Presbyopia is the decrease of accommodative power as a part of the structural and functional physiological aging process. Aging has been regarded as an interesting evolutionary negligence resulting in irreversible visual impairment and psychological shock. Despite reviewing the many theories proposed over time, the dispute is still unresolved; however, the mechanism of the lens itself appears to be the most important factor in the determination of presbyopia. The Helmholtz theory of the regulation mechanism is the most widely accepted. Weakening of the accommodative power occurs due to hardening of the lens capsule and leads to a convergence–accommodation (near triad) cross-link. The attenuation of the adjustment increases the exophoria at near. From this, it is conceivable that the fusion convergence becomes stronger. The miosis accompanying the near vision also eliminates blurring by increasing the depth of focus so as to compensate for the decrease in accommodative power. Hence, the adaptation of near triad accompanying presbyopia was discussed.
Human papilloma virus vaccination associated neuro-immunopathic syndrome (HANS) is a circumventricular organs dysregulation syndrome, derived from neuro-endocrinological disorders of the hypothalamus and its limbic networks. The average score on the modified Rankin Scale reaches a maximum at 4 years after vaccination. We studied blood, CSF, brain MRI, SPECT, muscle CT, EEG and endocrine tests. We found high blood pyruvates and uric acid, low blood 25 vitamin D hydroxide and LDH, and elevated CSF NSE, which indicates immunosuppression and homeostatic dysregulation of energy metabolism (glycolysis system). Severe HANS patients were diagnosed as sarcopenia by muscle CT (measurement of lower thigh circumference), grip power and BMI, and as osteoporosis by bone mineral quantitative examination. Muscle echograms showed a brightness increase. Brain MRI of a severe HANS patient revealed progress of dilated third ventricle and atrophic cerebral cortex. Hypothalamic disorders were confirmed by abnormal insulin tolerance test results, marked hypoglycemic responses after OGTT, low cortisol levels, and absence of circadian changes in ACTH and cortisol. RI cisternography showed mild degrees of spinal fluid leakage, while a spinal fluid production marker (brain-type transferrin) remained normal. Abnormal results of CVRR and orthostatic examinations indicated both parasympathetic and sympathetic disorders. Decreased reactive hyperemia index scores indicated impaired vascular endothelial function. Pulse wave velocity test results showed increased vascular resistance values for age. The ankle brachial index results were normal. Alpha rhythm abnormalities in EEG indicated thalamic disorders. Decreases in flow at the thalamus and anterior cingulate gyrus in SPECT indicated disorders of the diencephalon and limbic system. We discuss pathogenic mechanism of HANS and its various issues.
Iron is an essential nutrient for myelination, neurotransmission and electron transfer in the respiratory chain. Transferrin (Tf), an iron transporter, is mainly biosynthesized in the liver, but Tf is also biosynthesized in the brain; i.e., oligodendrocytes some neurons, and choroid plexus, a cerebrospinal fluid (CSF) producing tissue. CSF contains two glycan isoforms of Tf: brain-type Tf and serum-type Tf. Brain-type Tf is uniquely glycolsylated with biantennary asialo- and agalacto-complex type N-glycans that carry bisecting β1,4-GlcNAc and core α1,6-Fuc. The glycans of serum-type Tf are similar to those of serum transferrin. We speculate that brain-type Tf could be a biomarker of altered CSF production based on the following observations: (i) choroid plexus epithelial cells highly express Tf which carries N-acetylglucosamine-terminated glycans, (ii) brain-type Tf decreases in idiopathic normal pressure hydrocephalus (iNPH), in which CSF production is suspected to decrease, and (iii) brain-type Tf increases in spontaneous intracranial hypotension (SIH), in which CSF production is suspected to increase. Thus brain-type Tf could be a useful biomarker for CSF-related abnormalities.
To understand the myofascial pain mechanism, we analyzed the mechanism of delayed onset muscle soreness (DOMS), which is induced by lengthening contraction and used for the study of myofascial pain syndrome. Micro injuries and following inflammation were not essential for generation of DOMS. Two pathways leading to muscular mechanical hyperalgesia were identified: One is bradykinin-like substance released during lengthening contraction-B2 bradykinin receptor-nerve growth factor pathway, the other is COX-2-prostaglandin-glial cell-line derived neurotrophic factor pathway. Both trophic factors were produced by muscle cells/satellite cells and sensitize thin-fiber muscle afferents to mechanical stimulation, resulting in muscular mechanical hyperalgesia. These results show that there are factors in the work performed by muscle in daily life that stimulate production of sensitizing neurotrophic factors, resulting in muscle mechanical hyperalgesia.
Pain is “an unpleasant sensory and emotional experience” (the International Association for the Study of Pain). As this definition predicts, brain structures involved in emotion, such as the amygdala, cingulate cortex, insular cortex, and nucleus accumbens, are strongly activated in patients and animals with various types of pain. In addition to the sustained activation during spontaneous pain in patients with persistent pain, the amygdala shows elevated activity in various types of subacute to chronic pain models. Recently accumulated lines of evidence also indicate that the amygdala not only gets activated by receiving nociceptive information but also regulate the peripheral/spinal cord nociception level through descending modulatory pathways. Similar “loop” regulation is also reported with other emotion-associated structures as listed above. Here we propose that the primordial biological significance of the emotion would lie in a “hub” function to optimize and control the sensory gain, behaviors and internal environments with reference to the monitored status of the whole body.
Noxious mechanical stimulation of the skin increases serotonin (5-HT) release in the central nucleus of the amygdala (CeA) in anesthetized rats. We introduce our recent results on the contribution of corticotropin releasing factor (CRF) receptors in the dorsal raphe nucleus (DRN) to 5-HT release in the CeA in response to noxious cutaneous stimulation. Release of 5-HT in the CeA was monitored by microdialysis before and after 10-min stimulation by pinching. Increased 5-HT release in the CeA in response to pinching was abolished by either non-selective CRF receptor antagonism or selective CRF2 receptor antagonism in the DRN, but not by selective CRF1 receptor antagonism. These results suggest that 5-HT release in the CeA in response to noxious mechanical stimulation of the skin is mediated via the CRF2 receptors in the DRN.
The thyroid gland is dually innervated by sympathetic and parasympathetic (superior laryngeal nerve: SLN) nerves. However, their contribution to the regulation of the secretory function of the thyroid remains unclear. Recently, our experiments, performing of electrical stimulation of cervical sympathetic trunks and SLNs and collecting the thyroid venous blood of anesthetized rats, showed that hormonal secretion from the thyroid gland is rapidly and antagonistically regulated by sympathetic and parasympathetic efferent nerve activity, suggesting that excitation of the myelinated afferent fibers of SLN may induce reflex increases in hormonal secretion from the thyroid gland. We also found that a natural stimulation triggering this kind of reflex is mechanical stimulation of the pharynx.
Acupuncture has been performed to treat erectile dysfunction (ED) in patients undergoing several factors. Among our patients with psychogenic, endocrine, vascular, diabetic or neurogenic ED, 58% (15 out of 26 cases) indicated improved ED with manual acupuncture at sacral region (Zhongliao, BL-33). Moreover, we reported one case of ED in a sildenafil (phosphodiesterase type 5; PDE-5) non-responder was successfully treated with acupuncture at BL-33. The specific underlying mechanism of acupuncture on erectile function remain unknown. We have indicated some findings using intracavernousal pressure (ICP) in anesthetized rats. Electro acupuncture (EA) stimulation at 5.0 mA of the sacral region decreases ICP of erectile state via sympathetic nerve. On the other hand, ICP is increased by EA to the sacral region in non-erectile state. An increase in ICP induced by EA is mediated by nitric oxide releases via excitation of the pelvic nerve descending from the central nervous system. Although the evidence is insufficient to suggest that acupuncture is an effective intervention for treating ED, select populations of ED patients may benefit.
Acupuncture is thought to be effective for peripheral circulatory disturbances, such as in arteriosclerosis obliterans, Raynaud’s phenomenon, shoulder stiffness, and sensitivity to cold, as acupuncture treatment improves local blood flow, which can flush out algesic or sensitizing substances. With regard to the mechanisms underlying the improvement in local blood flow caused by acupuncture, calcitonin gene-related peptide released from sensory nerve terminals may be partially responsible. Recently, it was also suggested that nitric oxide and adenosine are involved in the increase in local blood flow induced by acupuncture. We examined whether muscle sympathetic nerve activity (MSNA) plays a role in the increases in blood flow following acupuncture. Acupuncture did not alter MSNA in this study, indicating that the increases in blood flow are not mediated by the suppression of MSNA.
Orexin is reported to be involved in the regulation of stress responses. The aim of this study was to investigate the effects of press tack needle (PTN) treatment on social isolation stress and the participation of the control of orexin in this effect. Rats were divided into a non-stress group (Control), stress group (Stress) and stress plus PTN treatment group (PTN). The rats in the PTN and Stress groups were housed alone for eight days. In the PTN group, a PTN was fixed on the GV 20 acupuncture point (Baihui) on day 7. We measured the stress behavior based on the time the rats showed aggressive behavior and measured the levels of plasma corticosterone and orexin A on day 8. The duration of aggressive behavior was significantly increased in the Stress group versus the Control group, although the increase was inhibited in the PTN group. The levels of plasma corticosterone and orexin A were significantly increased in the Stress group versus the Control group, although these increases were inhibited in the PTN group. PTN may inhibit the response to social isolation stress, and the control of orexin is thought to be one mechanism underlying this phenomenon.
During the 19th century, the autonomic control of salivary glands attracted great attention of the famous physiologists. The parasympathetic fibers to induce salivary secretion was discovered by Ludwig (1850), who observed copious salivary flow from the submaxillary gland of the dog by stimulation of the lingual nerve. Bernard (1858) traced these fibers in the chorda tympani, and considered that the secretory fibers were identical to the vasodilator fibers. Oppositely, Heidenhain (1872) proved that the seretory fibers and the vasodilator fibers were pharmacologically different. Complementary secretory fibers of the sympathetic origin were found by Heidenhain (1878) and Langley (1878); the parasympathetic and sympathetic fibers synergistic effects on salivary glands. The sympathetic fibers to evoke constriction of myo-epithelial cells of salivary ducts were demonstrated by Eckhard (1969), a pipil of Ludwig. Meanwhile, paradoxical salivary secretion from the submaxillary gland after the section of the chorda tympani, or paralytic secretion, was described by Bernard (1862), Heidenhain (1868), and Langley (1885). Emmelin et al. (1950) clarified that paralytic secretion was caused by denervation supersensitivity, and that the parasympathetic denervation of salivary glands, as well as the sympathetic denervation, produced non-specific supersensitivity to both adrenaline and pilocarpine. Considering the complex nature of the autonomic control of salivary glands, the physiology of sweat glands, which are another secretory organ, seems to be oversimplified. Furthermore, the mechanism of denervation supersensitivity should be reconsidered.
The cause of spontaneous cerebrospinal fluid (CSF) hypovolemia is currently considered as CSF leak due to latent spinal injury. Schaltenbrand, the first describer of spontaneous CSF hypovolemia, asserted that the essential cause of CSF hypovolemia was reduced CSF production whether there was CSF leak or not, however. We herein provide a historical review on CSF hypovolemia. Before Schaltenbrand, Hosemann (1909) and Haug (1932) stated that CSF hypovolemia following lumbar puncture was caused by a lack of compensatory CSF production due to underlying autonomic instability, which was corresponding to the current postural tachycardia syndrome (PoTS). Schaltenbrand (1938, 1940) reported 7 cases of spontaneous CSF hypovolemia. Emphasizing the presence of xanthochromia in these cases, he concluded that the cause of spontaneous CSF hypovolemia was reduced CSF production from the choroid plexus, because he had confirmed that so-called CSF was a mixture of liquids produced from the perivascular spaces and from the choroid plexus, and that the former contained larger amount of protein than the latter. Meanwhile, Geller (1940) reported that overwhelming majority cases of CSF hypovolemia accompanied autonomic instability, Recently, Graf et al. (2018) suggested the comorbidity of CSF hypovolemia and PoTS in the same individuals. Sympathetic activity is increased in PoTS patients, while CSF production from the choroid plexus is reported to be under the inhibitory control of the sympathetic nervous system (Lindvall et al., 1978; Haywood et al., 1979). Considering these historical articles together, the essential cause of spontaneous CSF hypovolemia seems to be underlying PoTS.
Up to 18% of multiple system atrophy (MSA) patients may start with bladder dysfunction alone without any other symptoms. In particular some men with MSA had undergone prostatic surgery before the correct diagnosis was made. In these patients, pathology may start at the sacral spinal cord first. MSA patients need regular check of their post-void residuals by an ultrasound echography. And when necessary, clean, intermittent catheterization (CIC) by the patients or their caregivers should start. Bladder dysfunction in MSA patients need special care for maximizing patients’ quality of life.
We investigated the effects of tactile (stroking) and thermal stimulation of the back on heart rate and its autonomic mechanism in healthy young women in a prone position. Three stimuli were added at random: 1) stroking over a towel, 2) stroking over a heated towel (thermal + stroking), and 3) putting a towel on the back without stroking. During stroking stimulation, the heart rate and sympathetic activity indices of low-frequency (LF)/high-frequency (HF) and LFnu decreased, and the parasympathetic activity index HFnu increased. Thermal + stroking stimulation prolonged these effects. Although the same effect was also observed after putting a towel on the back without stroking, the duration of the effects was shorter than that of the stroking stimulation. No effect was observed in the control experiment. The score on the relaxation index significantly increased after stroking stimulation, and the score was even higher when thermal + stroking stimulation was delivered. The above findings suggest that heart rate decreases through changes in both the sympathetic and parasympathetic nerve activities due to mechanical and thermal stimulations to the back. It appears that the psychological relaxation was also partially involved in the decrease of heart rate.