In a menopausal animal model (ovariectomized rats) and young women, we investigated the effect of estrogen (E₂) on thermoregulation via peripheral cold receptors (TRPA1, TRPM8, and TREK). In the menopausal animal model, when cinnamaldehyde or menthol (TRPA1 or TRPM8 agonist) was applied, E₂ affected thermoregulation via TRPM8, not TRPA1. In young women, when menthol was applied, cold-induced discomfort increased only in the preovulatory phase when the E₂ concentration is higher. In the menopausal animal model, when ostruthin, a TREK agonist, was administered, E₂ enhanced the increase of body temperature induced by ostruthin through suppression of heat dissipation. E₂ increased Trek1 mRNA in the dorsal root ganglia. The TREK agonist increased the amplitude of the slow ventral root potential of sensory nerves in in vitro spinal cord preparations. The increase of TREK expression and amplitude may augment cold reception. E₂ may contribute to female thermoregulation in the cold via TRPM8 and TREK1.

The autonomic nervous system plays a critical role in maintaining homeostasis by regulating respiration, circulation, thermoregulation, and metabolic processes. It consists of efferent pathways projecting from the central nervous system to peripheral organs and afferent pathways transmitting sensory information back to the central nervous system. In animal models, organ-specific autonomic nerve activity has traditionally been assessed using electrophysiological recordings from nerves innervating the target organ. Recent advances have enabled chronic recordings of sympathetic nerve activity in awake rodents using wired and wireless electrode systems, providing valuable insights into physiological regulation under conscious conditions. In our recent work, we successfully recorded renal sympathetic nerve activity, arterial pressure, and heart rate in mice following electrode implantation under anesthesia, and confirmed the presence of baroreceptor reflexes after recovery to the awake state. This review summarizes current methodologies for recording autonomic nerve activity in awake animals, discusses technical challenges such as motion-induced artifacts, and highlights future directions for developing stable, long-term recording techniques in mice to facilitate studies of autonomic regulation over weeks to months.

Volitional motor signals. i.e., central command, simultaneously activate central somatomotor and autonomic pathways, thereby regulating both muscular activity and cardiovascular responses during voluntary exercise. Early literature from the late nineteenth century suggested the essential role of the brain in autonomic cardiovascular adjustments to exercise. However, the underlying mechanisms remain largely unexplored. This article reviews the research history addressing this topic, highlighting the utilization of advanced technologies of each era, such as functional neuroimaging and optogenetics. Specifically, our recent investigations into subcortical neural circuits that transmit central command signals, thereby driving not only locomotor activity but also autonomic cardiovascular responses are discussed. Potential directions for future research in this field are also examined.

In 2017, the International Association for the Study of Pain defined nociplastic pain as pain arising from central nervous system plasticity without clear evidence of tissue injury or neuropathy. This “third category” challenges the conventional view that pain always results from identifiable pathology and can be eliminated by treating its cause. In parallel, the WHO introduced “primary chronic pain” in ICD-11, referring to pain persisting over three months without structural or neuropathic origins. To study underlying mechanisms, animal models have been developed in which transient inflammation triggers long-lasting, bilateral hypersensitivity without injury, allowing evaluation of centrally acting analgesics. Evidence from imaging and experimental studies shows that chronic pain involves widespread brain regions, particularly those linked to emotion, such as the parabrachial nucleus and central amygdala. A paradigm shift views pain as a survival-related signal generated by the brain, whose chronicity reflects maladaptive plasticity requiring therapeutic re-conceptualization.

Neuromodulation includes surgical approaches such as deep brain stimulation (DBS), spinal cord stimulation (SCS), and motor cortex stimulation (MCS), as well as non-invasive methods including repetitive transcranial magnetic stimulation (rTMS), transcranial electrical stimulation, and transcranial focused ultrasound stimulation (TUS/tFUS). For the treatment of intractable pain, SCS typically targets the dorsal columns and dorsal horn, while DBS commonly targets the ventroposterior nucleus of the thalamus and the periaqueductal gray matter. rTMS applied to the primary motor cortex has been introduced as a non-invasive alternative to MCS, and numerous randomized controlled trials have been conducted. More recently, DBS, rTMS, and TUS/tFUS targeting the ventral striatum and anterior limb of the internal capsule, medial thalamic nuclei, insular cortex, and anterior cingulate cortex have also been explored. Advances in the understanding of the functional localization and neural circuits of the central nervous system involved in pain perception, together with technological innovations in neuromodulation, are expected to lead to the development of novel therapeutic approaches.

Parkinson’s disease (PD) has traditionally been regarded as a central nervous system disorder characterized predominantly by motor symptoms. However, recent advances have led to the recognition of PD as a multisystem disease involving widespread non-motor symptoms, notably autonomic dysfunction. According to Braak’s hypothesis, abnormal α-synuclein aggregates initially appear in the dorsal motor nucleus of the vagus nerve and the olfactory bulb, subsequently spreading in an ascending manner throughout the central nervous system. This suggests that peripheral autonomic nervous system involvement may precede the onset of motor symptoms. This review outlines the significance of autonomic dysfunction in PD, focusing particularly on the clinical utility of ¹²³I–MIBG myocardial scintigraphy. As the only currently available non-invasive marker capable of quantitatively evaluating non-motor symptoms, MIBG myocardial scintigraphy plays a crucial role in early diagnosis and differential diagnosis of PD. Furthermore, it holds promise as a tool for detecting prodromal PD．

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic failure, parkinsonism, and cerebellar ataxia. Gerhardt syndrome denotes inspiratory dyspnea with laryngeal stridor caused by vocal fold dysfunction. It occurs frequently in patients with MSA and has been associated with nocturnal, potentially fatal upper-airway obstruction and sudden death. Two principal mechanisms have been proposed: (1) dystonic overactivity of the adductor muscles of the vocal folds; and (2) neurogenic atrophy or denervation of the posterior cricoarytenoid, the sole abductor of the vocal folds. Recent studies indicate that these abnormalities are not mutually exclusive and may coexist within the same patient. This mini-review summarizes current histopathological findings encompassing laryngeal muscle pathology and brainstem changes relevant to Gerhardt syndrome in MSA and outlines their clinical implications. By integrating recent evidence, we highlight how a coexistence model of adductor dystonia and abductor denervation refines our understanding of pathophysiology and may guide individualized management strategies in clinical practice.