rats were 6 weeks old. The expression of lncRNA_RT1-CE10, Iba-1 and MHCII in the spinal cord was detected by RT-qPCR or Western blot. After intrathecal injection of minocycline (an inhibitor of microglia), the expression of Iba-1, MHCII and the visceral hypersensitivity were determined by Western blot and EMG, respectively. After intrathecal injection of AAV-lncRT1-CE10 and AAV-shlncRT1-CE10, the expression of Iba-1 and MHCII was examined by Western blot, respectively. The results showed that the expression of lncRNA_RT1-CE10 was decreased in the spinal cord of IBS rats, while the expression of Iba-1 and MHCII was increased. Inhibition of microglial activation by minocycline attenuated visceral hypersensitivity in IBS rats. Over-expression of lncRNA_RT1-CE10 decreased the Iba-1 and MHCⅡ levels in IBS rats, while knockdown of lncRNA_RT1-CE10 increased the Iba-1 and MHCⅡ levels in control rats. Collectively, these results demonstrate that lncRNA_RT1-CE10 attenuates visceral hypersensitivity by inhibiting microglial activation in IBS rats.

This study aimed to investigate the role of 5-hydroxytryptamine 1A (5-HT_1A) receptors in the anterior cingulate cortex (ACC) in regulating the affective pain in rats. In the ACC, normal saline (NS), the 5-HT_1A receptor agonist 8-OH-DPAT or the 5-HT_1A receptor antagonist WAY-100635 was pre-injected respectively. A persistent inflammatory pain model was established by subcutaneously injecting 0.08 mL of complete Freund's adjuvant (CFA) into the left hind paw of rats, which was then paired with a specific environment to induce a conditioned place avoidance (CPA) response. Then the electroacupuncture (EA, 10 Hz, 3 mA) was applied to stimulate the Huantiao acupoint (GB30). The CPA responses of rats in the pain-paired environment and the firing activities of ACC neurons were simultaneously observed. Subsequently, open-field behavior, paw withdrawal latency (PWL), and 50% paw withdrawal threshold (PWT) tests were conducted. The results showed that: (1) Rats injected with CFA showed significant reductions in PWL and 50% PWT, and spent less time in the "pain-paired environment" and the center of the open field, compared to the control group (P < 0.05). (2) Immunofluorescence double-labeling results showed a high co-expression of Fos protein and 5-HT_1A receptors in the ACC of the EA-treated normal rats. (3) Pre-treatment with the 5-HT_1A receptor agonist 8-OH-DPAT (8 μg) in the ACC alleviated CFA-induced affective pain (P < 0.05) and reversed the increase in firing frequency of pyramidal neurons in the ACC induced by CFA (P < 0.05). (4) Pre-treatment with the 5-HT_1A receptor antagonist WAY-100635 (8 μg) in the ACC, combined with EA stimulation, reversed the CPA-like behavioral responses induced by CFA in rats and increased the firing frequency of pyramidal neurons in the ACC (P < 0.05). These results suggest that the 5-HT_1A receptors in ACC mediate the alleviating effect of EA on the affective pain of CFA-induced rats.

Visceral pain (VP) refers to pathological pain originating from the thoracic, abdominal, or pelvic regions. Characterized by poor localization and prolonged duration, VP significantly impacts the physical and mental health of patients. Unlike somatic pain, the neural pathways involved in visceral sensation are complex and the pathogenic factors are diverse, leading to incomplete understanding of the production and neural regulation mechanism of VP. Recent studies have identified widespread expression of P2X receptors across multiple systems, including the nervous, cardiovascular, and immune systems, and have demonstrated their important role in pain perception and modulation. Evidence suggests that aberrant purinergic signaling plays a critical role in the development and progression of VP, indicating that purinergic signal transduction has emerged as a potential novel therapeutic target for VP-related disorders. This review summarizes current advances in the regulatory mechanisms mediated by the P2X receptor family in VP, aiming to provide new insights for clinical management of VP.

Pruritus, a complex multidimensional sensation accompanying diverse dermatological and systemic disorders, affects a substantial global population. Nevertheless, the pathophysiological mechanisms underlying chronic pruritus remain incompletely understood. Standardized experimental paradigms for inducing pruritus are essential for establishing a foundational understanding of chronic pruritus. This study aimed to develop a standardized laboratory protocol for pruritus induction, investigate the relationships between sensitivities to different pruritus modalities, and explore the associations of pruritus sensitivities with pain sensitivity and other somatosensory sensitivities, thereby exploring the potential neural mechanisms. This work recruited 124 healthy participants and employed three validated pruritus induction paradigms: mechanical stimulation via calibrated feather brushing, chemical stimulation via epicutaneous application of 1% histamine dihydrochloride solution, and electrically evoked pruritus using high-frequency, low-intensity transcutaneous electrical nerve stimulation. Concurrent Quantitative Somatosensory Testing assessed subjective itch intensity and its correlation with other somatosensory profiles. All three paradigms effectively evoked significant pruritic sensations. Critically, no statistically significant differences were observed in subjective intensity ratings across the induction methods. Correlational analysis revealed significant positive associations between intensities evoked by feather brushing and histamine application, and between feather brushing and electrical stimulation. However, no significant correlation was found between histamine-evoked and electrically evoked itch intensities. This dissociation suggests both shared and distinct neural substrates mediate processing of different pruritus modalities. Furthermore, the study identified complex interactions between pruritus and other somatosensory modalities. Feather-evoked mechanical itch intensity demonstrated a significant negative correlation with mechanical pain thresholds. Similarly, histamine-evoked chemical itch intensity showed a significant negative correlation with heat pain threshold as well as heat pain tolerance thresholds. This work establishes a rigorous methodological foundation for future mechanistic research into pruritus and facilitates the development of targeted therapeutic strategies. The established paradigm in this study can serve as a core tool for objectively assessing an individual's itch sensitivity, deepen the understanding of itch perception, and act as an objective indicator for evaluating the progression of chronic itch disorders and the efficacy of their treatment in clinical practice.

Lipocalin 2 (LCN2), a member of the lipocalin superfamily, is expressed and secreted by various cells and functions as a transport protein for lipophilic small molecules such as steroids, lipopolysaccharides, iron and fatty acids. LCN2 plays a significant role in pain modulation, particularly in the development and maintenance of inflammatory pain and chronic neuropathic pain. Its mechanisms involve the regulation of neuroinflammation and the modulation of neuron-glia interactions. LCN2 also demonstrates notable effects in itch regulation, where it binds to specific receptors and activates downstream signaling pathways, contributing to the induction and persistence of chronic itch. This review summarizes recent advances in the fundamental research on LCN2 in the regulation of chronic pain and itch, and discusses its potential value as a therapeutic target, aiming to provide a theoretical foundation for developing novel treatment strategies.

The gracile nucleus (GR), conventionally regarded as a primary relay in the ascending somatosensory pathway, plays a pivotal role in processing fine-touch, vibration, and proprioceptive information originating from the lower body. The fidelity of this processing is fundamental to sensory perception and motor coordination. We employed single-nucleus RNA sequencing (snRNA-seq) to establish a high-resolution, comprehensive transcriptomic atlas of the adult mouse GR. We systematically dissected the cellular architecture of the GR. Our analysis delineated all major neuronal and non-neuronal populations, and revealed a rich diversity of excitatory projection neuron subtypes, each characterized by a unique transcriptomic signature and a distinct spatial organization. Functional gene enrichment analysis unveiled a striking dichotomy in the roles of these subtypes. We identified a cohort of "conduction-type" neurons, specialized for the rapid and high-fidelity transmission of core somatosensory information, thereby preserving the integrity of the somatosensory map. In contrast, a second cohort of "modulatory-type" neurons demonstrated enriched expression of a diverse repertoire of neuropeptides, including somatostatin and cholecystokinin. These neurons are positioned to exert state-dependent modulation over the principal sensory pathways, fine-tuning information throughput in response to behavioral context or internal states such as arousal and attention. Notably, our findings reveal that these excitatory neurons do not exist as discrete, static populations. Instead, they are organized along a continuous transcriptional spectrum, which appears to represent a trajectory of sensory learning and adaptation. One pole of this continuum, representing an "adapted" state, exhibited significant enrichment of activity-dependent immediate-early genes integral to synaptic plasticity, learning, and memory, such as Fos, Arc, and Npas4. By elucidating this intricate cellular architecture and intrinsic plasticity, our study provides novel insights into information processing within the somatosensory system and offers a valuable resource for investigating the pathophysiology of related disorders, including chronic pain and sensory neuropathies.

Dopamine, as a catecholamine neurotransmitter widely distributed in the central nervous system, is involved in physiological functions such as motivation, arousal, reinforcement, and movement through various dopamine signaling pathways. The hippocampus receives dopaminergic neuron projections from regions such as the ventral tegmental area, locus coeruleus, and substantia nigra. Through D1-like and D2-like receptors, dopamine exerts significant regulatory effects such as spatial navigation, episodic memory, fear, anxiety, and reward. This review mainly summarizes the research progress on the functions of dopamine in the hippocampus from aspects including the sources of dopamine, receptor distribution and function, and the association of hippocampal dopamine system dysregulation with neurodegenerative diseases. The aim is to provide insights into the involvement of the dopamine system in hippocampal functions and the diagnosis and treatment of related diseases.