Non-motor symptoms including autonomic dysfunction are prevalent in Parkinson’s disease (PD). Autonomic dysfunctions significantly influence ADL (Activities of Daily Living) and QOL (Quality of Life). Lower urinary tract symptoms (LUTS) such as overactive bladder symptoms (OAB) characterized by the presence of urinary urgency and urinary frequency are prevalent in PD patients. It is also well known that many PD patients are suffering from constipation which usually precedes the onset of motor symptoms. However, the relationships between QOL and LUTS and constipation are not well understood. In this symposium, we will review the clinical characteristics of LUTS and constipation and their correlation to QOL in patients with PD.

Spinal cord injury causes a wide range of impairments in autonomic functions due to disruption of sympathetic and parasympathetic circuitry. Autonomic impairments such as in micturition, thermoregulation, cardiovascular, gastrointestinal, sexual, and immune function severely affect the quality of life of patients. However, the underlying neural mechanisms that impair or recover the autonomic functions have not been well studied in spinal cord injury, compared to those of the motor and sensory systems. In this paper, I review the current status of basic research on the autonomic system in spinal cord injury and discuss about future prospects in this field. Understanding the processes disrupting the circuits as well as repairing such as by neural stimulation and regeneration will contribute to develop novel therapeutic approaches to restore autonomic functions.

The autonomic nervous system is involved in regulating the immune system, however, it is often impaired by an autoimmune mechanism in autoimmune neurological diseases. Autonomic symptoms and signs are presented in diseases that selectively impair the autonomic nervous system, as seen in autoimmune autonomic ganglionopathy, or cause autonomic lesions as a subset of neurological lesions, as seen in multiple sclerosis and autoimmune encephalitis. The lesion sites include: the central autonomic nervous system (the brain and spinal cord) which is impaired in multiple sclerosis; peripheral autonomic nerves which are impaired in autoimmune autonomic ganglionopathy; peripheral autonomic nerve endings which are impaired in Lambert-Eaton syndrome; and effectors which are impaired in idiopathic acquired generalized anhidrosis, a sweat gland disorder. From the aspect of diagnosis, characteristic autonomic symptoms, such as area postrema syndrome, seen in neuromyelitis optica, may indicate certain neurological diseases. The autonomic symptoms and signs in autoimmune neurological diseases and their pathogenesis are explained.

Pain and itch are recognized as antagonistic sensations; pain suppresses itch and inhibition of pain generates itch. There is still a lack of evidence about the neural processing of the pain-itch interaction in the central nervous system. To reveal the such mechanism, we focused on the orexin (ORX) neurons in the lateral hypothalamus, which mediate various “defense responses” when animals confront stressors. We found that the pruritogen-induced scratching behaviors were significantly inhibited in ORX-neuron-ablated (ORX-abl) mice. The exaggerated pain behavior and attenuated itch behavior observed in ORX-abl mice indicated that ORX neurons modulate pain and itch in an opposite way, i.e., pain relief and itch exacerbation. In addition, most of the ORX neurons responded to both pain and itch input. Our results suggest that ORX neurons inversely regulate pain- and itch-related behaviors, which could be understood as a defense response to cope with stress environment.

We reported that estradiol (E2) affects the medial preoptic area in the hypothalamus, a thermoregulatory center, decreases the T_skn (skin temperature) of the tail, and maintains the T_b (body temperature) in the cold in ovariectomized rats. E2 facilitates the thermoregulatory behavior, evaluated by the tail-hiding behavior of rats hiding their tails under their bodies, and suppressed neural activity in the insula of the brain. These results indicate that E2 centrally affects and facilitates autonomic and behavioral thermoregulation in the cold. The effect of E2 on thermoregulatory responses through cold receptors, transient receptor potential melastatin-8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1), were investigated. E2 suppressed the elevation of T_b by the application of menthol, a TRPM8 agonist; however, it did not affect T_b or T_skn of the tail after the application of cinnamaldehyde, a TRPA1 agonist. Thus, E2 modifies thermoregulation via TRPM8. In young women, T_skn decreased in all phases of the menstrual cycle after menthol application to the dorsum of the foot; however, cold unpleasantness occurred only in the preovulatory phase, the higher E2 concentration phase. Thus, E2 induces mental hypersensitivity to the cold through TRPM8. In ovariectomized rats, the effect of E2 on thermoregulation was investigated through the TWIK-related K⁺ channel (TREK), a new cold receptor. E2 administration increased T_b after the administration of ostruthin, a TREK agonist. These results indicate that E2 modulates thermoregulation in the cold through TRPM8, TREK, and centrally.

Laryngeal stridor and obstructive sleep apnea due to paradoxical adduction of the vocal cords during inspiration in multiple system atrophy are well known, but laryngospasm has received less attention. We report the case of a 71-year-old man with multiple system atrophy who suffered sudden respiratory failure due to laryngospasm. At the age of 68, he developed a gait disturbance and visited our department. He presented cerebellar ataxia and orthostatic hypotension, and brain MRI showed cerebellar and pontine atrophy. He was diagnosed with multiple system atrophy. His condition progressed slowly. At the age of 71, he suddenly suffered breathing difficulty without any triggers during the daytime, became unconscious, and was taken by ambulance to our hospital. He presented laryngeal stridor and hoarseness. Chest CT revealed infiltrates in the left lower lung field. He was diagnosed as having aspiration pneumonia and treated with antibiotics. Laryngoscopy showed fixed vocal cords at the paramedian, and the sudden respiratory insufficiency and laryngeal stridor were considered to have been caused by laryngospasm. One week after admission, the laryngeal stridor disappeared. We subsequently confirmed that the hoarseness had disappeared. Paradoxical contraction of the vocal cord adduction muscle is seen both in laryngeal spasm and stridor in multiple system atrophy, and these conditions may involve an exaggerated laryngeal adductor reflex associated with neurodegeneration in multiple system atrophy.