Electric field stimulation (EFS) can effectively inhibit local Ca ²⁺ influx and secondary injury after spinal cord injury (SCI). However, after the EFS, the Ca ²⁺ in the injured spinal cord restarts and subsequent biochemical reactions are stimulated, which affect the long-term effect of EFS. Polyethylene glycol (PEG) is a hydrophilic polymer material that can promote cell membrane fusion and repair damaged cell membranes. This article aims to study the combined effects of EFS and PEG on the treatment of SCI. Sprague-Dawley (SD) rats were subjected to SCI and then divided into control group (no treatment, n = 10), EFS group (EFS for 30 min, n = 10), PEG group (covered with 50% PEG gelatin sponge for 5 min, n = 10) and combination group (combined treatment of EFS and PEG, n = 10). The measurement of motor evoked potential (MEP), the motor behavior score and spinal cord section fast blue staining were performed at different times after SCI. Eight weeks after the operation, the results showed that the latency difference of MEP, the amplitude difference of MEP and the ratio of cavity area of spinal cords in the combination group were significantly lower than those of the control group, EFS group and PEG group. The motor function score and the ratio of residual nerve tissue area in the spinal cords of the combination group were significantly higher than those in the control group, EFS group and PEG group. The results suggest that the combined treatment can reduce the pathological damage and promote the recovery of motor function in rats after SCI, and the therapeutic effects are significantly better than those of EFS and PEG alone.
Animals ; Electric Stimulation ; Polyethylene Glycols/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Recovery of Function/physiology* ; Spinal Cord ; Spinal Cord Injuries/therapy*

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.
Analgesics ; Animals ; Narcotic Antagonists/pharmacology* ; Neuralgia/therapy* ; Opioid Peptides ; Rats ; Receptors, Opioid/physiology* ; Receptors, Opioid, kappa ; Spinal Cord ; Spinal Cord Stimulation

Spinal cord stimulation (SCS) for pain is usually implanted as an open loop system using unchanged parameters. To avoid the under and over stimulation caused by lead migration, evoked compound action potentials (ECAP) is used as feedback signal to change the stimulating parameters. This study established a simulation model of ECAP recording to investigate the relationship between ECAP component and dorsal column (DC) fiber recruitment. Finite element model of SCS and multi-compartment model of sensory fiber were coupled to calculate the single fiber action potential (SFAP) caused by single fiber in different spinal cord regions. The synthetized ECAP, superimposition of SFAP, could be considered as an index of DC fiber excitation degree, because the position of crests and amplitude of ECAP corresponds to different fiber diameters. When 10% or less DC fibers were excited, the crests corresponded to fibers with large diameters. When 20% or more DC fibers were excited, ECAP showed a slow conduction crest, which corresponded to fibers with small diameters. The amplitude of this slow conduction crest increased as the stimulating intensity increased while the amplitude of the fast conduction crest almost remained unchanged. Therefore, the simulated ECAP signal in this paper could be used to evaluate the degree of excitation of DC fibers. This SCS-ECAP model may provide theoretical basis for future clinical application of close loop SCS base on ECAP.
Action Potentials ; Computer Simulation ; Electric Stimulation ; Evoked Potentials ; Spinal Cord ; Spinal Cord Stimulation

OBJECTIVE: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on neurological and functional recovery in patients with central cord syndrome (CCS) involving the upper extremities between the treated and non-treated sides of the treated group and whether the outcomes are comparable to that of the untreated control group. METHODS: Nineteen CCS patients were treated with high-frequency (20 Hz) rTMS over the motor cortex for 5 days. The stimulation side was randomly selected, and all the subjects received conventional occupational therapy during the rTMS-treatment period. Twenty CCS patients who did not receive rTMS were considered as controls. Clinical assessments, including those by the International Standard for Neurological Classification of Spinal Cord Injury, the Jebsen-Taylor Hand Function Test, and the O'Connor Finger Dexterity Test were performed initially and followed up for 1 month after rTMS treatment or 5 weeks after initial assessments. RESULTS: The motor scores for upper extremities were increased and the number of improved cases was greater for the treated side in rTMS-treated patients than for the non-treated side in rTMS-treated patients or controls. The improved cases for writing time and score measured on the Jebsen-Taylor Hand Function Test were also significantly greater in number on the rTMS-treated side compared with the non-treated side and controls. There were no adverse effects during rTMS therapy or the follow-up period. CONCLUSION: The results of the application of high-frequency rTMS treatment to CCS patients suggest that rTMS can enhance the motor recovery and functional fine motor task performance of the upper extremities in such individuals.
Central Cord Syndrome ; Classification ; Fingers ; Follow-Up Studies ; Hand ; Humans ; Motor Cortex ; Occupational Therapy ; Spinal Cord Injuries ; Task Performance and Analysis ; Transcranial Magnetic Stimulation ; Upper Extremity ; Writing

BACKGROUND: It is uncommon for patients who have received a permanent implant to remove the spinal cord stimulator (SCS) after discontinuation of medication in complex regional pain syndrome (CRPS) due to their completely painless state. This study evaluated CRPS patients who successfully removed their SCSs. METHODS: This 10-year retrospective study was performed on patients who had received the permanent implantation of an SCS and had removed it 6 months after discontinuation of stimulation, while halting all medications for neuropathic pain. Age, sex, duration of implantation, site and type of CRPS, and their return to work were compared between the removal and non-removal groups. RESULTS: Five (12.5%, M/F = 4/1) of 40 patients (M/F = 33/7) successfully removed the permanent implant. The mean age was younger in the removal group (27.2 ± 6.4 vs. 43.5 ± 10.7 years, P < 0.01). The mean duration of implantation in the removal group was 34.4 ± 18.2 months. Two of 15 patients (13.3%) and 3 of 25 patients (12%) who had upper and lower extremity pain, respectively, had removed the implant. The implants could be removed in 5 of 27 patients (18.5%) with CRPS type 1 (P < 0.01). All 5 patients (100%) who removed their SCS returned to work, while only 5 of 35 (14.3%) in the non-removal group did (P < 0.01). CONCLUSIONS: Even though this study had limited data, younger patients with CRPS type 1 could remove their SCSs within a 5-year period and return to work with complete pain relief.
Age Factors ; Device Removal ; Extremities ; Humans ; Lower Extremity ; Neuralgia ; Retrospective Studies ; Return to Work ; Spinal Cord Stimulation ; Spinal Cord

PURPOSE: To determine if self-administered transcutaneous tibial nerve stimulation (TTNS) is a feasible treatment option for neurogenic bladder among people with spinal cord injury (SCI) who utilize intermittent catheterization for bladder management. METHODS: Four-week observational trial in chronic SCI subjects performing intermittent catheterization with incontinence episodes using TTNS at home daily for 30 minutes. Those using anticholinergic bladder medications were given a weaning schedule to begin at week 2. Primary outcomes were compliance and satisfaction. Secondary outcomes included change in bladder medications, efficacy based on bladder diary, adverse events, and incontinence quality of life (I-QoL) survey.
Appointments and Schedules ; Catheterization ; Catheters ; Compliance ; Humans ; Mouth ; Quality of Life ; Sleep Stages ; Spinal Cord Injuries ; Spinal Cord ; Tibial Nerve ; Transcutaneous Electric Nerve Stimulation ; Urinary Bladder ; Urinary Bladder, Neurogenic ; Urodynamics ; Weaning

STUDY DESIGN: Animal study. OBJECTIVES: To investigate the effects of microelectric treatment by transcutaneous electrical nerve stimulation (TENS) on functional recovery and histological changes in a rat model of spinal cord injury (SCI). SUMMARY OF LITERATURE REVIEW: The effects of TENS on spasticity and its underlying mechanisms remain unclear. MATERIALS AND METHODS: SCI was induced by a 1.5-mm impactor with 200,000–260,000 dyne after laminectomy. Rats were divided into the following groups: group I (normal control), group II (microelectric treatment of 0 A), group III (microelectric treatment of 100 µA for 1 hr/day), group IV (microelectric treatment of 400 µA for 1 hr/day), and group V (microelectric treatment of 400 µA for 24 hr/day). After inducing SCI, rats were assessed by a sensory test with von Frey filaments and the locomotor recovery test (BBB rating scale) at 1, 4, 7, 14, 21, and 28 days. To evaluate spinal cord damage, histopathological studies were performed with hematoxylin and eosin. Brain-derived neurotrophic factor (BDNF) and TrkB immunohistochemistry studies were performed at 28 days. RESULTS: In groups IV and V, the BBB score had significantly improved on days 21 and 28 after SCI, and the TENS-treated groups showed significant neuronal recovery. After SCI, groups IV and V showed a significant recovery of locomotor function and the motor sensory response of the withdrawal threshold to 3.5 g. In addition, necrotic tissue and cystic spaces in the spinal cord were significantly reduced and BDNF/TrkB-positive cells were highly expressed in groups III, IV, and V. CONCLUSIONS: Microelectric treatment can play a role in facilitating the recovery of locomotion following SCI.
Animals ; Brain-Derived Neurotrophic Factor ; Eosine Yellowish-(YS) ; Hematoxylin ; Immunohistochemistry ; Laminectomy ; Locomotion ; Models, Animal ; Muscle Spasticity ; Neurons ; Rats ; Spinal Cord Injuries ; Spinal Cord ; Transcutaneous Electric Nerve Stimulation

The nineteenth century neuroscience studied the instinct of animal to understand the human mind. In particular, it has been found that the inheritance of unconscious behavior like instinct is mediated through ganglion chains, such as the spinal cord or sympathetic nervous system, which control unconscious reflexes. At the same time, the theory of Inheritance of Acquired Characteristics (hereafter ‘IAC’) widely known as Lamarck's evolutionary theory provided the theoretical frame on the origin of instinct and the heredity of action that the parental generation's habits were converted into the nature of the offspring generation. Contrary to conventional knowledge, this theory was not originally invented by Lamarck, and Darwin also did not discard this theory even after discovering the theory of natural selection in 1838 and maintained it throughout his intellectual life. Above all, in the field of epigenetics, the theory of ‘IAC’ has gained attention as a reliable scientific theory today. Darwin discovered crucial errors in the late 1830s that the Lamarck version's theory of ‘IAC’ did not adequately account for the principle of the inheritance of unconscious behavior like instinct. Lamarck's theory regarded habits as conscious and willful acts and saw that those habits are transmitted through the brain to control conscious actions. Lamarck's theory could not account for the complex and elaborate instincts of invertebrate animals, such as brainless ants. Contrary to Lamarck's view, Darwin established the new theory of ‘IAC’ that could be combined with contemporary neurological theory, which explains the heredity of unconscious behavior. Based on the knowledge of neurology, Darwin was able to translate the ‘principle of habit’ into a neurological term called ‘principle of reflex’. This article focuses on how Darwin join the theory of ‘IAC’ with nineteenth century neuroscience and how the neurological knowledge from the nineteenth century contributed to Darwin's overcoming of Lamarck's ‘IAC’. The significance of this study is to elucidate Darwin's notion of ‘IAC’ theory rather than natural selection theory as a principle of heredity of behavior. The theory of ‘IAC’ was able to account for the rapid variation of instincts in a relatively short period of time, unlike natural selection, which operates slowly in geological time spans of tens of millions of years. The nineteenth century neurological theory also provided neurological principles for ‘plasticity of instinct,’ empirically supporting the fact that all nervous systems responsible for reflexes respond sensitively to very fine stimuli. However, researchers of neo-Darwinian tendencies, such as Richard Dawkins and evolutionary psychologists advocating the ‘selfish gene’ hypothesis, which today claim to be Darwin's descendants, are characterized by human nature embedded in biological information, such as the brain and genes, so that it cannot change at all. This study aims to contribute to reconstructing the evolutionary discourse by illuminating Darwin's insights into the “plasticity of nature” that instincts can change relatively easily even at the level of invertebrates such as earthworms.
Animals ; Ants ; Brain ; Epigenomics ; Ganglion Cysts ; Heredity ; Human Characteristics ; Humans ; Instinct ; Invertebrates ; Nervous System ; Neurology ; Neurosciences ; Oligochaeta ; Parents ; Psychology ; Reflex ; Selection, Genetic ; Spinal Cord ; Sympathetic Nervous System ; Transcutaneous Electric Nerve Stimulation ; Wills

In addition to restoration of bladder, bowel, and motor functions, alleviating the accompanying debilitating pain is equally important for improving the quality of life of patients with spinal cord injury (SCI). Currently, however, the treatment of chronic pain after SCI remains a largely unmet need. Electrical spinal cord stimulation (SCS) has been used to manage a variety of chronic pain conditions that are refractory to pharmacotherapy. Yet, its efficacy, benefit profiles, and mechanisms of action in SCI pain remain elusive, due to limited research, methodological weaknesses in previous clinical studies, and a lack of mechanistic exploration of SCS for SCI pain control. We aim to review recent studies and outline the therapeutic potential of different SCS paradigms for traumatic SCI pain. We begin with an overview of its manifestations, classification, potential underlying etiology, and current challenges for its treatment. The clinical evidence for using SCS in SCI pain is then reviewed. Finally, future perspectives of pre-clinical research and clinical study of SCS for SCI pain treatment are discussed.
Animals ; Chronic Pain ; Humans ; Pain ; etiology ; Pain Management ; methods ; Quality of Life ; Spinal Cord Injuries ; complications ; Spinal Cord Stimulation ; Treatment Outcome

Peripheral arterial disease is one part of systematic atherosclerosis, becoming a heavy burden of human health. Patients in end stage of peripheral arterial disease manifest critical limb ischemia with severe rest pain and refractory ulcer. Surgical revascularization is the optimal option for patients with critical limb ischemia to avoid major amputation and improve quality of life. However, some of them contraindicate surgical revascularizations owing to coexisting morbidities. Spinal cord stimulation is reported to be effective and minimally invasive in pain relief and limb salvage for patients with limb ischemia. Here, we reported one case with chronic critical limb ischemia and gangrene of foot who underwent spinal cord stimulation, which was, as we knew, the first case in China. He was diagnosed with Burger disease and accompanied with history of stroke, chronic obstructive pulmonary disease and Castleman's disease. It showed totally occlusive lesions of external iliac and femoropopliteal artery and no outflows below the knee in the computed tomography angiography. Given the complexity of lesions and weakness of the patient, spinal cord stimulation was indicated for control of rest pain and limb salvage. As specified, we implanted the temporary neurostimulator as the first step. After 2 weeks from temporary neurostimulator implantation, the patient achieved significant relief in intensity of pain, and acquired 20% improvement of transcutaneous oxygen pressure. The satisfactory results indicated probable effectiveness of spinal cord stimulation, thus we performed the permanent neurostimulator implantation 1 month later. During 2 months of follow-up, the patients stabilized at Fountain III with pain relief with one kind of nonsteroidal anti-inflammatory drug. In our case, we confirmed the significant validity of spinal cord stimulation for pain control and consequent improvement of quality of life in non-reconstructable chronic critical limb ischemia. Furthermore, we reviewed that a number of published studies suggested that spinal cord stimulation be a reasonable option for patients with critical rest pain, especially who contraindicated surgical revascularization. The application of spinal cord stimulation in pain relief for non-reconstructable chronic critical limb ischemia was approved by related guidelines released by European Society of Cardiology and Trans-Atlantic Inter-Society Consensus. Further investigations are required for assessing the long-term outcome in limb salvage.
China ; Humans ; Ischemia ; Leg ; Limb Salvage ; Male ; Quality of Life ; Spinal Cord ; Spinal Cord Stimulation ; Treatment Outcome