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Frontiers in Physiology 2024Scientific evidence regarding the effect of different ladder-based resistance training (LRT) protocols on the morphology of the neuromuscular system is scarce....
Ladder-based resistance training with the progression of training load altered the tibial nerve ultrastructure and muscle fiber area without altering the morphology of the postsynaptic compartment.
Scientific evidence regarding the effect of different ladder-based resistance training (LRT) protocols on the morphology of the neuromuscular system is scarce. Therefore, the present study aimed to compare the morphological response induced by different LRT protocols in the ultrastructure of the tibial nerve and morphology of the motor endplate and muscle fibers of the soleus and plantaris muscles of young adult Wistar rats. Rats were divided into groups: sedentary control (control, n = 9), a predetermined number of climbs and progressive submaximal intensity (fixed, n = 9), high-intensity and high-volume pyramidal system with a predetermined number of climbs (Pyramid, n = 9) and lrt with a high-intensity pyramidal system to exhaustion (failure, n = 9). myelinated fibers and myelin sheath thickness were statistically larger in pyramid, fixed, and failure. myelinated axons were statistically larger in pyramid than in control. schwann cell nuclei were statistically larger in pyramid, fixed, and failure. microtubules and neurofilaments were greater in pyramid than in control. morphological analysis of the postsynaptic component of the plantar and soleus muscles did not indicate any significant difference. for plantaris, the type i myofibers were statistically larger in the pyramid and fixed compared to control. the pyramid, fixed, and failure groups for type ii myofibers had larger csa than control. for soleus, the type i myofibers were statistically larger in the pyramid than in control. pyramid and fixed had larger csa for type ii myofibers than control and failure. the pyramid and fixed groups showed greater mass progression delta than the failure. We concluded that the LRT protocols with greater volume and progression of accumulated mass elicit more significant changes in the ultrastructure of the tibial nerve and muscle hypertrophy without endplate changes.
PubMed: 38694209
DOI: 10.3389/fphys.2024.1371839 -
Frontiers in Neuroscience 2024Peripheral sensory neurons serve as the initial responders to the external environment. How these neurons react to different sensory stimuli, such as mechanical or...
INTRODUCTION
Peripheral sensory neurons serve as the initial responders to the external environment. How these neurons react to different sensory stimuli, such as mechanical or thermal forces applied to the skin, remains unclear.
METHODS
Using two-photon Ca imaging in the lumbar 4 dorsal root ganglion (DRG) of awake -GCaMP6s mice, we assessed neuronal responses to various mechanical (punctate or dynamic) and thermal forces (heat or cold) sequentially applied to the paw plantar surface.
RESULTS
Our data indicate that in normal awake male mice, approximately 14 and 38% of DRG neurons respond to either single or multiple modalities of stimulation. Anesthesia substantially reduces the number of responsive neurons but does not alter the ratio of cells exhibiting single-modal responses versus multi-modal responses. Following peripheral nerve injury, DRG cells exhibit a more than 5.1-fold increase in spontaneous neuronal activity and a 1.5-fold increase in sensory stimulus-evoked activity. As neuropathic pain resulting from nerve injury progresses, the polymodal nature of sensory neurons intensifies. The polymodal population increases from 39.1 to 56.9%, while the modality-specific population decreases from 14.7 to 5.0% within a period of 5 days.
DISCUSSION
Our study underscores polymodality as a significant characteristic of primary sensory neurons, which becomes more pronounced during the development of neuropathic pain.
PubMed: 38690372
DOI: 10.3389/fnins.2024.1368507 -
Rhode Island Medical Journal (2013) May 2024Children with Hunter syndrome have a high prevalence of nerve compression syndromes given the buildup of glycosaminoglycans in the tendon sheaths and soft tissue...
BACKGROUND
Children with Hunter syndrome have a high prevalence of nerve compression syndromes given the buildup of glycosaminoglycans in the tendon sheaths and soft tissue structures. These are often comorbid with orthopedic conditions given joint and tendon contractures due to the same pathology. While carpal tunnel syndrome and surgical treatment has been well-reported in this population, the literature on lower extremity nerve compression syndromes and their treatment in Hunter syndrome is sparse.
OBSERVATIONS
We report the case of a 13-year-old male with a history of Hunter syndrome who presented with toe-walking and tenderness over the peroneal and tarsal tunnel areas. He underwent bilateral common peroneal nerve and tarsal tunnel releases, with findings of severe nerve compression and hypertrophied soft tissue structures demonstrating fibromuscular scarring on pathology. Post-operatively, the patient's family reported subjective improvement in lower extremity mobility and plantar flexion.
LESSONS
In this case, peroneal and tarsal nerve compression were diagnosed clinically and treated effectively with surgical release and postoperative ankle casting. Given the wide differential of common comorbid orthopedic conditions in Hunter syndrome and the lack of validated electrodiagnostic normative values in this population, the history and physical examination and consideration of nerve compression syndromes are tantamount for successful workup and treatment of gait abnormalities in the child with Hunter syndrome.
Topics: Humans; Male; Adolescent; Mucopolysaccharidosis II; Tarsal Tunnel Syndrome; Peroneal Neuropathies; Peroneal Nerve; Nerve Compression Syndromes
PubMed: 38687262
DOI: No ID Found -
Military Medical Research Apr 2024The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain...
BACKGROUND
The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain incompletely understood.
METHODS
Wild-type (WT, n = 24), global Panx1 KO (n = 24), neuron-specific Panx1 KO (n = 20), and glia-specific Panx1 KO (n = 20) mice were used in this study at Albert Einstein College of Medicine. The von Frey test was used to quantify pain sensitivity in these mice following complete Freund's adjuvant (CFA) injection (7, 14, and 21 d). The qRT-PCR was employed to measure mRNA levels of Panx1, Panx2, Panx3, Cx43, Calhm1, and β-catenin. Laser scanning confocal microscopy imaging, Sholl analysis, and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons (DRGNs) in which Panx1 expression or function was manipulated. Ethidium bromide (EtBr) dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate (ATP) sensitivity. β-galactosidase (β-gal) staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia (TG) and DRG of transgenic mice.
RESULTS
Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli (7, 14, and 21 d; P < 0.01 vs. WT group), indicating that Panx1 was positively correlated with pain sensitivity. In Neuro2a, global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group (P < 0.05), revealing that Panx1 enhanced neurogenesis and excitability. Similarly, global Panx1 deletion significantly suppressed Wnt/β-catenin dependent DRG neurogenesis following 5 d of nerve growth factor (NGF) treatment (P < 0.01 vs. WT group). Moreover, Panx1 channels enhanced DRG neuron response to ATP after CFA injection (P < 0.01 vs. Panx1 KO group). Furthermore, ATP release increased Ca responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment (P < 0.01 vs. Panx1 KO group), suggesting that Panx1 in glia also impacts exaggerated neuronal excitability. Interestingly, neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs, as evidenced by stunted neurite outgrowth (P < 0.05 vs. Panx1 KO group; P < 0.01 vs. WT group or GFAP-Cre group), blunted activation of Wnt/β-catenin signaling (P < 0.01 vs. WT, Panx1 KO and GFAP-Cre groups), and diminished cell excitability (P < 0.01 vs. GFAP-Cre group) and response to ATP stimulation (P < 0.01 vs. WT group). Analysis of β-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher (2.5-fold increase) in the DRG than in the TG.
CONCLUSIONS
The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability. This hyperexcitability dependence on neuronal Panx1 contrasts with inflammatory orofacial pain, where similar studies revealed a prominent role for glial Panx1. The apparent differences in Panx1 expression in neuronal and non-neuronal TG and DRG cells are likely responsible for the distinct impact of these cell types in the two pain models.
Topics: Animals; Connexins; Mice; Nerve Tissue Proteins; Disease Models, Animal; Pain; Neurons; Inflammation; Mice, Knockout; Male
PubMed: 38685116
DOI: 10.1186/s40779-024-00525-8 -
Paediatrics and International Child... Apr 2024Nitrous oxide, an inhalational anaesthetic, is popular with adolescents worldwide as an accessible recreational drug which induces a euphoric effect. However, chronic...
Nitrous oxide, an inhalational anaesthetic, is popular with adolescents worldwide as an accessible recreational drug which induces a euphoric effect. However, chronic abuse leads to serious complications such as myeloneuropathy and bone marrow suppression by inactivation of vitamin B. A 17-year-old girl presented with nitrous oxide-induced myeloneuropathy. She reported chronic nitrous oxide inhalation for 10 months and was admitted to the emergency department on account of repeated falls for 2 weeks. She also had ascending paraesthesia in both legs and urinary incontinence. Neurological examination demonstrated bilateral lower extremity weakness [motor power: proximal muscles 4/5, plantar flexion and extensor hallucis longus (EHL) 3/5], decreased sensation, proprioception and vibration of the lower extremities. Deep tendon reflexes were absent in the ankles and knees. Laboratory results demonstrated mild anaemia [Hb 11.2 g/dL (12.0-16.0), haematocrit 35.4% (36-50), MCV 89.4 fl (78-102)] with significant hypersegmented neutrophils in a peripheral blood smear. Serum vitamin B was 340 pg/mL (197-771), but serum homocysteine was increased at 65.8 µmol/L (5-15). A nerve conduction study was prolonged, and F-waves were absent from the bilateral perineal and tibial nerves, indicating diffuse demyelinating motor polyneuropathy. Magnetic resonance imaging of the whole spine demonstrated faint T2 hypersignal intensity and an inverted V-shape appearance at the posterior column of the upper thoracic cord (around T2-T6), a pathognomonic sign of vitamin B deficiency or subacute combined degeneration of the nitrous oxide-induced myeloneuropathy. A 7-day course of 1000 µg cyanocobalamin was given intramuscularly, followed by weekly doses for 4 weeks. Supplements of daily oral vitamin B, B and B (65 µg vitamin B) were administered, along with rehabilitation. At the 6-months outpatient follow-up, there were a few residual neurological abnormalities: weakness of the left EHL (grade 4/5) and an absent deep tendon reflex in the left ankle. This case emphasises the significant health consequences of chronic abuse of nitrous oxide, myeloneuropathy and megaloblastic anaemia, by inactivation of vitamin B. The myelopathy is noticeably improved by cyanocobalamin. EHL: extensor hallucis longus; MRI: magnetic resonance imaging; NCS: nerve conduction study.
PubMed: 38682882
DOI: 10.1080/20469047.2024.2344403 -
Medicina (Kaunas, Lithuania) Mar 2024This study aims to identify the precise anatomical location and therapeutic mechanisms of the KI1 acupoint (Yongquan) in relation to foot muscles and nerves, known for...
This study aims to identify the precise anatomical location and therapeutic mechanisms of the KI1 acupoint (Yongquan) in relation to foot muscles and nerves, known for treating neurological disorders and pain. Dissection of six cadavers at Chungnam National University College of Medicine examined KI1's relation to the foot's four-layer structure. The KI1 acupoint was located in the superficial and deep layers of the plantar foot, adjacent to significant nerves like the medial and lateral plantar nerves. Differences in the acupoint's exact location between genders were noted, reflecting variances in foot morphology. KI1 acupuncture was found to stimulate the muscle spindles and nerve fibers essential for balance and bipedal locomotion. This stimulation may enhance sensory feedback, potentially improving cognitive functions and balance control. This anatomical insight into KI1 acupuncture underpins its potential in neurological therapies and pain management.
Topics: Humans; Acupuncture Points; Male; Female; Foot; Cadaver; Acupuncture Therapy; Tibial Nerve; Aged
PubMed: 38674181
DOI: 10.3390/medicina60040535 -
Brain Research Bulletin Jun 2024Intraoperative remifentanil administration has been linked to increased postoperative pain sensitivity. Recent studies have identified the involvement of euchromatic...
Euchromatin histone-lysine N-methyltransferase 2 regulates the expression of potassium-sodium-activated channel subfamily T member 1 in primary sensory neurons and contributes to remifentanil-induced pain sensitivity.
Intraoperative remifentanil administration has been linked to increased postoperative pain sensitivity. Recent studies have identified the involvement of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2/G9a) in neuropathic pain associated with the transcriptional silencing of many potassium ion channel genes. This study investigates whether G9a regulates the potassium sodium-activated channel subfamily T member 1 (Slo2.2) in remifentanil-induced post-incisional hyperalgesia (RIH) in rodents. We performed remifentanil infusion (1 μg·kg-1·min-1 for 60 min) followed by plantar incision to induce RIH in rodents. Our results showed that RIH was accompanied by increased G9a and H3K9me2 production and decreased Slo2.2 expression 48 h postoperatively. Deletion of G9a rescued Slo2.2 expression in DRG and reduced RIH intensity. Slo2.2 overexpression also reversed this hyperalgesia phenotype. G9a overexpression decreased Slo2.2-mediated leak current and increased excitability in the small-diameter DRG neurons and laminal II small-diameter neurons in the spinal dorsal horn, which was implicated in peripheral and central sensitization. These results suggest that G9a contributes to the development of RIH by epigenetically silencing Slo2.2 in DRG neurons, leading to decreased central sensitization in the spinal cord. The findings may have implications for the development of novel therapeutic targets for the treatment of postoperative pain.
Topics: Animals; Histone-Lysine N-Methyltransferase; Male; Remifentanil; Hyperalgesia; Sensory Receptor Cells; Potassium Channels, Sodium-Activated; Mice; Analgesics, Opioid; Ganglia, Spinal; Neuralgia; Pain, Postoperative; Rats; Pain Threshold; Rats, Sprague-Dawley; Mice, Inbred C57BL; Nerve Tissue Proteins
PubMed: 38670469
DOI: 10.1016/j.brainresbull.2024.110966 -
International Journal of Exercise... 2024The main objective was to ascertain the acute responses in autonomic nervous activity and peripheral sensation induced by moderate-intensity treadmill exercise performed...
OBJECTIVE
The main objective was to ascertain the acute responses in autonomic nervous activity and peripheral sensation induced by moderate-intensity treadmill exercise performed under different ambient temperatures.
METHODS
Twelve young healthy subjects underwent three sessions of moderate-intensity treadmill exercise (warming, 5 min and running, 25 min), on different days under 10°C, 20°C and 30°C room temperatures. Pre- and post-intervention, heart rate variability (HRV) and plantar vibrotactile perception threshold (VPT) were measured. Additionally, rate of perceived exertion (RPE) was recorded after intervention.
RESULTS
In comparison with the corresponding baseline values, after intervention, low frequency power (LF) and LF/high frequency power (HF) of HRV increased significantly and HF decreased significantly under the condition of 10°C only ( < .005). Following intervention, VPT increased significantly at the hallux for 31.5 Hz test frequency under 30°C and at the heel for 31.5 Hz test frequency under 10°C (both < .05). In contrast, VPT decreased significantly at the hallux for 125 Hz test frequency under 10°C ( < .005). Exposure under the temperature of 20°C did not result in any significant change in VPT. After intervention, RPE under 30°C showed significantly higher values than those under 20°C ( < .01) and 10°C ( < .005) conditions with no difference between the latter two conditions.
CONCLUSIONS
Treadmill exercise under 20°C ambient temperature did not exert any negative impacts on autonomic and peripheral nerve function and resulted in a perceived exertion of moderate intensity among the study participants. Therefore, an ambient temperature around 20°C might be recommended for the mentioned purpose.
PubMed: 38665327
DOI: No ID Found -
Pain Medicine (Malden, Mass.) Apr 2024Ultrasound-guided tibial nerve pulsed radiofrequency (US-TN PRF) and fluoroscopy-guided intralesional radiofrequency thermocoagulation (FL-RFT) adjacent to the painful...
Comparison of tibial nerve pulsed radiofrequency and intralesional radiofrequency thermocoagulation in the treatment of painful calcaneal spur and plantar fasciitis: A randomized clinical trial.
OBJECTIVE
Ultrasound-guided tibial nerve pulsed radiofrequency (US-TN PRF) and fluoroscopy-guided intralesional radiofrequency thermocoagulation (FL-RFT) adjacent to the painful calcaneal spur are two interventions for pain management in painful calcaneal spur (PCS) and plantar fasciitis (PF). This study aimed to compare the effectiveness of the two procedures.
DESIGN
A prospective, randomized, single-blind study.
SETTING
Single-center pain clinic.
SUBJECTS
Forty-nine patients who met the inclusion criteria were randomized into two groups.
METHODS
25 patients (group U) received US-TN PRF at 42 °C for 240 s, while 24 patients (group F) received intralesional FL-RFT at 80 °C for 90 s. The most severe Numeric Rating Scale (NRS) score during the first morning steps and the American Orthopedic Foot and Ankle Society (AOFAS) ankle hindfoot scores were used to evaluate the effectiveness of the procedures. The study's primary outcome assessed treatment effectiveness using the NRS, whereas the secondary outcomes included changes in the AOFAS score and the incidence of procedure-related mild adverse events.
RESULTS
NRS and AOFAS scores significantly improved in groups U and F at 1 and 3 months compared to baseline (p < 0.05), and there was no significant difference between the groups. At month 1, 50% or greater pain relief was achieved in 72% of patients in group U and 75% in group F. No significant difference was observed in the incidence of mild adverse events between the groups.
CONCLUSIONS
US-TN PRF and intralesional FL-RFT have shown significant effectiveness in the treatment of PCS and PF. Larger randomized controlled trials are needed.
PubMed: 38652568
DOI: 10.1093/pm/pnae029 -
Science Translational Medicine Apr 2024Spontaneous pain, a major complaint of patients with neuropathic pain, has eluded study because there is no reliable marker in either preclinical models or clinical...
Spontaneous pain, a major complaint of patients with neuropathic pain, has eluded study because there is no reliable marker in either preclinical models or clinical studies. Here, we performed a comprehensive electroencephalogram/electromyogram analysis of sleep in several mouse models of chronic pain: neuropathic (spared nerve injury and chronic constriction injury), inflammatory (Freund's complete adjuvant and carrageenan, plantar incision) and chemical pain (capsaicin). We find that peripheral axonal injury drives fragmentation of sleep by increasing brief arousals from non-rapid eye movement sleep (NREMS) without changing total sleep amount. In contrast to neuropathic pain, inflammatory or chemical pain did not increase brief arousals. NREMS fragmentation was reduced by the analgesics gabapentin and carbamazepine, and it resolved when pain sensitivity returned to normal in a transient neuropathic pain model (sciatic nerve crush). Genetic silencing of peripheral sensory neurons or ablation of CGRP neurons in the parabrachial nucleus prevented sleep fragmentation, whereas pharmacological blockade of skin sensory fibers was ineffective, indicating that the neural activity driving the arousals originates ectopically in primary nociceptor neurons and is relayed through the lateral parabrachial nucleus. These findings identify NREMS fragmentation by brief arousals as an effective proxy to measure spontaneous neuropathic pain in mice.
Topics: Humans; Rats; Mice; Animals; Nociceptors; Eye Movements; Hyperalgesia; Rats, Sprague-Dawley; Neuralgia; Sleep; Disease Models, Animal
PubMed: 38630850
DOI: 10.1126/scitranslmed.adg3036