Somatic Afferent Stimulation Research Articles

Transcutaneous electrical stimulation of somatic afferent nerves in the foot relieved symptoms related to postoperative bladder spasms

BackgroundBladder spasm is a common side effect of urological surgery. Main treatment modalities include opioids or anticholinergic medication; however, bladder spasms still occur even after these interventions. Recent studies indicate that transcutaneous stimulation of the foot can result in 50% increase in bladder capacity in healthy adults, and inhibit bladder detrusor overactivity in spinal cord injured patients. In this study, we examined the effects of transcutaneous electrical stimulation of the foot on bladder spasms related symptoms.MethodsSixty-six male patients who underwent prostate or bladder surgeries due to benign prostatic hyperplasia or bladder diseases were randomly divided into two groups: the control group (n = 36) and the treatment group (n = 30). The control group received the routine postoperative care. The treatment group received daily transcutaneous electrical stimulation of the foot during 3 days after surgery; each time lasted for 60 min. All patients were evaluated by the Visual Analogue Scale for pain sensation, frequency of bladder spasm episodes, and a total score of bladder spasms symptoms.ResultsIn the control group, the patients with bladder surgery had a higher Visual Analogue Scale score than patients with prostate surgery (P = 0.024). In both treatment and control groups, the Visual Analogue Scale score, spasm frequency, and total score of bladder spasm symptoms decreased from day 1 to day 3 (P <0.001). The Visual Analogue Scale score at day 2, total score of bladder spasm symptoms at day 2 and day 3 were significantly lower in the treatment group than in the control group (P <0.05).ConclusionThese results provided preliminary evidence suggesting beneficial effects of stimulating somatic afferent nerves in the foot on postoperative bladder spasms.Trial registrationThe study was registered with Chinese Clinical Trial Registry on June 13 2016 (http://www.chictr.org.cn/) (Identifier: ChiCTR-INR-16008635)

Sciatic nerve stimulation activates the retrotrapezoid nucleus in anesthetized rats.

Retrotrapezoid nucleus (RTN) neurons sustain breathing automaticity. These neurons have chemoreceptor properties, but their firing is also regulated by multiple synaptic inputs of uncertain function. Here we test whether RTN neurons, like neighboring presympathetic neurons, are excited by somatic afferent stimulation. Experiments were performed in Inactin-anesthetized, bilaterally vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats. End-expiratory CO2 (eeCO2) was varied between 4% and 10% to modify rate and amplitude of phrenic nerve discharge (PND). RTN and presympathetic neurons were recorded extracellularly below the facial motor nucleus with established criteria. Sciatic nerve stimulation (SNstim, 1 ms, 0.5 Hz) slightly increased blood pressure (6.6 ± 1.6 mmHg) and heart rate and, at low eeCO2 (<5.5%), entrained PND. Ipsi- and contralateral SNstim produced the known biphasic activation of presympathetic neurons. SNstim evoked a similar but weaker biphasic response in up to 67% of RTN neurons and monophasic excitation in the rest. At low eeCO2, RTN neurons were silent and responded more weakly to SNstim than at high eeCO2 RTN neuron firing was respiratory modulated to various degrees. The phasic activation of RTN neurons elicited by SNstim was virtually unchanged at high eeCO2 when PND entrainment to the stimulus was disrupted. Thus RTN neuron response to SNstim did not result from entrainment to the central pattern generator. Overall, SNstim shifted the relationship between RTN firing and eeCO2 upward. In conclusion, somatic afferent stimulation increases RTN neuron firing probability without altering their response to CO2. This pathway may contribute to the hyperpnea triggered by nociception, exercise (muscle metabotropic reflex), or hyperthermia.

Paraventricular Nucleus Modulates Excitatory Cardiovascular Reflexes during Electroacupuncture.

The paraventricular nucleus (PVN) regulates sympathetic outflow and blood pressure. Somatic afferent stimulation activates neurons in the hypothalamic PVN. Parvocellular PVN neurons project to sympathoexcitatory cardiovascular regions of the rostral ventrolateral medulla (rVLM). Electroacupuncture (EA) stimulates the median nerve (P5-P6) to modulate sympathoexcitatory responses. We hypothesized that the PVN and its projections to the rVLM participate in the EA-modulation of sympathoexcitatory cardiovascular responses. Cats were anesthetized and ventilated. Heart rate and mean blood pressure were monitored. Application of bradykinin every 10-min on the gallbladder induced consistent pressor reflex responses. Thirty-min of bilateral EA stimulation at acupoints P5-P6 reduced the pressor responses for at least 60-min. Inhibition of the PVN with naloxone reversed the EA-inhibition. Responses of cardiovascular barosensitive rVLM neurons evoked by splanchnic nerve stimulation were reduced by EA and then restored with opioid receptor blockade in the PVN. EA at P5-P6 decreased splanchnic evoked activity of cardiovascular barosensitive PVN neurons that also project directly to the rVLM. PVN neurons labeled with retrograde tracer from rVLM were co-labeled with μ-opioid receptors and juxtaposed to endorphinergic fibers. Thus, the PVN and its projection to rVLM are important in processing acupuncture modulation of elevated blood pressure responses through a PVN opioid mechanism.

Serotonin release in the central nucleus of the amygdala in response to noxious and innocuous cutaneous stimulation in anesthetized rats.

We investigated the effect of noxious (pinching) and innocuous (stroking) stimulation of skin on serotonin (5-HT) release in the central nucleus of the amygdala (CeA) in anesthetized rats. 5-HT in the CeA was collected by microdialysis methods. Dialysate output from consecutive 10-min periods was injected into a high-performance liquid chromatograph and 5-HT was measured with an electrochemical detector. Bilateral pinching of the back for 10min increased 5-HT release significantly; 5-HT release was also increased with stimulation of the forelimb or hindlimb. In contrast, stroking of these areas decreased 5-HT release significantly. Furthermore, simultaneous stroking and pinching produced no change in the 5-HT release. In conclusion, the present study demonstrates that 5-HT release in the CeA is regulated by somatic afferent stimulation in a modality-dependent manner, and that innocuous stimulation can dampen the change in 5-HT release that occurs in response to noxious stimulation.

Effect of acupuncture-like stimulation on cortical cerebral blood flow in aged rats.

This study aimed to examine the effect of acupuncture-like stimulation on cortical cerebral blood flow (CBF) in aged rats and the contribution of the intracranial cholinergic vasodilatory system on its response. In urethane-anesthetized rats of 30-37 months of age, manual acupuncture-like stimulation of a forepaw produced an increase in the CBF, independent of systemic arterial pressure. The increase in the CBF induced by forepaw stimulation was abolished by intravenous administration of cholinergic receptor antagonists. Manual acupuncture-like stimulation of a forepaw increased extracellular acetylcholine release in the cerebral cortex. These results suggest that natural somatic afferent stimulation, such as acupuncture-like stimulation, activates the intracranial - most likely, basal forebrain - cholinergic vasodilatory system in the cerebral cortex, even in extremely aged rats.

Autonomic nervous regulation of ovarian function by noxious somatic afferent stimulation.

It is well known that ovarian function is regulated by hypothalamic–pituitary–ovarian hormones. However, although several histological studies have described the autonomic innervation of the ovary, the involvement of these autonomic nerves in ovarian function is unclear. Recently, it has been shown that both the superior ovarian nerve (SON) and the ovarian nerve plexus (ONP) induce vasoconstrictor activity by activation of alpha 1-adrenoceptors, whereas the SON, but not the ONP, inhibits ovarian estradiol secretion by activation of alpha 2-adrenoceptors. Furthermore, reflex activation of these ovarian nerves by noxious cutaneous stimulation of the rat hindpaw results in ovarian vasoconstriction and inhibition of estradiol secretion. Thus, in addition to long-term regulation of ovarian function by hormones, ovarian autonomic innervation may be involved in rapid regulation of ovarian function by responding to either internal or external environmental changes.

Electrical Stimulation of Somatic Afferent Nerves in the Foot Increases Bladder Capacity in Healthy Human Subjects

We determined whether electrical stimulation of somatic afferent nerves in the foot could delay bladder filling sensations and increase bladder capacity in healthy humans without overactive bladder. Eight subjects underwent 90-minute foot stimulation using skin surface electrodes connected to a transcutaneous electrical nerve stimulator. The electrodes were attached to the bottom of the foot. Subjects completed a 3-day voiding diary, during which foot stimulation was applied on day 2. Stimulation parameters were pulse frequency 5 Hz, rectangular waveform pulse width 0.2 milliseconds and intensity 2 to 6 times the minimal stimulation current necessary to induce toe twitch. Stimulation intensity was set by each subject to a maximal level without causing discomfort. Subjects were provided with 500 to 1,000 ml of water to drink during stimulation. Average ± SE volume per void was 350 ± 22 ml during the 24 hours before foot stimulation. This voided volume increased to a mean of 547 ± 52 ml for up to 5 hours after stimulation (p <0.01). Average voided volume returned to 363 ± 21 ml within 36 hours after stimulation. There were no adverse events. Foot stimulation can delay bladder filling sensations and significantly increase bladder capacity in healthy humans without overactive bladder. Although the study group was small, our results support moving forward with clinical trials of foot neuromodulation in patients with overactive bladder.

PARAVENTRICULAR NUCLEUS CONTRIBUTES TO ACUPUNCTURE MODULATION OF SYMPATHOEXCITATORY CARDIOVASCULAR REFLEXES

The paraventricular nucleus (PVN) regulates sympathetic outflow and blood pressure (BP). Somatic afferent stimulation activates PVN neurons that project directly to the rostral ventrolateral medulla (rVLM), but little is known about the physiological actions and regulation of its neural activity. Since electroacupuncture (EA) stimulates somatic nerves to modulate sympathoexcitatory reflex responses, we hypothesized that the PVN and its projections to the rVLM participate in the sympathoexcitatory cardiovascular actions of EA. Cats were anesthetized, ventilated, and heart rate and BP monitored. Bradykinin (BK) applied every 10 min to the gallbladder induced consistent pressor responses. EA at acupoints P5–6 reduced the pressor responses for 60 min. Naloxone microinjection into the PVN restored the change in BP during BK‐induced pressor responses. Retrograde tracing from the rVLM showed EA‐related c‐Fos PVN neurons juxtaposed to endorphinergic PVN fibers. EA decreased splanchnic nerve‐evoked cardiovascular PVN neurons with direct projections to the rVLM for 60 min. Responses of cardiovascular barosensitive sympathoexcitatory rVLM neurons receiving median nerve input was reduced by EA and restored by PVN naloxone blockade. Thus, sympathoexcitatory PVN responses and a naloxone sensitive PVN‐rVLM pathway contribute to central neural processing during EA. Supported by HL‐72125.

Neuromodulation in treatment of hypertension by acupuncture: A neurophysiological prospective

Hypertension is a major public health problem affecting over one billion individuals worldwide. This disease is the result of complex interactions between genetic and life-style factors and the central nervous system. Sympathetic hyperactivity has been postulated to be present in most forms of hypertension. Pharmaceutical therapy for hypertension has not been perfected, often requires a multidrug regimen, and is associated with adverse side effects. Acupuncture, a form of somatic afferent nerve stimulation has been used to treat a host of cardiovascular diseases such as hypertension. It has long been established that the two major contributors to systemic hypertension are the intrarenal reninangiotensin system and chronic activation of the sympathetic nervous system. A number of important studies on the baroreflex response and its response to acupuncture are discussed. The inhibitory effects of acupuncture on the rostral ventrolateral medulla (rVLM) reduces sympathetic nerve activity and blood pressure suggesting overactivity of the angiotensin system in this nucleus may play a role in the maintenance of hypertension. Our experimental studies have shown that electroacupuncture stimulation activates neurons in the arcuate nucleus, ventro-lateral gray, and nucleus raphe to inhibit the neural activity in the rVLM in a model of visceral reflex stimulation-induced hypertension. The significant role of spinal cord opioids and nociceptin are also reviewed. Although clinical studies of acupuncture to date have met some success, they are rarely scientifically robust and do not feature randomization and long-term follow up. Based on a great deal of basic scientific evidence, large trials are desperately needed to study the effects of acupuncture on the hyperensive man.

Are all spinal segments equal: intrinsic membrane properties of superficial dorsal horn neurons in the developing and mature mouse spinal cord

Neurons in the superficial dorsal horn (SDH; laminae I-II) of the spinal cord process nociceptive information from skin, muscle, joints and viscera. Most of what we know about the intrinsic properties of SDH neurons comes from studies in lumbar segments of the cord even though clinical evidence suggests nociceptive signals from viscera and head and neck tissues are processed differently. This ‘lumbar-centric' view of spinal pain processing mechanisms also applies to developing SDH neurons. Here we ask whether the intrinsic membrane properties of SDH neurons differ across spinal cord segments in both the developing and mature spinal cord. Whole cell recordings were made from SDH neurons in slices of upper cervical (C2-4), thoracic (T8-10) and lumbar (L3-5) segments in neonatal (P0-5) and adult (P24-45) mice. Neuronal input resistance (R(IN)), resting membrane potential, AP amplitude, half-width and AHP amplitude were similar across spinal cord regions in both neonates and adults (∼100 neurons for each region and age). In contrast, these intrinsic membrane properties differed dramatically between neonates and adults. Five types of AP discharge were observed during depolarizing current injection. In neonates, single spiking dominated (∼40%) and the proportions of each discharge category did not differ across spinal regions. In adults, initial bursting dominated in each spinal region, but was significantly more prevalent in rostral segments (49% of neurons in C2-4 vs. 29% in L3-5). During development the dominant AP discharge pattern changed from single spiking to initial bursting. The rapid A-type potassium current (I(Ar)) dominated in neonates and adults, but its prevalence decreased (∼80% vs. ∼50% of neurons) in all regions during development. I(Ar) steady state inactivation and activation also changed in upper cervical and lumbar regions during development. Together, our data show the intrinsic properties of SDH neurons are generally conserved in the three spinal cord regions examined in both neonate and adult mice. We propose the conserved intrinsic membrane properties of SDH neurons along the length of the spinal cord cannot explain the marked differences in pain experienced in the limbs, viscera, and head and neck.

Post-Stimulation Inhibitory Effect on Reflex Bladder Activity Induced by Activation of Somatic Afferent Nerves in the Foot

We determined whether transcutaneous electrical stimulation of somatic afferent nerves in the foot of cats would induce a post-stimulation increase in bladder capacity. In 12 α-chloralose anesthetized cats electrical stimulation (5 Hz) was applied to the skin of the hind foot for 2, 30-minute periods via dual pad electrodes attached on the plantar and dorsal surfaces (combination 1 and 2) or at 2 sites on the plantar surface (combination 1 and 3). The post-stimulation effect was examined by repeat cystometrogram after 30-minute stimulation. In the control group of 12 cats isovolumetric contractions were allowed to continue during each 30-minute period without stimulation. Stimulation inhibited isovolumetric rhythmic bladder contractions. Bladder capacity was not increased after the first 30-minute foot stimulation via electrodes 1 and 2 but it was significantly increased a mean ± SE of 47.5% ± 2.9% after the second 30-minute stimulation via electrodes 1 and 3. After inducing the post-stimulation effect the foot stimulation applied during cystometrograms via electrodes 1 and 2 or 1 and 3 elicited a further increase in bladder capacity (mean 23.26% ± 17.64% and 20.07% ± 18.59%, respectively). Results show that the transcutaneous plantar electrical stimulation of somatic afferent nerves in the foot can induce a post-stimulation increase in bladder capacity, suggesting that an intermittent stimulation pattern rather than continuous stimulation might be effective as clinical application to treat overactive bladder symptoms.

Baroreflex and somato-reflex control of blood pressure, heart rate and renal sympathetic nerve activity in the obese Zucker rat

It has been reported that the baroreflex control of heart rate (HR) and sympathetic nerve activity (SNA) is attenuated in obese Zucker rats (OZRs) compared with age-matched lean animals (LZRs). What is not known, however, is the extent to which the baroreflex control of mean arterial blood pressure (MAP) is altered in the OZR. In addition, it is not known whether the interactions of other sensory nerve inputs on autonomic control are altered in the OZR compared with the LZR. The aim of this study was to determine the baroreflex control of MAP, HR and renal SNA (RSNA) in the OZR and LZR using an open-loop baroreflex approach. In addition, the effect of brachial nerve stimulation (BNS) on the baroreflex control was determined in these animals. Age-matched, male LZRs and OZRs were anaesthetized, and the carotid baroreceptors were vascularly isolated, bilaterally. The carotid sinus pressure was increased in 20 mmHg increments from 60 to 180 mmHg using an oscillating pressure stimulus. Baroreflex function curves were constructed using a four-parameter logistic equation, and gain was calculated from the first derivative, which gave a measure of baroreceptor sensitivity, before and during BNS. The range over which the baroreflex could change MAP (28 ± 6 versus 87 ± 5 mmHg; mean ± SEM), HR (17 ± 4 versus 62 ± 11 beats min(-1)) and normalized RSNA (NormNA; 22 ± 4 versus 76 ± 11%) was significantly decreased in the OZR compared with the LZR. Likewise, the maximal gain was lower in the OZR, as follows: MAP -0.88 ± 0.22 versus -2.26 ± 0.17; HR -0.42 ± 0.18 versus -1.44 ± 0.22 beats min(-1); and NormNA -0.54 ± 0.14 versus -1.65 ± 0.30% mmHg(-1). There was no difference in the mid-point of the baroreflex curve for each variable between the OZR and LZR. However, the minimal values obtained when the baroreceptors were maximally loaded were higher in the OZR (MAP 68 ± 5 versus 53 ± 4 mmHg; HR 455 ± 7 versus 390 ± 13 beats min(-1); and NormNA -19 ± 4 versus -48 ± 8%). Brachial nerve stimulation in the LZR resulted in an upward and rightward resetting of the baroreflex control of MAP and RSNA, and abolished baroreflex control of HR. The baroreflex control of RSNA in the OZR during BNS was further attenuated and reset upwards and to the right, while the HR response was abolished. With respect to MAP, the baroreflex curve reset upwards and to the right to a point comparable with the LZR during BNS. These data show that there is an attenuated baroreflex control in the OZR and that the ability to reset to higher arterial pressure during somatic afferent nerve stimulation is similar to that in the LZR.

Aging of the autonomic nervous system and possible improvements in autonomic activity using somatic afferent stimulation

There are significant age-related changes in autonomic nervous system function that are responsible for an impaired ability to adapt to environmental or intrinsic visceral stimuli in the elderly. We review data on changes in autonomic nervous system regulation of cardiovascular and urinary function, as well as data on strategies to improve function. There are data showing alterations in peripheral and central autonomic nerve activity, and decreases in neurotransmitter receptor action that lead to diminished autonomic reactivity (e.g. blood pressure and cerebral blood flow regulation) and poorly coordinated autonomic discharge (e.g. bladder function). Simple strategies for autonomic function improvement and increasing cortical blood flow include walking and somatic afferent stimulation (e.g. stroking skin or acupuncture) to increase sympathetic, parasympathetic and central cholinergic activity.

Somatic afferent modulation of thoracic (T9-T10) spinal neurons receiving gastric mechanical input in rats

The aim was to determine whether somatic afferent fiber stimulation influences thoracic spinal neuronal activity responding to gastric distensions. Extracellular potentials of single T9-T10 spinal neurons were recorded in anesthetized male rats. Ipsilateral median and peroneal nerve afferent stimulation (MNAS, PNAS) was delivered by electrodes. Inflation of a latex balloon was used to produce gastric distension. MNAS and PNAS (1.5 mA, 50 Hz, 10 sec) altered activity of 63% and 66% of the spinal neurons excited or inhibited by gastric distension, respectively. MNAS more frequently reduced spinal neuronal activity with excitatory responses to gastric distension than did PNAS (p < 0.05). PNAS more likely increased neuronal activity with low-threshold excitatory responses to gastric distension than MNAS (p < 0.05). Peripheral somatic afferent information utilizes central pathways to modulate gastric afferent processing in T9-T10 spinal neurons. Thus, somatic afferent stimulation might be used to treat gastric pain and/or hypersensitivity.

Gentle mechanical skin stimulation inhibits the somatocardiac sympathetic: C-reflex elicited by excitation of unmyelinated C-afferent fibers

The effects of gentle mechanical skin stimulation on reflex discharges in cardiac sympathetic nerve evoked by somatic afferent stimulation were studied in anesthetized rats. Mass discharges were recorded from cardiac sympathetic efferent nerve while somatocardiac sympathetic A- and C-reflexes were elicited by single electrical stimuli to myelinated A- and unmyelinated C-afferent fibers of the tibial nerve. Continuous touch was applied to inner thigh skin with a force of 0.12 N for 10 min periods by a soft elastomer “brush” (1.1 cm in diameter with 417 microcones). When touch was applied ipsilateral to the stimulated tibial nerve, the C-reflex was inhibited by up to 40% of its pre-touch amplitude, whereas the A-reflex was unaffected. Inhibition of the C-reflex started during the touch period and lasted for 15 min after cessation of touching. Contralateral touch did not inhibit the C-reflex. The opioid receptor antagonist naloxone attenuated the C-reflex inhibition, but did not abolish it. The C-reflex inhibition was abolished after severing cutaneous nerves innervating inner thigh. We recorded unitary afferent activity from thigh branches of the saphenous nerve and found fibers excited by touch were low-threshold mechanoreceptive Aβ, Aδ and C fibers that have rapidly or slowly adapting properties. In all units tested, average discharge rates during touch period were less than 4 Hz. The results suggest that touch-induced excitation of low threshold cutaneous mechanoreceptive fibers inhibits nociceptive transmission conveyed by C-primary-afferents, via the release of both opioid and non-opioid inhibitory mediators.

Randomized Trial of Percutaneous Tibial Nerve Stimulation Versus Sham Efficacy in the Treatment of Overactive Bladder Syndrome: Results From the SUmiT Trial

The Study of Urgent PC vs Sham Effectiveness in Treatment of Overactive Bladder Symptoms (SUmiT) was a multicenter, double-blind, randomized, controlled trial comparing the efficacy of percutaneous tibial nerve stimulation to sham through 12 weeks of therapy. The improvement in global response assessment, voiding diary parameters, and overactive bladder and quality of life questionnaires was evaluated. A total of 220 adults with overactive bladder symptoms were randomized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or sham therapy. Overactive bladder and quality of life questionnaires as well as 3-day voiding diaries were completed at baseline and at 13 weeks. Subject global response assessments were completed at week 13. The 13-week subject global response assessment for overall bladder symptoms demonstrated that percutaneous tibial nerve stimulation subjects achieved statistically significant improvement in bladder symptoms with 54.5% reporting moderately or markedly improved responses compared to 20.9% of sham subjects from baseline (p <0.001). All individual global response assessment subset symptom components demonstrated statistically significant improvement from baseline to 13 weeks for percutaneous tibial nerve stimulation compared to sham. Voiding diary parameters after 12 weeks of therapy showed percutaneous tibial nerve stimulation subjects had statistically significant improvements in frequency, nighttime voids, voids with moderate to severe urgency and urinary urge incontinence episodes compared to sham. No serious device related adverse events or malfunctions were reported. This pivotal multicenter, double-blind, randomized, sham controlled trial provides level I evidence that percutaneous tibial nerve stimulation therapy is safe and effective in treating overactive bladder symptoms. The compelling efficacy of percutaneous tibial nerve stimulation demonstrated in this trial is consistent with other recently published reports and supports the use of peripheral neuromodulation therapy for overactive bladder.

Serotonergic projection from nucleus raphe pallidus to rostral ventrolateral medulla modulates cardiovascular reflex responses during acupuncture.

We have demonstrated that stimulation of somatic afferents during electroacupuncture (EA) inhibits sympathoexcitatory cardiovascular rostral ventrolateral medulla (rVLM) neurons and reflex responses. Furthermore, EA at P5-P6 acupoints over the median nerve on the forelimb activate serotonin (5-HT)-containing neurons in the nucleus raphe pallidus (NRP). The present study, therefore, examined the role of the NRP and its synaptic input to neurons in the rVLM during the modulatory influence of EA. Since serotonergic neurons in the NRP project to the rVLM, we hypothesized that the NRP facilitates EA inhibition of the cardiovascular sympathoexcitatory reflex response through activation of 5-HT1A receptors in the rVLM. Animals were anesthetized and ventilated, and heart rate and blood pressure were monitored. We then inserted microinjection and recording electrodes in the rVLM and NRP. Application of bradykinin (10 microg/ml) on the gallbladder every 10 min induced consistent excitatory cardiovascular reflex responses. Stimulation with EA at P5-P6 acupoints reduced the increase in blood pressure from 41+/-4 to 22+/-4 mmHg for more than 70 min. Inactivation of NRP with 50 nl of kainic acid (1 mM) reversed the EA-related inhibition of the cardiovascular reflex response. Similarly, blockade of 5-HT1A receptors with the antagonist WAY-100635 (1 mM, 75 nl) microinjected into the rVLM reversed the EA-evoked inhibition. In the absence of EA, NRP microinjection of dl-homocysteic acid (4 nM, 50 nl), to mimic EA, reduced the cardiovascular and rVLM neuronal excitatory reflex response during stimulation of the gallbladder and splanchnic nerve, respectively. Blockade of 5-HT1A receptors in the rVLM reversed the NRP dl-homocysteic acid inhibition of the cardiovascular and neuronal reflex responses. Thus activation of the NRP, through a mechanism involving serotonergic neurons and 5-HT1A receptors in the rVLM during somatic stimulation with EA, attenuates sympathoexcitatory cardiovascular reflexes.

Randomized Trial of Percutaneous Tibial Nerve Stimulation Versus Extended-Release Tolterodine: Results From the Overactive Bladder Innovative Therapy Trial

The Overactive Bladder Innovative Therapy trial was a randomized, multicenter, controlled study that compared the effectiveness of percutaneous tibial nerve stimulation to extended-release tolterodine. The reduction in overactive bladder symptoms along with global response assessments was evaluated. A total of 100 adults with urinary frequency were randomized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or to 4 mg daily extended-release tolterodine. Voiding diaries and an overactive bladder questionnaire were completed at baseline and at the end of therapy to compare 24-hour voiding frequency, urinary urge incontinence episodes, voids causing waking, volume voided, urgency episodes and quality of life indices. Global response assessments were completed by subjects and investigators after 12 weeks of therapy. The global response assessment demonstrated that subject assessment of overactive bladder symptoms compared to baseline was statistically significant in the percutaneous tibial nerve stimulation arm with 79.5% reporting cure or improvement compared to 54.8% of subjects on tolterodine (p = 0.01). Assessments by investigators were similar but did not reach statistical significance (p = 0.05). After 12 weeks of therapy objective measures improved similarly in both groups for reductions in urinary frequency, urge urinary incontinence episodes, urge severity and nighttime voids, as well as for improvement in voided volume. There were no serious adverse events or device malfunctions. This multicenter, randomized trial demonstrates that percutaneous tibial nerve stimulation is safe with statistically significant improvements in patient assessment of overactive bladder symptoms, and with objective effectiveness comparable to that of pharmacotherapy. Percutaneous tibial nerve stimulation may be considered a clinically significant alternative therapy for overactive bladder.

Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome

We have recently shown that polycystic ovary syndrome (PCOS) is associated with high muscle sympathetic nerve activity (MSNA). Animal studies support the concept that low-frequency electroacupuncture (EA) and physical exercise, via stimulation of ergoreceptors and somatic afferents in the muscles, may modulate the activity of the sympathetic nervous system. The aim of the present study was to investigate the effect of these interventions on sympathetic nerve activity in women with PCOS. In a randomized controlled trial, 20 women with PCOS were randomly allocated to one of three groups: low-frequency EA (n = 9), physical exercise (n = 5), or untreated control (n = 6) during 16 wk. Direct recordings of multiunit efferent postganglionic MSNA in a muscle fascicle of the peroneal nerve before and following 16 wk of treatment. Biometric, hemodynamic, endocrine, and metabolic parameters were measured. Low-frequency EA (P = 0.036) and physical exercise (P = 0.030) decreased MSNA burst frequency compared with the untreated control group. The low-frequency EA group reduced sagittal diameter (P = 0.001), while the physical exercise group reduced body weight (P = 0.004) and body mass index (P = 0.004) compared with the untreated control group. Sagittal diameter was related to MSNA burst frequency (Rs = 0.58, P < 0.005) in the EA group. No correlation was found for body mass index and MSNA in the exercise group. There were no differences between the groups in hemodynamic, endocrine, and metabolic variables. For the first time we demonstrate that low-frequency EA and physical exercise lowers high sympathetic nerve activity in women with PCOS. Thus, treatment with low-frequency EA or physical exercise with the aim to reduce MSNA may be of importance for women with PCOS.

Electro-acupuncture and physical exercise reduce mesenteric adipose tissue gene expression of sympathetic markers in rats with polycystic ovary syndrome

OBJECTIVE: Altered activity of the sympathetic nervous system has been suggested as a potential actor in polycystic ovary syndrome (PCOS) etiology. Electro-acupuncture (EA) and physical exercise has the potential to decrease high activity in sympathetic nervous system via stimulation of ergoreceptors and somatic afferents in the muscles. The aim of this study was to study sympathetic activity in adipose tissue by measuring mesenteric adipose tissue gene expression of sympathetic markers (β3-adrenergic receptor [β3-AR], nerve growth factor [NGF], low affinity p75 neurotrophin receptor [p75NTR] and neuropeptide Y [NPY]) in PCOS rats.