Primary Afferent Fibers Research Articles

Cognitive effect of passively induced kinesthetic perception associated with virtual body augmentation modulates spinal reflex

The virtual movement of an augmented body, perceived as part of oneself, forms the basis of kinesthetic perception induced by visual stimulation (KINVIS). KINVIS is a visually induced virtual kinesthetic perception that clinically suppresses spasticity. The present study hypothesized that central neural network activity during KINVIS affects subcortical neural circuits. The present study aimed to elucidate whether reciprocal and presynaptic inhibition occurs during KINVIS. Seventeen healthy participants were recruited (mean age: 27.9 ± 3.6 years), and their soleus Hoffmann-reflexes (H-reflexs) were recorded by peripheral nerve stimulation while perceiving the dorsiflexion kinesthetic illusion in the right-side foot (seated in a comfortable chair). Two control conditions were set to observe the same foot video without the kinesthetic illusion while focusing on the static foot image. Unconditioned H-reflex and two types of conditioned H-reflexes were measured: Ia (reciprocal inhibition) and D1 (presynaptic inhibition). Reciprocal Ia and D1 inhibition of the soleus muscle was significantly enhanced during the kinesthetic illusion compared to the condition without kinesthetic illusion (a post-hoc analysis using the Bonferroni test: Ia inhibition, p = 0.002; D1 inhibition, p = 0.049). This study indicates that kinesthetic illusion elicits an inhibitory effect on the monosynaptic reflex loop of Ia afferents, potentially inhibiting the hyperexcitability of the stretch reflex. These findings demonstrate that brain activity associated with visually induced kinesthetic illusions acts on spinal inhibition circuits. These insights may be valuable in clinical rehabilitation practice, specifically for the treatment of spasticity.

Influence of stimulation parameters on torque development during the combined application of electrical nerve stimulation and muscle lengthening.

This study investigated the influence of stimulation parameters on torque production when combining a brief muscle lengthening with electrical stimulation. Fifteen volunteers participated in one experimental session where two distinct stimulation modalities were compared: wide-pulse high-frequency (WPHF, pulse duration: 1ms, frequency: 100Hz), favouring afferent pathways activation, and narrow-pulse low-frequency (NPLF, pulse duration: 0.05ms, frequency: 20Hz), favouring activation of the efferent pathway. Both stimulation modalities, were applied to evoke 5-10% of maximal voluntary contraction either in isometric conditions (WPHF and NPLF) or in combination with a muscle lengthening (lengthening condition: WPHF+LEN and NPLF+LEN). The torque-time integral (TTI) during the stimulation trains and the muscle activity after the cessation of the stimulation trains (sustained EMG activity, normalized to the maximal EMG activity) were assessed and compared between the stimulation modalities and the conditions (two-way ANOVA). An interaction effect was obtained, revealing significant differences in TTI and sustained EMG activity between the WPHF+LEN and the other tested conditions (P=0.048 and P=0.044, respectively). TTI and sustained EMG activity were higher for WPHF+LEN (228.4±105.3 Nm.s and 0.085±0.070, respectively) compared to WPHF (168.4±72.9 Nm.s; 0.052±0.026), NPLF+LEN (136.4±38.9 Nm.s; 0.031±0.016) and NPLF (125.2±36.1 Nm.s; 0.028±0.015). The increased TTI during the WPHF+LEN condition suggests that the contribution of afferent pathways to the evoked torque can be enhanced with the muscle lengthening superimposition. They highlight the importance of using WPHF stimulation that already solicits Ia afferents to benefit from the cumulative afferent activation induced by the muscle lengthening to further increase torque production.

Modulation of sensory input to the spinal cord: Contribution of focal epidural polarization and of GABA released by interneurons and glial cells.

Modulation of input from primary afferent fibres has long been examined at the level of the first relays of these fibres. However, recent studies reveal that input to the spinal cord may also be modulated at the level of the very entry of afferent fibres to the spinal grey matter before action potentials in intraspinal collaterals of afferent fibres reach their target neurons. Such modulation greatly depends on the actions of GABA via extrasynaptic membrane receptors. In the reported study we hypothesized that the increase in excitability of afferent fibres following epidural polarization close to the site where collaterals of afferent fibres leave the dorsal columns is due to the release of GABA from two sources: not only GABAergic interneurons but also glial cells. We present evidence, primo, that GABA released from both these sources contributes to a long-lasting increase in the excitability and a shortening of the refractory period of epidurally stimulated afferent fibres and, secondo, that effects of epidural polarization on the release of GABA are more critical for these changes than direct effects of DC on the stimulated fibres. The experiments were carried out in deeply anaesthetized rats in which changes in compound action potentials evoked in hindlimb peripheral nerves by dorsal column stimulation were used as a measure of the excitability of afferent fibres. The study throws new light on the modulation of input to spinal networks but also on mechanisms underlying the restoration of spinal functions.

Signalling of the neuropeptide calcitonin gene-related peptide (CGRP) through RAMP1 promotes liver fibrosis via TGFβ1/Smad2 and YAP pathways

The liver is innervated by primary sensory nerve fibres releasing the neuropeptide calcitonin gene-related peptide (CGRP). Elevated plasma levels of CGRP have been found in patients with liver fibrosis or cirrhosis. We hypothesised that signalling of CGRP and its receptors might regulate liver fibrosis and propose a novel potential target for the treatment. In this study, hepatic expression of CGRP and its receptor component, the receptor activity-modifying protein 1 (RAMP1), was dramatically increased in diseased livers of patients. In a murine liver fibrosis model, deficiency of RAMP1 resulted in attenuated fibrogenesis characterized by less collagen deposition and decreased activity of hepatic stellate cells (HSC). Mechanistically, activity of the TGFβ1 signalling core component Smad2 was severely impaired in the absence of RAMP1, and Yes-associated protein (YAP) activity was found to be diminished in RAMP1-deficient liver parenchyma. In vitro, stimulation of the HSC line LX-2 cells with CGRP induces TGFβ1 production and downstream signalling as well as HSC activation documented by increased α-SMA expression and collagen synthesis. We further demonstrate in LX-2 cells that CGRP promotes YAP activation and its nuclear translocation subsequent to TGFβ1/Smad2 signals. These data support a promotive effect of CGRP signalling in liver fibrosis via stimulation of TGFβ1/Smad2 and YAP activity.

The TRPA1 Ion Channel Mediates Oxidative Stress-Related Migraine Pathogenesis.

Although the introduction of drugs targeting calcitonin gene-related peptide (CGRP) revolutionized migraine treatment, still a substantial proportion of migraine patients do not respond satisfactorily to such a treatment, and new therapeutic targets are needed. Therefore, molecular studies on migraine pathogenesis are justified. Oxidative stress is implicated in migraine pathogenesis, as many migraine triggers are related to the production of reactive oxygen and nitrogen species (RONS). Migraine has been proposed as a superior mechanism of the brain to face oxidative stress resulting from energetic imbalance. However, the precise mechanism behind the link between migraine and oxidative stress is not known. Nociceptive primary afferent nerve fiber endings express ion channel receptors that change harmful stimuli into electric pain signals. Transient receptor potential cation channel subfamily A member 1 (TRPA1) is an ion channel that can be activated by oxidative stress products and stimulate the release of CGRP from nerve endings. It is a transmembrane protein with ankyrin repeats and conserved cysteines in its N-terminus embedded in the cytosol. TRPA1 may be a central element of the signaling pathway from oxidative stress and NO production to CGRP release, which may play a critical role in headache induction. In this narrative review, we present information on the role of oxidative stress in migraine pathogenesis and provide arguments that TRPA1 may be "a missing link" between oxidative stress and migraine and therefore a druggable target in this disease.

Effect of muscle length on the modulation of H-reflex and inhibitory mechanisms of Ia afferent discharges during passive muscle lengthening.

The effectiveness of activated Ia afferents to discharge α-motoneurons is decreased during passive muscle lengthening compared with static and shortening muscle conditions. Evidence suggests that these regulations are explained by 1) greater postactivation depression induced by homosynaptic postactivation depression (HPAD) and 2) primary afferent depolarization (PAD). It remains uncertain whether muscle length impacts the muscle lengthening-related aspect of regulation of the effectiveness of activated Ia afferents to discharge α-motoneurons, HPAD, PAD, and heteronymous Ia facilitation (HF). We conducted a study involving 15 healthy young individuals. We recorded conditioned or nonconditioned soleus Hoffmann (H) reflex with electromyography (EMG) to estimate the effectiveness of activated Ia afferents to discharge α-motoneurons, HPAD, PAD, and HF during passive shortening, static, and lengthening muscle conditions at short, intermediate, and long lengths. Our results show that the decrease of effectiveness of activated Ia afferents to discharge α-motoneurons and increase of postactivation depression during passive muscle lengthening occur at all muscle lengths. For PAD and HF, we found that longer muscle length increases the magnitude of regulation related to muscle lengthening. To conclude, our findings support an inhibitory effect (resulting from increased postactivation depression) of muscle lengthening and longer muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons. The increase in postactivation depression associated with muscle lengthening can be attributed to the amplification of Ia afferents discharge.NEW & NOTEWORTHY Original results are that in response to passive muscle lengthening and increased muscle length, inhibition of the effectiveness of activated Ia afferents to discharge α-motoneurons increases, with primary afferent depolarization and homosynaptic postactivation depression mechanisms playing central roles in this regulatory process. Our findings highlight for the first time a cumulative inhibitory effect of muscle lengthening and increased muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons.

ASPEK NEUROSAINS DALAM PATOFISIOLOGI PRURITUS NOKTURNAL

Itching at night in scabies patients is considered a very disturbing symptom. It is known that the main role of the itch sensation and subsequent motor response is to remove environmental influences from the skin, especially arthropods. The purpose of this article is to provide an understanding of the overall physiology and associated pathophysiology of itch. This article focuses on the neuronal aspect, as the nervous system is necessary to perceive the sensation of itch, as well as the multidirectional connections between the nervous and immune systems that influence the transmission of itch from the skin to the spinal cord. Itching is felt by skin nerve fibers called pruriceptors. These primary afferent fibers function as antennae and continuously sense the skin environment to detect and respond to cues. All major afferents project to the dorsal part of the spinal cord. Peptidergic and nonpeptidergic neurons target different areas of the dorsal superficial lamina. Based on this review, it can be concluded that noxious and pruritic stimuli are mostly processed in the superficial dorsal horn, whereas deeper dorsal horn neurons receive nociceptive and pruritic input via polysynaptic innervation.

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.

Mutual oligosynaptic inhibition of group Ia afferents between the anterior and posterior parts of the deltoid in humans.

The anterior (DA) and posterior parts of the deltoid (DP) show alternating contraction during shoulder flexion and extension movements. It is expected that an inhibitory spinal reflex between the DA and DP exists. In this study, spinal reflexes between the DA and DP were examined in healthy human subjects using post-stimulus time histogram (PSTH) and electromyogram averaging (EMG-A). Electrical conditioning stimulation was delivered to the axillary nerve branch that innervates the DA (DA nerve) and DP (DP nerve) with the intensity below the motor threshold. In the PSTH study, the stimulation to the DA and DP nerves inhibited (decrease in the firing probability) 31 of 54 DA motor units and 31 of 51 DP motor units. The inhibition was not provoked by cutaneous stimulation. The central synaptic delay of the inhibition between the DA and DP nerves was 1.5 ± 0.5ms and 1.4 ± 0.4ms (mean ± SD) longer than those of the homonymous facilitation of the DA and DP, respectively. In the EMG-A study, conditioning stimulation to the DA and DP nerves inhibited the rectified and averaged EMG of the DP and DA, respectively. The inhibition diminished with tonic vibration stimulation to the DA and DP and recovered 20-30min after vibration removal. These findings suggest that oligo(di or tri)-synaptic inhibition mediated by group Ia afferents between the DA and DP exists in humans.

Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most common off-target adverse effects caused by various chemotherapeutic agents, such as cisplatin, oxaliplatin, paclitaxel, vincristine and bortezomib. CIPN is characterized by a substantial loss of primary afferent sensory axonal fibers leading to sensory disturbances in patients. An estimated of 19-85% of patients developed CIPN during the course of chemotherapy. The lack of preventive measures and limited treatment options often require a dose reduction or even early termination of life-saving chemotherapy, impacting treatment efficacy and patient survival. In this Review, we summarized the current understanding on the pathogenesis of CIPN. One prominent change induced by chemotherapeutic agents involves the disruption of neuronal cytoskeletal architecture and axonal transport dynamics largely influenced by the interference of microtubule stability in peripheral neurons. Due to an ineffective blood-nerve barrier in our peripheral nervous system, exposure to some chemotherapeutic agents causes mitochondrial swelling in peripheral nerves, which lead to the opening of mitochondrial permeability transition pore and cytochrome c release resulting in degeneration of primary afferent sensory fibers. The exacerbated nociceptive signaling and pain transmission in CIPN patients is often linked the increased neuronal excitability largely due to the elevated expression of various ion channels in the dorsal root ganglion neurons. Another important contributing factor of CIPN is the neuroinflammation caused by an increased infiltration of immune cells and production of inflammatory cytokines. In the central nervous system, chemotherapeutic agents also induce neuronal hyperexcitability in the spinal dorsal horn and anterior cingulate cortex leading to the development of central sensitization that causes CIPN. Emerging evidence suggests that the change in the composition and diversity of gut microbiota (dysbiosis) could have direct impact on the development and progression of CIPN. Collectively, all these aspects contribute to the pathogenesis of CIPN. Recent advances in RNA-sequencing offer solid platform for in silico drug screening which enable the identification of novel therapeutic agents or repurpose existing drugs to alleviate CIPN, holding immense promises for enhancing the quality of life for cancer patients who undergo chemotherapy and improve their overall treatment outcomes.

Hypothalamic Paraventricular Stimulation Inhibits Nociceptive Wide Dynamic Range Trigeminocervical Complex Cells via Oxytocinergic Transmission.

Oxytocinergic transmission blocks nociception at the peripheral, spinal, and supraspinal levels through the oxytocin receptor (OTR). Indeed, a neuronal pathway from the hypothalamic paraventricular nucleus (PVN) to the spinal cord and trigeminal nucleus caudalis (Sp5c) has been described. Hence, although the trigeminocervical complex (TCC), an anatomical area spanning the Sp5c, C1, and C2 regions, plays a role in some pain disorders associated with craniofacial structures (e.g., migraine), the role of oxytocinergic transmission in modulating nociception at this level has been poorly explored. Hence, in vivo electrophysiological recordings of TCC wide dynamic range (WDR) cells sensitive to stimulation of the periorbital or meningeal region were performed in male Wistar rats. PVN electrical stimulation diminished the neuronal firing evoked by periorbital or meningeal electrical stimulation; this inhibition was reversed by OTR antagonists administered locally. Accordingly, neuronal projections (using Fluoro-Ruby) from the PVN to the WDR cells filled with Neurobiotin were observed. Moreover, colocalization between OTR and calcitonin gene-related peptide (CGRP) or OTR and GABA was found near Neurobiotin-filled WDR cells. Retrograde neuronal tracers deposited at the meningeal (True-Blue, TB) and infraorbital nerves (Fluoro-Gold, FG) showed that at the trigeminal ganglion (TG), some cells were immunopositive to both fluorophores, suggesting that some TG cells send projections via the V1 and V2 trigeminal branches. Together, these data may imply that endogenous oxytocinergic transmission inhibits the nociceptive activity of second-order neurons via OTR activation in CGRPergic (primary afferent fibers) and GABAergic cells.

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.

Effects of pulse width and frequency on evoked responses in electrostimulation: comparison between three muscle groups

Effects of pulse width and frequency on evoked responses in electrostimulation: comparison between three muscle groups

Whole Body Vibration's Potential to Improve Balance and Function in Cerebral Palsy in Weight and Non-Weight Bearing Positions: A Hypothesis Study

Cerebral palsy is one of the most prevalent neurological conditions in children. It has classical features of spasticity, poor balance and coordination, muscle weakness, proprioception, and inter-limb coordination. The primary cause is brain damage which affects certain circuits of the central nervous system. It has been reported that D1 inhibition is affected by cerebral palsy. The corticospinal and somatosensory pathways are also affected in the central nervous system along with abnormal activation of the motor neuron pool. There is abnormal presynaptic inhibition and post-activation depression of Ia afferents, while Group II facilitation is strongly enhanced. There are various therapies available to treat the symptoms of cerebral palsy, among which whole-body vibration therapy is considered to change the spinal transmission and somatosensory input. WBVT is typically administered in a weight bearing stance, targeting the lower extremities only. To the best of our knowledge, there is no research available exploring the cross-training effect of WBVT applied to upper and lower extremities, both weight and non-weight bearing positions, either alone on altogether. Hence, we propose that administering the WBVT across various configurations, incorporating weight and non-weight bearing positions for both upper and lower extremities could induce neural plasticity through cross training effect. We expect that by engaging all extremities in weight bearing positions may yield more significant outcomes compared to focusing solely on either upper or lower extremities.

Segmental motor neuron dysfunction in amyotrophic lateral sclerosis: Insights from H reflex paradigms.

In amyotrophic lateral sclerosis (ALS), the role of spinal interneurons in ALS is underrecognized. We aimed to investigate pre- and post-synaptic modulation of spinal motor neuron excitability by studying the H reflex, to understand spinal interneuron function in ALS. We evaluated the soleus H reflex, and three different modulation paradigms, to study segmental spinal inhibitory mechanisms. Homonymous recurrent inhibition (H'RI ) was assessed using the paired H reflex technique. Presynaptic inhibition of Ia afferents (H'Pre ) was evaluated using D1 inhibition after stimulation of the common peroneal nerve. We also studied inhibition of the H reflex after cutaneous stimulation of the sural nerve (H'Pos ). Fifteen ALS patients (median age 57.0 years), with minimal signs of lower motor neuron involvement and good functional status, and a control group of 10 healthy people (median age 57.0 years) were studied. ALS patients showed reduced inhibition, compared to controls, in all paradigms (H'RI 0.35 vs. 0.11, p = .036; H'Pre 1.0 vs. 5.0, p = .001; H'Pos 0.0 vs. 2.5, p = .031). The clinical UMN score was a significant predictor of the amount of recurrent and presynaptic inhibition. Spinal inhibitory mechanisms are impaired in ALS. We argue that hyperreflexia could be associated with dysfunction of spinal inhibitory interneurons. In this case, an interneuronopathy could be deemed a major feature of ALS.

Substance P Level in Patients with Degenerative Lumbar Spine Disorder undergoing Decompressive Surgery: An Observational Study

Introduction: Patients with degenerative lumbar spine disorders experience Chronic Low Back Pain (CLBP) for which they undergo decompressive surgery. Substance P (SP), a neurotransmitter which acts as a modulator of pain perception and transmits nociceptive signals via primary afferent fibers to the spinal cord and brainstem. In chronic painful conditions, SP level can be associated with the severity of pain and gets altered; however, this correlation is not present in acute pain. Aim: To evaluate serum SP level in CLBP patients undergoing decompressive spine surgery. Materials and Methods: The present study was a prospective observational study, in which 30 patients with CLBP undergoing decompressive spine surgery were enrolled. Along with them, one first-degree relative of each patient and an equal number of healthy volunteers were included in the study group. Patients were followed-up on the 5th postoperative day and at two months after surgery for the evaluation of SP levels and Visual Analogue Scale (VAS) scores. Statistical data analysis was carried out using IBM PASW Statistics (SPSS) 25.0 version software. SP levels followed a non normal distribution and were compared by Mann-Whitney U or Kruskal Wallis test (for 2 or more groups, respectively) and correlated using Spearman rank correlation. Results: Patients undergoing decompressive spine surgery had a significantly higher SP level (97.5 picogram/mL (pg/mL)) than healthy volunteers (23.22 pg/mL), p-value <0.001. The serum SP levels in patients were found to be significantly reduced on the 5th postoperative day (31.7 pg/mL) and at two months after surgery (48.5 pg/mL), p-value=0.043. In contrast, there was no discernible change in the VAS score, which did not correlate with the fall in SP levels on the 5th postoperative day. Conclusion: SP level was elevated in subjects with degenerative lumbar spine disorders undergoing decompressive surgery. Higher levels of SP can be attributed to CLBP in those patients. SP can be contemplated as a biomarker of pain due to degenerative lumbar spine pathology. However, further studies are warranted to substantiate this.

Tactile stimulation restores inhibited stretch reflex attributable to attenuation of Ia afferents during surprise landing

AbstractArthrogenic muscle inhibition (AMI) is induced by pathological knee conditions. The present study aimed to investigate the effect of tactile stimulation on reflex changes induced by simulated AMI during unpredictable landing performances. Twenty participants performed six unilateral landing tasks: 15 cm normal landing (15NL), 30 cm normal landing (30NL), surprise landing (SL), 30 cm normal landing following vibration (30NLV), SL following vibration (SLV), and SL following vibration with Kinesiology tape (SLK). For SL, the solid landing platform (15 cm) was removed and replaced by a false floor. Since the false floor dislodged easily under load, participants unpredictably fell through the platform to the actual landing surface 15 cm below. After completing 15NL, 30NL, and SL, vibration was applied to participants' knees to induce neurological changes similar to AMI. After vibration, participants performed 30NLV, SLV, and SLK in a random order. EMG signals in the post‐landing short latency (31–60 ms) and medium latency (61–90 ms) periods were examined. EMG signals from the vastus lateralis (VL), vastus medialis (VM), and biceps femoris (BF) were recorded and compared between tasks. EMG signals of all muscles in SL were significantly enhanced in the medium latency period as compared with 30NL. Enhanced EMG signals in SL were suppressed by vibration stimulation in the VL, but the suppressed EMG signals were restored after cutaneous stimulation with Kinesiology tape (p < 0.01). Our findings suggest that AMI could alter motor control patterns during unpredictable landing and that tactile stimulation could restore the altered motor control to a normal state.

Postsynaptic dorsal column pathway activation during spinal cord stimulation in patients with chronic pain.

Spinal cord stimulation (SCS) treatment for chronic pain relies on the activation of primary sensory fibres ascending to the brain in the dorsal columns. While the efficacy of SCS has been demonstrated, the precise mechanism of action and nature of the fibres activated by stimulation remain largely unexplored. Our investigation in humans with chronic neuropathic pain undergoing SCS therapy, found that post-synaptic dorsal column (PSDC) fibres can be activated synaptically by the primary afferents recruited by stimulation, and axonically by the stimulation pulses directly. Synaptic activation occurred in 9 of the 14 patients analysed and depended on the vertebral level of stimulation. A clear difference in conduction velocities between the primary afferents and the PSDC fibres were observed. Identification of PSDC fibre activation in humans emphasises the need for further investigation into the role they play in pain relief and the sensory response sensation (paraesthesia) experienced by patients undergoing SCS.

Sprouting of afferent and efferent inputs to pelvic organs after spinal cord injury.

Neural plasticity occurs within the central and peripheral nervous systems after spinal cord injury (SCI). Although central alterations have extensively been studied, it is largely unknown whether afferent and efferent fibers in pelvic viscera undergo similar morphological changes. Using a rat spinal cord transection model, we conducted immunohistochemistry to investigate afferent and efferent innervations to the kidney, colon, and bladder. Approximately 3-4 weeks after injury, immunostaining demonstrated that tyrosine hydroxylase (TH)-labeled postganglionic sympathetic fibers and calcitonin gene-related peptide (CGRP)-immunoreactive sensory terminals sprout in the renal pelvis and colon. Morphologically, sprouted afferent or efferent projections showed a disorganized structure. In the bladder, however, denser CGRP-positive primary sensory fibers emerged in rats with SCI, whereas TH-positive sympathetic efferent fibers did not change. Numerous CGRP-positive afferents were observed in the muscle layer and the lamina propria of the bladder following SCI. TH-positive efferent inputs displayed hypertrophy with large diameters, but their innervation patterns were sustained. Collectively, afferent or efferent inputs sprout widely in the pelvic organs after SCI, which may be one of the morphological bases underlying functional adaptation or maladaptation.

PAR2-dependent phosphorylation of TRPV4 at the trigeminal nerve terminals contributes to tongue cancer pain

ObjectiveThis study aimed to clarify the interactions between the tongue and primary afferent fibers in tongue cancer pain. MethodsA pharmacological analysis was conducted to evaluate mechanical hypersensitivity of the tongues of rats with squamous cell carcinoma (SCC). Changes in trigeminal ganglion (TG) neurons projecting to the tongue were analyzed using immunohistochemistry and western blotting. ResultsSCC inoculation of the tongue caused persistent mechanical sensitization and tumor formation. Trypsin expression was significantly upregulated in cancer lesions. Continuous trypsin inhibition or protease-activated receptor 2 (PAR2) antagonism in the tongue significantly inhibited SCC-induced mechanical sensitization. No changes were observed in PAR2 and transient receptor potential vanilloid 4 (TRPV4) levels in the TG or the number of PAR2-and TRPV4-expressing TG neurons after SCC inoculation. In contrast, the relative amount of phosphorylated TRPV4 in the TG was significantly increased after SCC inoculation and abrogated by PAR2 antagonism in the tongue. TRPV4 antagonism in the tongue significantly ameliorated the mechanical sensitization caused by SCC inoculation. ConclusionsOur findings indicate that tumor-derived trypsin sensitizes primary afferent fibers by PAR2 stimulation and subsequent TRPV4 phosphorylation, resulting in severe tongue pain.