Sympathetic modulation of hindlimb muscle contractility is altered in aged rats.

It has recently been demonstrated that reflex excitation of muscle sympathetic nerves triggered by muscle contraction contributes to the maintenance of tetanic force (TF) in rat hindlimb muscles. We hypothesized that this feedback mechanism between the contraction of hindlimb muscles and the lumbar sympathetic nerves declines during aging. In this study, we examined the contribution of sympathetic nerves on skeletal muscle contractility in young adult (4-9 months old, n = 11) and aged (32-36 months old, n = 11) male and female rats. The tibial nerve was electrically stimulated to measure the TF of the triceps surae muscles resulting from motor nerve activation before and after cutting or stimulating (at 5-20 Hz) the lumbar sympathetic trunk (LST). The TF amplitude decreased by cutting the LST in the young and aged groups; however, the magnitude of the decrease in TF following transection of the LST in the aged rats (6.2%) was significantly (P = 0.02) smaller compared with that in the young rats (12.9%). The TF amplitude was increased by LST stimulation at ≥ 5 Hz in the young and ≥ 10 Hz in the aged groups. The overall TF response to LST stimulation was not significantly different between the two groups; however, an increase in muscle tonus resulting from LST stimulation, independent of motor nerve stimulation, was significantly (P = 0.03) greater in aged compared with young rats. The sympathetic contribution to support motor nerve-induced muscle contraction declined, whereas sympathetic-mediated muscle tonus, independent of motor nerve activity, was augmented in aged rats. These changes in sympathetic modulation of hindlimb muscle contractility may underlie the reduction of skeletal muscle strength during voluntary contraction and rigidity of motion during senescence.

Managing office worker presenteeism by providing financial aid for acupuncture therapy: a pragmatic multicenter randomized comparative study.

To evaluate whether financial aid for acupuncture therapy is beneficial for non-manufacturing job workers (office workers) who are aware of reduced job performance due to health issues (presenteeism), a four-wk pragmatic multicenter randomized controlled trial was conducted with office workers who were aware of their presenteeism. The control group only implemented the workplace-recommended presenteeism measures, whereas the intervention group received financial aid for acupuncture therapy of up to 8,000 JPY (Japanese yen) in addition to implementing the presenteeism measures recommended by each workplace. The major outcome measure was the World Health Organization Health and Work Performance Questionnaire relative presenteeism score. A total of 203 patients were assigned to the intervention (n=103) and control (n=108) groups. The intervention group underwent a median of 1.0 (interquartile range [IQR], 1.0 to 2.0) sessions of acupuncture for neck disorders (64%), back disorders (16%), and depressed mood/anxiety/irritation (5%), among others. Results showed that the intervention group had slightly better job performance than the control group (effect size [r]=0.15, p=0.03). Financial aid for acupuncture therapy may help compensate for losses incurred by enterprises in the form of 14,117 JPY per worker a month.

Mild thermal stimulation of the buttock skin increases urinary voiding efficiency in anesthetized rats.

In the present study, we examined the effects of mild thermal stimulation of the skin on voiding efficiency using urethane-anesthetized rats with reduced voiding efficiency. Spontaneous urination was induced by infusing saline. For each voiding, the voiding efficiency was calculated from the voided volume and the bladder capacity measured. A Peltier thermode was attached to the buttock skin to apply stimulation: cooling between to 25 °C and 35 °C, every 20 s throughout the saline infusion. The voiding efficiency was 29 ± 9 % (mean ± SD) before stimulation and increased significantly by 10-15 % during stimulation. During thermal stimulation, the maximum vesical pressure during micturition was unchanged, but the urethral relaxation duration was significantly prolonged. Applying local anesthesia to the stimulated skin area abolished the changes in voiding efficiency in response to thermal stimulation. These results suggest that the excitation of cutaneous thermoreceptive afferents modulates urethral function during urination, thereby improving voiding efficiency.

Trigger Point Acupuncture and Exercise for Chronic Low Back Pain in Older Adult: a Preliminary Randomized Clinical Trial.

Background: Exercise therapy is the first choice non-pharmacotherapeutic approach for musculoskeletal pain; however, it often interferes with the implementation and continuation of exercise due to fear-avoidance behaviors. Trigger point acupuncture (TrPAcp) has been reported to reduce musculoskeletal pain. Objectives: To examine the efficacy of exercise combined with TrPAcp compared to exercise alone for older patients with chronic low back pain (CLBP), the most common subjective symptom reported by old people of both sexes in Japan. Methods: In this single-center randomized controlled trial conducted at Teikyo Heisei University, 15 men and women aged ≥ 65 years with low back pain for at least 3 months who met the eligibility criteria were included. The Ex+TrPAcp group received exercise and trigger point acupuncture, while the Ex group received only exercise for 3 months. The main outcome, pain intensity, was measured using the numerical rating scale (NRS). Improvement was defined as a decrease in NRS of ≥ 2 or less than moderate (NRS < 4). Results: The analysis included 7 of 8 cases in the Ex+TrPAcp group and 7 of 7 cases in the Ex group. NRS improved in 6 of 7 and 1 of 7 patients in the intervention and control groups, respectively, with a significant difference between groups (p = 0.03, ϕ = 0.71). Regarding adverse events due to acupuncture, one patient (14.3%) complained of heaviness after acupuncture. Nothing specific was reported with exercise. Conclusion: Compared with Ex alone, Ex+TrPAcp may be more effective therapy for older people with CLBP who do not have an exercise habit.

Influence of Intragastric Administration of Traditional Japanese Medicine, Ninjin'Yoeito, on Cerebral Blood Flow via Muscarinic Acetylcholine Receptors.

Ninjin'yoeito (NYT) is a traditional medicine that has been used for mitigating physical frailty, such as fatigue and anorexia, as well as for cognitive dysfunction. Maintenance of adequate cerebral blood flow (CBF) is important for preventing cognitive dysfunction. The present study aimed to examine the effect of NYT on CBF. Male C57BL/6 J mice were anesthetized with urethane and were artificially ventilated. We measured CBF in the neocortex with laser-speckle contrast imaging for 10 min before administration and 60 min after administration. We administered NYT solution (0.25, 0.5, 1, and 2 g/kg) or vehicle (distilled water; DW) over 5 min via an intragastric catheter. We surgically transected the vagus nerve to investigate its contribution as a neural pathway and intraperitoneally injected atropine to block muscarinic acetylcholine receptors. Finally, we tested the CBF response to cutaneous brushing stimulation applied to the left hind paw (30 sec). CBF decreased after DW administration, starting from 30 min onward, whereas CBF did not change after NYT. The averaged CBF change following DW administration differed from that following NYT (1 g/kg) but not from those following the other doses of NYT. Arterial pressure was not affected by either solution. CBF after NYT (1 g/kg) was not affected by vagotomy but was lower following additional atropine. In response to brushing stimulation, CBF in the right (contralateral) parietal cortex increased. The magnitude of CBF increase following NYT was greater than that following DW. These results suggest that NYT prevents CBF decrease via cholinergic activation independent of vagal activity and enhances the CBF response to somatosensory stimulation.

Maintenance of contractile force of the hind limb muscles by the somato-lumbar sympathetic reflexes.

This study aimed to clarify whether the reflex excitation of muscle sympathetic nerves induced by contractions of the skeletal muscles modulates their contractility. In anesthetized rats, isometric tetanic contractions of the triceps surae muscles were induced by electrical stimulation of the intact tibial nerve before and after transection of the lumbar sympathetic trunk (LST), spinal cord, or dorsal roots. The amplitude of the tetanic force (TF) was reduced by approximately 10% at 20 min after transection of the LST, spinal cord, or dorsal roots. The recorded postganglionic sympathetic nerve activity from the lumbar gray ramus revealed that both spinal and supraspinal reflexes were induced in response to the contractions. Repetitive electrical stimulation of the cut peripheral end of the LST increased the TF amplitude. Our results indicated that the spinal and supraspinal somato-sympathetic nerve reflexes induced by contractions of the skeletal muscles contribute to the maintenance of their own contractile force.

Cerebral artery dilation during transient ischemia is impaired by amyloid ß deposition around the cerebral artery in Alzheimer's disease model mice.

Transient ischemia is an exacerbation factor of Alzheimer's disease (AD). We aimed to examine the influence of amyloid ß (Aß) deposition around the cerebral (pial) artery in terms of diameter changes in the cerebral artery during transient ischemia in AD model mice (APPNL-G-F) under urethane anesthesia. Cerebral vasculature and Aß deposition were examined using two-photon microscopy. Cerebral ischemia was induced by transient occlusion of the unilateral common carotid artery. The diameter of the pial artery was quantitatively measured. In wild-type mice, the diameter of arteries increased during occlusion and returned to their basal diameter after re-opening. In AD model mice, the artery response during occlusion differed depending on Aß deposition sites. Arterial diameter changes at non-Aß deposition site were similar to those in wild-type mice, whereas they were significantly smaller at Aß deposition site. The results suggest that cerebral artery changes during ischemia are impaired by Aß deposition.

Chronic Electrical Stimulation of the Superior Laryngeal Nerve in the Rat: A Potential Therapeutic Approach for Postmenopausal Osteoporosis.

Electrical stimulation of myelinated afferent fibers of the superior laryngeal nerve (SLN) facilitates calcitonin secretion from the thyroid gland in anesthetized rats. In this study, we aimed to quantify the electrical SLN stimulation-induced systemic calcitonin release in conscious rats and to then clarify effects of chronic SLN stimulation on bone mineral density (BMD) in a rat ovariectomized disease model of osteoporosis. Cuff electrodes were implanted bilaterally on SLNs and after two weeks recovery were stimulated (0.5 ms, 90 microampere) repetitively at 40 Hz for 8 min. Immunoreactive calcitonin release was initially measured and quantified in systemic venous blood plasma samples from conscious healthy rats. For chronic SLN stimulation, stimuli were applied intermittently for 3-4 weeks, starting at five weeks after ovariectomy (OVX). After the end of the stimulation period, BMD of the femur and tibia was measured. SLN stimulation increased plasma immunoreactive calcitonin concentration by 13.3 ± 17.3 pg/mL (mean ± SD). BMD in proximal metaphysis of tibia (p = 0.0324) and in distal metaphysis of femur (p = 0.0510) in chronically SLN-stimulated rats was 4-5% higher than that in sham rats. Our findings demonstrate chronic electrical stimulation of the SLNs produced enhanced calcitonin release from the thyroid gland and partially improved bone loss in OVX rats.

Thyroxin and calcitonin secretion into thyroid venous blood is regulated by pharyngeal mechanical stimulation in anesthetized rats.

The effects of the pharyngeal non-noxious mechanical stimulation on the secretion of immunoreactive thyroxin (iT4), immunoreactive calcitonin (iCT), and immunoreactive parathyroid hormone (iPTH) into thyroid venous blood were examined in anesthetized rats. Secretion rates of iT4, iCT, and iPTH were calculated from their concentration in thyroid venous plasma and the plasma flow rate. A mechanical stimulation was delivered to the pharynx by a rubber balloon placed on the tongue that was intermittently pushed into the pharyngeal cavity. Pharyngeal stimulation increased iT4 and iCT secretion, but iPTH secretion was unchanged. The secretion responses were abolished by transecting the superior laryngeal nerves (SLNs) bilaterally. The activities of the thyroid parasympathetic efferent nerves and the afferent nerves in the SLN increased significantly during pharyngeal stimulation. These results indicate that pharyngeal mechanical stimulation promotes thyroxin and calcitonin secretion from the thyroid gland by a reflex increase in SLN parasympathetic efferent activity, triggered by excitation of SLN mechanoreceptive afferents.

Age-Related Changes in Neuromodulatory Control of Bladder Micturition Contractions Originating in the Skin.

The brainstem is essential for producing micturition contractions of the urinary bladder. Afferent input from perineal skin evoked by gentle mechanical stimulation inhibits micturition contractions by decreasing both ascending and descending transmissions between the brainstem and spinal cord. Dysfunction of this inhibitory mechanism may be one cause of the increase in the prevalence of overactive bladder in old age. The aim of this study was to examine effect of aging on function of skin afferent fibers that inhibit bladder micturition contractions in rats. We used anesthetized male rats in three different age groups: young adult (4-5 months old), middle aged (6-9 months old), and aged (27-30 months old). The bladder was expanded to produce isovolumetric rhythmic micturition contractions. Skin afferent fibers were activated for 1 min either by electrical stimulation (0.5 ms, 0.2-10 V, 0.1-10 Hz) of the cutaneous branch of the pudendal nerve (CBPN) or by gentle mechanical skin stimulation with an elastomer roller. When skin afferent nerves were activated electrically, micturition contractions were inhibited in a similar manner in all age groups, with long latency inhibition induced by excitation of Aß fibers and short latency inhibition by additional Aδ and C fiber excitation (at 1-10 Hz). On the contrary, when skin afferent nerves were activated mechanically by rolling, latency of inhibition following rolling stimulation was prolonged in aged rats. Single unitary afferent nerve activity of low-threshold mechanoreceptors (LTMs) from the cutaneous nerve was recorded. The discharge rate during rolling was not significantly reduced in Aß units but was much lower in Aδ and C units in aged rats (0.4 and 0.5 Hz, respectively) than in young adult rats (3 and 7 Hz). These results suggest that the neural mechanism that inhibits bladder micturition contractions by skin afferent input is well maintained in old age, but the early inhibition by gentle skin stimulation is decreased because of reduced responses of Aδ- and C-LTMs.

Effects of a Gentle, Self-Administered Stimulation of Perineal Skin for Nocturia in Elderly Women: A Randomized, Placebo-Controlled, Double-Blind Crossover Trial.

BACKGROUND: Somatic afferent nerve stimuli are used for treating an overactive bladder (OAB), a major cause of nocturia in the elderly. Clinical evidence for this treatment is insufficient because of the lack of appropriate control stimuli. Recent studies on anesthetized animals show that gentle stimuli applied to perineal skin with a roller could inhibit micturition contractions depending on the roller's surface material. We examined the efficacy of gentle skin stimuli for treating nocturia. METHODS: The study was a cross-over, placebo-controlled, double-blind randomized clinical study using two rollers with different effects on micturition contractions. Participants were elderly women (79-89 years) with nocturia. Active (soft elastomer roller) or placebo (hard polystyrene roller) stimuli were applied to perineal skin by participants for 1 min at bedtime. A 3-day baseline assessment period was followed by 3-day stimulation and 4-day resting periods, after which the participants were subjected to other stimuli for another 3 days. The primary outcome was change in the frequency of nighttime urination, for which charts were maintained during each 3-day period. RESULTS: Twenty-four participants were randomized, of which 22 completed all study protocols. One participant discontinued treatment because of an adverse event (abdominal discomfort). In participants with OAB (n = 9), change from baseline in the mean frequency of urination per night during the active stimuli period (mean ± standard deviation, -0.74 ± 0.7 times) was significantly greater than that during placebo stimuli periods (-0.15 ± 0.8 times [p < 0.05]). In contrast, this difference was not observed in participants without OAB (n = 13). CONCLUSIONS: These results suggest that gentle perineal stimulation with an elastomer roller is effective for treating OAB-associated nocturia in elderly women. Here the limitation was a study period too short to assess changes in the quality of sleep and life. TRIAL REGISTRATION: UMIN Clinical Trial Registry (CTR) UMIN000015809.