Activation Of Afferent Fibers Research Articles

Modelling of impulse activity of afferent fibers of antagonist muscles during transcutaneous electrical stimulation of the spinal cord during walking

The article describes the results of studies on the impulse activity of various groups of afferent fibers and EMG patterns of lower leg antagonist muscles when walking without, during and after transcutaneous electrical stimulation of the dorsal roots of the lower thoracic spinal cord of a person. Using a mathematical model based on the prediction of the triggering of muscle spindles, variability in the manifestation of impulse activity of various afferents tibialis anterior muscle (TA) and gastrocnemius medialis muscle (GM) when walking under different experimental conditions is shown. It was found that walking on a movable treadmill tape in the absence of spinal cord stimulation was accompanied by strong impulse activity of afferents I (Ia and Ib) and II groups GM, increased excitability of its motorneuron pool and weakening of afferent activity and excitability of TA. On the contrary, electrical stimulation of the spinal cord during walking caused strong impulsive activity of group II TA afferents and moderate — GM, while the activity of Ia fibers TA and GM decreased to moderate impulsivity, Ib afferents of the same muscles had the weakest activity, and the excitability of the GM motorneuron pool was greater than TA. During the postactivation period, walking was accompanied by increased impulses of afferent fibers of group Ib and II GM, weakening of afferent flows of Ib TA and Ia afferents GM, but along with this, afferent signals of group Ia and II to the motorneuron nucleus TA decreased to moderate impulses, and excitability of the motorneuron pool GM was higher than TA. The supposed reflex mechanisms of locomotion regulation are discussed on the basis of well-known phenomena associated with the interaction of various afferent inputs to the spinal cord neuronal apparatus in the system of lower leg antagonist muscles.

Nodose afferent fibers require PIEZO2 for esophageal mechanosensation

The esophagus receives dual innervation of extrinsic afferent fibers from both the dorsal root ganglia as well as the vagal ganglia. These are polymodal sensory afferents that are able to sense a variety of stimuli that include chemical and mechanical stimuli. Previous research has demonstrated that the esophagus is innervated by low threshold mechanoreceptors arising from the nodose ganglia, which provide critical peripheral feedback that is required for proper swallowing and peristaltic reflexes. We know that in the vagal system, PIEZO2 plays a critical role in lung inflation and baroreceptor function in the aorta and carotid sinus. Hence, we hypothesize that PIEZO2 is the mechanotransducer in these nodose esophageal low threshold mechanoreceptors. We used a two-pronged approach to elucidate PIEZO2’s role in esophageal mechanosensation: first, GCaMP6s imaging and then single fiber electrophysiology to understand the kinetics of nodose esophageal afferent fiber activation. Both of these approaches used our ex-vivo intact vagal esophageal preparation. Our proof-of-principle studies were conducted in PIRT-GCaMP6s mice, obtained through the crossbreeding of Pirt-Cre (Cre expressed in all sensory neurons) mice with Cre-dependent, ROSA26 based, GCaMP6s reporter (B6.129S6-Gt(ROSA)26Sor-tm96(CAG-CGaMP6s)Hze). Our preliminary data in Pirt-GCaMP6s mice showed a profound increase in the Ca2+ influx in a subset of nodose neurons in response to mechanical distention of the esophagus at 5, 10, and 30mmHg pressures. For our knockout group, we obtained nodose-specific knockout of PIEZO2 by crossing P2X2-Cre mice (P2X2 is expressed in all nodose neurons) with PIEZO2fl/fl mice (P2X2/PIEZO2 KO mice). Upon performing our GCaMP6s imaging experiments in this group, we saw that there was a significant reduction in the number of nodose neurons that were responsive to esophageal distention (58% down to 17%). Comparing the fluorescence intensities of all esophageal neurons between the control and KO groups, we observed a significant reduction at all three intraesophageal pressures (p<0.05, n=458 and 395 neurons in control and KO groups, respectively). In our single fiber electrophysiology experiments, our control and KO groups were PIEZO2fl/fl mice and P2X2/PIEZO2 KO respectively. We were able to successfully record APs from A-fiber mechanosensitive esophageal neurons. The number of APs recorded from KO group was reduced at all the three intraesophageal pressures when compared to the control PIEZO2fl/fl mice. Our findings support the hypothesis that PIEZO2 is the mechanotransduction protein involved in vagal nodose afferent fibers innervating the esophagus. NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects and mechanisms of acupuncture analgesia mediated by afferent nerves in acupoint microenvironments.

In the past few decades, the use of acupuncture analgesia in clinical practice has increased worldwide. This is due to its various benefits, including natural alleviation of pain without causing various adverse effects associated with non-steroidal anti-inflammatory drugs (NSAID) and opioids. The acupoint represents the initial site of acupuncture stimulation, where diverse types of nerve fibers located at the acupoint hold significant roles in the generation and transmission of acupuncture-related information. In this study, we analyzed the patterns and mechanisms of acupuncture analgesic mediated by acupoint afferent fibers, and found that acupuncture stimulates acupoints which rapidly and directly induces activation of high-density primary afferent fibers under the acupoints, including myelinated A fibers and unmyelinated C fibers. During acupuncture stimulation at the muscle layer, the analgesic effects can be induced by stimulation of A fiber threshold intensity. At the skin layer, the analgesic effects can only be produced by stimulation of C fiber threshold intensity. Electroacupuncture (EA) activates A fibers, while manual acupuncture (MA) activates both A and C fibers. Furthermore, acupuncture alters acupoint microenvironments, which positively modulates afferent fibers, enhancing the transmission of analgesic signals. In addition to local activation and conduction at acupoints, nerve fibers mediate the transmission of acupuncture information to pain centers. In the spinal cord, acupuncture activates neurons by inducing afferent fiber depolarization, modulating pain gating, inhibiting long-term potentiation (LTP) of the spinal dorsal horn and wide dynamic range (WDR) neuronal activities. At higher nerve centers, acupuncture inhibits neuronal activation in pain-related brain regions. In summary, acupuncture inhibits pain signal transmission at peripheral and central systems by activating different patterns of afferent fibers located on various layers of acupoints. This study provides ideas for enhancing the precise application and clinical translation of acupuncture.

Selective neural inhibition via photobiomodulation alleviates behavioral hypersensitivity associated with small sensory fiber activation.

Photobiomodulation at higher irradiances has great potential as a pain-alleviating method that selectively inhibits small diameter nerve fibers and corresponding sensory experiences, such as nociception and heat sensation. The longevity and magnitude of these effects as a function of laser irradiation parameters at the nerve was explored. In a rodent chronic pain model (spared nerve injury-SNI), light was applied directly at the sural nerve with four delivery schemes: two irradiance levels (7.64 and 2.55 W/cm2 ) for two durations each, corresponding to either 4.8 or 14.4 J total energy, and the effect on sensory hypersensitivities was evaluated. At emitter irradiances of 7.64 W/cm2 (for 240 s), 2.55 W/cm2 (for 720 s), and 7.64 W/cm2 (for 80 s) the heat hypersensitivity was relieved the day following photobiomodulation (PBM) treatment by 37 ± 8.1% (statistically significant, p < 0.001), 26% ± 6% (p = 0.072), and 28 ± 6.1% (statistically significant, p = 0.032), respectively, and all three treatments reduced the hypersensitivity over the course of the experiment (13 days) at a statistically significant level (mixed-design analysis of variance, p < 0.05). The increases in tissue temperature (5.3 ± 1.0 and 1.3 ± 0.4°C from 33.3°C for the higher and lower power densities, respectively) at the neural target were well below those typically associated with permanent action potential disruption. The data from this study support the use of direct PBM on nerves of interest to reduce sensitivities associated with small-diameter fiber activity.

Selective recording of physiologically evoked neural activity in a mixed autonomic nerve using a minimally invasive array.

Real-time closed-loop control of neuromodulation devices requires long-term monitoring of neural activity in the peripheral nervous system. Although many signal extraction methods exist, few are both clinically viable and designed for extracting small signals from fragile peripheral visceral nerves. Here, we report that our minimally invasive recording and analysis technology extracts low to negative signal to noise ratio (SNR) neural activity from a visceral nerve with a high degree of specificity for fiber type and class. Complex activity was recorded from the rat pelvic nerve that was physiologically evoked during controlled bladder filling and voiding, in an extensively characterized in vivo model that provided an excellent test bed to validate our technology. Urethane-anesthetized male rats (n = 12) were implanted with a four-electrode planar array and the bladder instrumented for continuous-flow cystometry, which measures urodynamic function by recording bladder pressure changes during constant infusion of saline. We demonstrated that differential bipolar recordings and cross-correlation analyses extracts afferent and efferent activity, and discriminated between subpopulations of fibers based on conduction velocity. Integrated Aδ afferent fiber activity correlated with bladder pressure during voiding (r2: 0.66 ± 0.06) and was not affected by activating nociceptive afferents with intravesical capsaicin (r2: 0.59 ± 0.14, P = 0.54, and n = 3). Collectively, these results demonstrate our minimally invasive recording and analysis technology is selective in extracting mixed neural activity with low/negative SNR. Furthermore, integrated afferent activity reliably correlates with bladder pressure and is a promising first step in developing closed-loop technology for bladder control.

IL-1R mediated renal sensory nerve activity drives hypertension in the DOCA-Salt mouse

Clinical trials of renal denervation (RDN) have shown unanticipated changes in non-renal sympathetic activity. It has been hypothesized that this is due to ablation of sympathoexcitatory afferent renal nerves, which are overactive under conditions of renal inflammation. This study sought to investigate the interaction of the inflammatory cytokine, IL-1, and afferent renal nerves in the pathogenesis of hypertension. To test this hypothesis, we compared the effect of afferent RDN (ARDN) to the administration of the IL-1R antagonist anakinra, on the pathogenesis DOCA-salt hypertension. In addition, the combination of ARDN and anakinra treatments in DOCA-salt mice was administered to assess the degree of mechanistic overlap. 10-week-old male C57BL6/J mice were implanted with radio-telemetry probes in the carotid artery for measurement of mean arterial pressure (MAP). DOCA was administered via subcutaneous implantation of a silicon pellet containing 50 mg of DOCA. Sham mice received a drug free silicon pellet. Uni-nephrectomy, pellet insertion, salt treatment, ARDN were all performed or started on the same day. ARDN was performed through peri-axonal application of capsaicin. IL-1R antagonist anakinra was used to suppress activation of IL-1R. Anakinra (75mg/kg) was delivered via intraperitoneal injection daily 10 days post induction of hypertension. Animals in the untreated or monotherapy groups received sham RDN and/or vehicle injections. Baseline MAP was measured 3 days prior to induction of DOCA-salt hypertension by radiotelemetry. MAP increased in untreated DOCA-salt mice by 42 ± 2 mmHg (n=7) from baseline in the final week of the study. In comparison, this response was attenuated by 42% by ARDN (+24 ± 2 mmHg, n=7). IL-1α and IL-1β were both increased in DOCA-salt kidneys (112.4 ± 19.2 pg/mg and 2.1 ± 0.4 pg/mg respectively) compared to sham kidneys (31.98 ± 4.4 pg/mg and 0.36 ± 0.06 pg/mg respectively). The DOCA-salt induced increase of MAP in mice treated with anakinra alone (+23 ± 3 mmHg, n=9), or the combination of ARDN and anakinra (+26 ± 3 mmHg, n=5) was similar to ARDN monotherapy (+24 ± 2 mmHg, n=7). All treatment groups showed statistically significant changes in MAP compared to the SHAM and Vehicle treated group with 2 Way ANOVA and Tukey test for multiple comparisons. The finding that ARDN and anakinra combination therapy provides no additional benefit beyond ARDN or anakinra alone, suggests a common mechanism. We propose that antagonism of IL-1R blocks IL-1 mediated activation of afferent renal nerves resulting in decreased central sympathetic tone and decreased MAP. Further investigation into the mechanisms of cytokine mediated sensory fiber activation in the kidney are the subject of ongoing studies. T32DK083250-01A1, R01HL116476 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Constitutive Expression of Hif2α Confers Acute O2 Sensitivity to Carotid Body Glomus Cells.

Acute oxygen (O2) sensing and adaptation to hypoxia are essential for physiological homeostasis. The prototypical acute O2 sensing organ is the carotid body, which contains chemosensory glomus cells expressing O2-sensitive K+ channels. Inhibition of these channels during hypoxia leads to cell depolarization, transmitter release, and activation of afferent sensory fibers terminating in the brain stem respiratory and autonomic centers. Focusing on recent data, here we discuss the special sensitivity of glomus cell mitochondria to changes in O2 tension due to Hif2α-dependent expression of several atypical mitochondrial electron transport chain subunits and enzymes. These are responsible for an accelerated oxidative metabolism and the strict dependence of mitochondrial complex IV activity on O2 availability. We report that ablation of Epas1 (the gene coding Hif2α) causes a selective downregulation of the atypical mitochondrial genes and a strong inhibition of glomus cell acute responsiveness to hypoxia. Our observations indicate that Hif2α expression is required for the characteristic metabolic profile of glomus cells and provide a mechanistic explanation for the acute O2 regulation of breathing.

Nonlinear Model Predictive Control of Vagal Nerve Stimulation to regulate hemodynamic variables

Various pre-clinical investigations indicate that the electrical stimulation of the cervical branch of the vagus that innervates the heart has therapeutic value in the management of various cardiac diseases. In theory, the design of a closed-loop control mechanism that automatically adjusts vagal nerve stimulation (VNS) parameters based on real-time physiological feedback can eliminate intra-patient variability in VNS outcomes and therefore represents a major step towards patient-specific therapy. This study develops a nonlinear model predictive control (NMPC) approach for VNS of a pulsatile, human cardio-baroreflex system. The manipulated variables are the frequency and amplitude of a charge-balanced biphasic current. The effects of these variables on hemodynamic quantities such as heart rate, blood pressure, heart contractility e.t.c. are estimated under the assumption that the desired activation of efferent vagal nerve fibers within the vagosympathetic complex can not be realistically isolated from the off-target activation of afferent fibers. An approximate, cycle-averaged cardiovascular model is derived to eliminate pulsatility and is used for prediction in the controller. The feasibility of this NMPC scheme is explored with a set-point tracking example.

Neurophysiological and clinical outcome measures of the impact of electrical stimulation on spasticity in spinal cord injury: Systematic review and meta-analysis.

This systematic review and meta-analysis aims to determine whether non-invasive electrical stimulation (ES) is effective at reducing spasticity in people living with spinal cord injury (SCI). PubMed, Web of Science, Scopus and Cochrane Central Register of Controlled Trials databases were searched in April 2022. Primary outcome measures were the Ashworth scale (AS), Modified Ashworth scale (MAS), Pendulum test and the Penn spasm frequency scale (PSFS). Secondary outcomes were the Hoffman (H)- reflex, motor-evoked potentials (MEPs) and posterior-root reflexes (PRRs). A random-effects model, using two correlation coefficients, ( , ) determined the difference between baseline and post-intervention measures for RCTs. A quantitative synthesis amalgamated data from studies with no control group (non-RCTs). Twenty-nine studies were included: five in the meta-analysis and 17 in the amalgamation of non-RCT studies. Twenty studies measured MAS or AS scores, 14 used the Pendulum test and one used the PSFS. Four measured the H-reflex and no studies used MEPs or PRRs. Types of ES used were: transcutaneous electrical nerve stimulation (TENS), transcutaneous spinal cord stimulation (TSCS), functional electrical stimulation (FES) cycling and FES gait. Meta-analyses of 3 studies using the MAS and 2 using the Pendulum test were carried out. For MAS scores, non-invasive ES was effective at reducing spasticity compared to a control group (p = 0.01, ; p = 0.002, ). For Pendulum test outcomes, there was no statistically significant difference between intervention and control groups. Quantitative synthesis of non-RCT studies revealed that 22 of the 29 studies reported improvement in at least one measure of spasticity following non-invasive ES, 13 of which were statistically significant (p < 0.05). Activation of the muscle was not necessary to reduce spasticity. Non-invasive ES can reduce spasticity in people with SCI, according to MAS scores, for both RCT and non-RCT studies, and Pendulum test values in non-RCT studies. This review could not correlate between clinical and neurophysiological outcomes; we recommend the additional use of neurophysiological outcomes for future studies. The use of TSCS and TENS, which did not induce a muscle contraction, indicate that activation of afferent fibres is at least required for non-invasive ES to reduce spasticity.

Trigeminal afferents sense locomotion-related meningeal deformations.

The trigeminal sensory innervation of the cranial meninges is thought to serve a nociceptive function and mediate headache pain. However, the activity of meningeal afferents under natural conditions in awake animals remains unexplored. Here, we used two- and three-dimensional two-photon calcium imaging to track the activity of meningeal afferent fibers in awake mice. Surprisingly, a large subset of afferents was activated during non-noxious conditions such as locomotion. We estimated locomotion-related meningeal deformations and found afferents with distinct dynamics and tuning to various levels of meningeal expansion, compression, shearing, and Z-axis motion. Further, these mechanosensitive afferents were often tuned to distinct directions of meningeal expansion or compression. Thus, in addition to their role in headache-relatedpain, meningeal sensory neurons track the dynamic mechanical state of the meninges under natural conditions.

O081 / #805 MECHANISMS OF LOW FREQUENCY SUB PERCEPTION SPINAL CORD STIMULATION: TRACK 1: MECHANISMS OF ACTION, MAPPING AND SPINAL CORD STIMULATION

Spinal cord stimulation (SCS) was developed as a treatment for chronic pain based on the gate-control theory, which posits that activation of large diameter afferent fibers leads to inhibition of dorsal horn (DH) pain projection neurons. Conventional SCS uses low stimulation frequencies (<200 Hz) at amplitudes above sensory threshold to activate dorsal column (DC) axons and inhibit pain. SCS above sensory threshold generates paresthesias that some patients find undesirable, and recent subperception modalities of SCS demonstrated equivalent or superior pain relief without evoking paresthesias.

Developmental eye motion plasticity after unilateral embryonic ear removal in Xenopus laevis

SummaryGaze stabilization relies on bilateral mirror-symmetric vestibular endorgans, central circuits, and extraocular motor effectors. Embryonic removal of one inner ear before the formation of these structures was used to evaluate the extent to which motor outputs in the presence of a singular inner ear can develop. Near-congenital one-eared tadpoles subjected to separate or combinatorial visuo-vestibular motion stimulation exhibited comparable eye movements, though smaller in gain to controls, whereas isolated visuo-motor responses were unaltered. Surprisingly, vestibulo-ocular reflexes were robust during off-direction motion toward the missing ear in most cases and often attenuated during on-direction motion. This bidirectional plasticity of signal encoding appears to occur at the expense of vestibular reflexes during motion in the normally preferential activation direction of the singular ear. Consequently, formation of central vestibulo-motor circuits in one-eared animals likely relies on multi-neuronal homeostatic strategies, including enhanced afferent fiber activity in the attempt to adjust bilateral sensorimotor transformations.

Optimizing sensory fiber activation during cervical transcutaneous spinal stimulation using different electrode configurations: A computational analysis.

Cervical transcutaneous spinal cord stimulation (tSCS) is a rehabilitation tool which has been used to promote upper-limb motor recovery after spinal cord injury. Importantly, optimizing sensory fiber activation at specific spinal segments could enable activity-dependent neuromodulation during rehabilitation. An anatomically realistic cervical tSCS computational model was used to analyze the activation of α-motor and Aα-sensory fibers at C7 and C8 spinal segments using nine cathode electrode configurations. Specifically, the cathode was simulated at three vertebral level positions: C6, C7, and T1; and in three sizes: 5.0 × 5.0, 3.5 × 3.5, and 2.5 × 2.5cm2 , while the anode was on the anterior neck. Finite element method was used to estimate the electric potential distribution along α-motor and Aα-sensory fibers, and computational models were applied to simulate the fiber membrane dynamics during tSCS. The minimum stimulation intensity necessary to activate the fibers (activation threshold) was estimated and compared across cathode configurations in an effort to optimize sensory fiber activation. Our results showed that nerve fibers at both C7 and C8 spinal segments were recruited at lower stimulation intensities when the cathode was positioned over the C7 or T1 vertebra compared with the C6 position. Sensory fibers were activated at lower stimulation intensities using smaller electrodes, which could also affect the degree of nerve fiber activation across different positions. Importantly, Aα-sensory fibers were consistently recruited before α-motor fibers. These results imply that cathode positioning could help optimize preferential activation of hand muscles during cervical tSCS.

Vagus nerve stimulated by microbiota-derived hydrogen sulfide mediates the regulation of berberine on microglia in transient middle cerebral artery occlusion rats.

Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut-brain axis signals in berberine-modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H2 S) metabolism, and cysteine persulfides of transient receptor potential vanilloid 1 (TRPV1) receptor. The cerebral microenvironment feature was explored with a metabolomics assay. The data indicated that berberine ameliorated behavioral deficiency in transient middle cerebral artery occlusion rats through modulating microglia polarization and neuroinflammation depending on microbiota. Enhanced vagus nerve activity following berberine treatment was blocked by antibiotic cocktails, capsazepine, or sodium molybdate, respectively. Berberine-induced H2 S production was responsible for vagus nerve stimulation achieved through assimilatory and dissimilatory sulfate reduction with increased synthetic enzymes. Sulfation of the TRPV1 receptor resulted in vagus nerve activation and promoted the c-fos and ChAT in the nucleus tractus solitaries with berberine. Sphingolipid metabolism is the primary metabolic characteristic with berberine in the cerebral cortex, hippocampus, and cerebral spinal fluid disrupted by antibiotics. Berberine, in conclusion, modulates microglia polarization in a microbiota-dependent manner. H2 S stimulates the vagus nerve through TRPV1 is responsible for the berberine-induced gut-brain axis signal transmission. Sphingolipid metabolism might mediate the neuroinflammation amelioration following vagus afferent fiber activation.

Preferential activation of proprioceptive and cutaneous sensory fibers compared to motor fibers during cervical transcutaneous spinal cord stimulation: a computational study

Objective. Cervical transcutaneous spinal cord stimulation (tSCS) is a promising technology that can support motor function recovery of upper-limbs after spinal cord injury. Its efficacy may depend on the ability to recruit sensory afferents, conveying excitatory inputs onto motoneurons. Therefore, understanding its physiological mechanisms is critical to accelerate its development towards clinical applications. In this study, we used an anatomically realistic cervical tSCS computational model to compare α-motor, Aα-sensory, and Aβ-sensory fiber activation thresholds and activation sites. Approach. We developed a 3D geometry of the cervical body and tSCS electrodes with a cathode centred at the C7 spinous process and an anode placed over the anterior neck. The geometrical model was used to estimate the electric potential distributions along motor and sensory fiber trajectories at the C7 spinal level using a finite element method. We implemented dedicated motor and sensory fiber models to simulate the α-motor and Aα-sensory fibers using 12, 16, and 20 µm diameter fibers, and Aβ-sensory fibers using 6, 9, and 12 µm diameter fibers. We estimated nerve fiber activation thresholds and sites for a 2 ms monophasic stimulating pulse and compared them across the fiber groups. Main results. Our results showed lower activation thresholds of Aα- and Aβ-sensory fibers compared with α-motor fibers, suggesting preferential sensory fiber activation. We also found no differences between activation thresholds of Aα-sensory and large Aβ-sensory fibers, implying their co-activation. The activation sites were located at the dorsal and ventral root levels. Significance. Using a realistic computational model, we demonstrated preferential activation of dorsal root Aα- and Aβ-sensory fibers compared with ventral root α-motor fibers during cervical tSCS. These findings suggest high proprioceptive and cutaneous contributions to neural activations during cervical tSCS, which inform the underlying mechanisms of upper-limb functional motor recovery.

Feeding and Manual Brushing Influence the Release of Oxytocin, ACTH and Cortisol Differently During Milking in Dairy Cows.

AimThis study aimed to examine the effects of feeding or abdominal brushing on the release of the hormones oxytocin, ACTH and cortisol during milking in dairy cows.MethodsTwelve cows in early lactation were used (2 × 2 factorial experimental design), testing the effects of two types of sensory stimulation during milking over a 3 day period; feeding concentrate or manual abdominal brushing (1 stroke/s). Blood samples for hormone analyses were collected at time at −15, −1, 0 (onset of cluster), every min for 8 min, at 10, 12, 14, 16, 30, and 60 min. Hormone levels were assayed and AUC was calculated.ResultsMilking was associated with an immediate and significant rise of oxytocin. When milking was combined with feeding, significantly higher levels of oxytocin were observed at 2 and 4 mins (p < 0.05). No effect of brushing on oxytocin levels was observed. Milking alone was associated with a significant rise of ACTH levels. Feeding in connection with milking reduced the immediate rise of ACTH levels (p < 0.05) and AUC (p < 0.02), whereas no effects of brushing were found. Milking caused a progressive rise of cortisol levels. Concomitant feeding did not influence cortisol levels, whereas brushing significantly decreased cortisol levels at 1, 5 and 14 mins after onset of milking (p < 0.05).ConclusionFeeding increases oxytocin release in response to milking and decreases ACTH levels. Abdominal brushing did not influence these variables, but decreased cortisol levels. These data demonstrate that activation of afferent vagal nerve fibres and of cutaneous sensory nerves originating from the abdominal skin in front of the udder influence milking related hormone release differently.

Spinal Reflex Control of Arterial Blood Pressure: The Role of TRP Channels and Their Endogenous Eicosanoid Modulators.

The spinal cord is an important integrative center for blood pressure control. Spinal sensory fibers send projections to sympathetic preganglionic neurons of the thoracic spinal cord and drive sympathetically-mediated increases in blood pressure. While these reflexes responses occur in able-bodied individuals, they are exaggerated following interruption of descending control – such as occurs following spinal cord injury. Similar reflex control of blood pressure may exist in disease states, other than spinal cord injury, where there is altered input to sympathetic preganglionic neurons. This review primarily focuses on mechanisms wherein visceral afferent information traveling via spinal nerves influences sympathetic nerve activity and blood pressure. There is an abundance of evidence for the widespread presence of this spinal reflex arch originating from virtually every visceral organ and thus having a substantial role in blood pressure control. Additionally, this review highlights specific endogenous eicosanoid species, which modulate the activity of afferent fibers involved in this reflex, through their interactions with transient receptor potential (TRP) cation channels.

Influence of Spine Curvature on the Efficacy of Transcutaneous Lumbar Spinal Cord Stimulation.

Transcutaneous spinal cord stimulation is a non-invasive method for neuromodulation of sensorimotor function. Its main mechanism of action results from the activation of afferent fibers in the posterior roots—the same structures as targeted by epidural stimulation. Here, we investigated the influence of sagittal spine alignment on the capacity of the surface-electrode-based stimulation to activate these neural structures. We evaluated electromyographic responses evoked in the lower limbs of ten healthy individuals during extension, flexion, and neutral alignment of the thoracolumbar spine. To control for position-specific effects, stimulation in these spine alignment conditions was performed in four different body positions. In comparison to neutral and extended spine alignment, flexion of the spine resulted in a strong reduction of the response amplitudes. There was no such effect on tibial-nerve evoked H reflexes. Further, there was a reduction of post-activation depression of the responses to transcutaneous spinal cord stimulation evoked in spinal flexion. Thus, afferent fibers were reliably activated with neutral and extended spine alignment. Spinal flexion, however, reduced the capacity of the stimulation to activate afferent fibers and led to the co-activation of motor fibers in the anterior roots. This change of action was due to biophysical rather than neurophysiological influences. We recommend applying transcutaneous spinal cord stimulation in body positions that allow individuals to maintain a neutral or extended spine.

Psychological stress induced bladder overactivity in female mice is associated with enhanced afferent nerve activity

Psychological stress has been linked to the development and exacerbation of overactive bladder symptoms, as well as afferent sensitisation in other organ systems. Therefore, we aimed to investigate the effects of water avoidance stress on bladder afferent nerve activity in response to bladder filling and pharmaceutical stimulation with carbachol and ATP in mice. Adult female C57BL/6J mice were exposed to either water avoidance stress (WAS) for 1 h/day for 10 days or normal housing conditions. Voiding behaviour was measured before starting and 24-h after final stress exposure and then animals were euthanised to measure afferent nerve activity in association with bladder compliance, spontaneous phasic activity, contractile responses, as well as release of urothelial mediators. WAS caused increased urinary frequency without affecting urine production. The afferent nerve activity at low bladder pressures (4–7 mmHg), relevant to normal physiological filling, was significantly increased after stress. Both low and high threshold nerves demonstrated enhanced activity at physiological bladder pressures. Urothelial ATP and acetylcholine release and bladder compliance were unaffected by stress as was the detrusor response to ATP (1 mM) and carbachol (1 µM). WAS caused enhanced activity of individual afferent nerve fibres in response bladder distension. The enhanced activity was seen in both low and high threshold nerves suggesting that stressed animals may experience enhanced bladder filling sensations at lower bladder volumes as well as increased pain sensations, both potentially contributing to the increased urinary frequency seen after stress.

Estrogen augmented visceral pain and colonic neuron modulation in a double-hit model of prenatal and adult stress.

BACKGROUNDChronic stress during pregnancy may increase visceral hyperalgesia of offspring in a sex-dependent way. Combining adult stress in offspring will increase this sensitivity. Based on the evidence implicating estrogen in exacerbating visceral hypersensitivity in female rodents in preclinical models, we predicted that chronic prenatal stress (CPS) + chronic adult stress (CAS) will maximize visceral hyperalgesia; and that estrogen plays an important role in colonic hyperalgesia.AIMThe aim was to illuminate the role of estrogen in colonic hyperalgesia and its underlying mechanisms.METHODSWe established a CPS plus CAS rodent model in which the balloon was used to distend the colorectum. The single-fiber recording in vivo and patch clamp experiments in vitro were used to monitor the colonic neuron’s activity. The reverse transcription-polymerase chain reaction, western blot, and immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent sensitivity. We used ovariectomy and letrozole to reduce estrogen levels of female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent sensitization.RESULTSSpontaneous activity and single fiber activity were significantly greater in females than in males. The enhanced sensitization in female rats mainly came from low-threshold neurons. CPS significantly increased single-unit afferent fiber activity in L6-S2 dorsal roots in response. Activity was further enhanced by CAS. In addition, the excitability of colon-projecting dorsal root ganglion (DRG) neurons increased in CPS + CAS rats and was associated with a decrease in transient A-type K+ currents. Compared with ovariectomy, treatment with the aromatase inhibitor letrozole significantly reduced estrogen levels in female rats, confirming the gender difference. Moreover, mice treated with letrozole had decreased colonic DRG neuron excitability. The intrathecal infusion of estrogen increased brain-derived neurotrophic factor (BDNF) protein levels and contributed to the response to visceral pain. Western blotting showed that nerve growth factor protein was upregulated in CPS + CAS mice.CONCLUSIONThis study adds to the evidence that estrogen-dependent sensitization of primary afferent colon neurons is involved in the development of chronic stress-induced visceral hypersensitivity in female rats.