Laser speckle contrast imaging to predict the effect of temporary spinal cord stimulation in postherpetic neuralgia patients: A prospective observational study

Temporary spinal cord stimulation(tSCS)can effectively reduce the pain and severity of postherpetic neuralgia(PHN).However,there are no effective and objective methods for predicting the effects of tSCS on PHN.Laser speckle contrast imaging(LSCI)is frequently used in neurology to evaluate the effectiveness of treatment.To assess the accuracy of LSCI in predicting the impact of tSCS on PHN,14 adult patients receiving tSCS treatments for spinal nerve-innervated(C6-T2)PHN participated in this observational study.Visual analog scale(VAS)assessments and LSCI bloodflow images of the-ngers were recorded after the tSCS procedure.The results showed that the VAS scores of all patients decreased signi-cantly.Moreover,the bloodflow index(BFI)values were signi-cantly higher than they were before the procedure.Increased bloodflow and pain alleviation were positively correlated.The-ndings indicated that spinal nerve PHN(C6-T2)was signi-cantly reduced by tSCS.Pain alleviation by tSCS was positively correlated with increased bloodflow in the hand.The effect of tSCS on PHN may thus be predicted using an independent and consistent indicator such as LSCI.

Effects of spinal cord stimulation on cerebrovascular flow: role of sym-pathetic and parasympathetic innervations

Objective Cervical spinal cord stimulation （SCS） has been found to augment cerebral blood flow （CBF） in a number of animal models. However, the effective use of SCS is hampered by a lack of understanding of its mechanism（s） of action. In this paper, we focus on the sympathetic and parasympathetic effects of SCS on CBF. Method SpragueDawley rats were selected for the experimental series. The animals were divided into 5 groups to underwent SCS and laser Doppler flowmeter （LDF） recordings. Control group, the animal underwent SCS and LDF recordings without any surgery of the nerve fibers and ganglia. V 1 group, the animal underwent bilateral resection of the nasociliary and post-ganglionic parasympathetic nerve fibbers. SCG group, the animal underwent bilateral resection of supper cervical ganglion. V 1 ＋ SCG group, the animal underwent both surgeries as V1- and SCG-group animals did. Sham group, the animal underwent the carotid manipulation with blunt-tipped forceps as well as the dissection of nasociliary and post-ganglionic parasympathetic nerve fibers around the ethmoidal foramen, but without cutting any nerves. Results During the SCS, the LDF was no statistical difference between the V 1 or SCG group and the control group. Yet, the effects of SCS on CBF are completely abolished in V1＋ SCG group. Conclusions Surgical interruption of both the parasympathetic and sympathetic pathways has the contradict effect on SCS-induced CBF augmentation.

High-frequency spinal cord stimulation produces longlasting analgesic effects by restoring lysosomal function and autophagic flux in the spinal dorsal horn

High-frequency spinal cord stimulation(HF-SCS) has been established as an effective therapy for neuropathic pain. However, the analgesic mechanisms involved in HF-SCS remain to be clarified. In our study, adult rat neuropathic pain was induced by spinal nerve ligation. Two days after modeling, the rats were subjected to 4 hours of HF-SCS(motor threshold 50%, frequency 10,000 Hz, and pulse width 0.024 ms) in the dorsal horn of the spinal cord. The results revealed that the tactile allodynia of spinal nerve-injured rats was markedly alleviated by HFSCS, and the effects were sustained for 3 hours after the stimulation had ceased. HF-SCS restored lysosomal function, increased the levels of lysosome-associated membrane protein 2(LAMP2) and the mature form of cathepsin D(matu-CTSD), and alleviated the abnormally elevated levels of microtubule-associated protein 1 A/B-light chain 3(LC3)-II and sequestosome 1(P62) in spinal nerve-injured rats. HF-SCS also mostly restored the immunoreactivity of LAMP2, which was localized in neurons in the superficial layers of the spinal dorsal horn in spinal nerve-injured rats. In addition, intraperitoneal administration of 15 mg/kg chloroquine for 60 minutes reversed the expression of the aforementioned proteins and shortened the timing of the analgesic effects of HF-SCS. These findings suggest that HF-SCS may exhibit longlasting analgesic effects on neuropathic pain in rats through improving lysosomal dysfunction and alleviating autophagic flux. This study was approved by the Laboratory Animal Ethics Committee of China Medical University, Shenyang, China(approval No. 2017 PS196 K) on March 1, 2017.

A flexible electrode array for determining regions of motor function activated by epidural spinal cord stimulation in rats with spinal cord injury

Epidural stimulation of the spinal cord is a promising technique for the recovery of motor function after spinal cord injury.The key challenges within the reconstruction of motor function for paralyzed limbs are the precise control of sites and parameters of stimulation.To activate lower-limb muscles precisely by epidural spinal cord stimulation,we proposed a high-density,flexible electrode array.We determined the regions of motor function that were activated upon epidural stimulation of the spinal cord in a rat model with complete spinal cord,which was established by a transection method.For evaluating the effect of stimulation,the evoked potentials were recorded from bilateral lowerlimb muscles,including the vastus lateralis,semitendinosus,tibialis anterior,and medial gastrocnemius.To determine the appropriate stimulation sites and parameters of the lower muscles,the stimulation characteristics were studied within the regions in which motor function was activated upon spinal cord stimulation.In the vastus lateralis and medial gastrocnemius,these regions were symmetrically located at the lateral site of L1 and the medial site of L2 vertebrae segment,respectively.The tibialis anterior and semitendinosus only responded to stimulation simultaneously with other muscles.The minimum and maximum stimulation threshold currents of the vastus lateralis were higher than those of the medial gastrocnemius.Our results demonstrate the ability to identify specific stimulation sites of lower muscles using a high-density and flexible array.They also provide a reference for selecting the appropriate conditions for implantable stimulation for animal models of spinal cord injury.This study was approved by the Animal Research Committee of Southeast University,China(approval No.20190720001) on July 20,2019.

Spinal Cord Stimulation for Refractary Neuropathic Pain and Its Action on the Neurovegetative Systems

BACKGROUND: Spinal Cord Stimulation (SCS) has been used for chronic refractory pain, however its effectivity on neurovegetative systems has not been evaluated to data. OBJECTIVES: The study was conducted to evaluate the effect of SCS in patients suffering from refractory neuropathic pain, related to analgesia, quality of life and neurovegetative actions on the digestive and urinary tracts. Fifteen patients acted as their own control related to all evaluations. P < 0.05 was considered significantly. RESULTS: 13 patients completed the study. The incidence of indication was 6% in our Center for Pain Treatment in the Teaching Hospital. The SCS improved quality of life, bowel transit and urinary function, as improved overall analgesia and decreased daily rescue analgesic (p < 0.001). CONCLUSIONS: In accordance with literature, the incidence of complications was 20%, and SCS improved analgesia and quality of life. In addition, patients also referred to improved bowel activity and urinary function.

Spinal Cord Stimulation (SCS) for Pain Control in a Quadriplegic Patient: A Case Report

Background: There are reports of pain relief from spinal cord stimulation (SCS) in patients with incomplete spinal cord injuries. However, the results for pain relief from SCS in patients with complete spinal cord injury are dismal. Patients with complete spinal cord injury therefore are generally not considered suitable candidates for SCS. The authors report a case in which a quadriplegic patient with cervical spinal cord injury got significant pain relief from spinal cord stimulation. Methods: The patient is 41 years old with quadriplegia secondary to C5-6 injury. He has no function below the level of the injury except for a few patchy areas of sensation. Ten years after the injury the patient had hemorrhoidectomy. This resulted in severe pain in the anal pain. The treatment for pain failed conservative treatment. He however did have good response to a trial of spinal cord stimulation through an epidural lead placed at T8-T9 vertebral body level. Permanent implantation of spinal cord stimulator was therefore performed. Results: At preoperative evaluation the patient rated his pain as a 7/10. Presently at 2 years’ follow-up the patient rates his pain at 1/10. Conclusions: Spinal cord stimulation proved to be a successful means of achieving adequate pain relief in a patient who had complete loss of motor function below the level of the injury. Therefore, although patients with such condition are unlike to benefit from SCS it is worthwhile trying this treatment if no other option is available there.

Spinal Cord Stimulation Enhances Microglial Activation in the Spinal Cord of Nerve-Injured Rats

Microglia can modulate spinal nociceptive transmission.Yet,their role in spinal cord stimulation(SCS)-induced pain inhibition is unclear.Here,we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury(CCI)of the sciatic nerve.Male rats received conventional SCS(50 Hz,80%motor threshold,180 min,2 sessions/day)or sham stimulation on days 18-20 post-CCI.SCS transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal horns.SCS also upregulated the mRNAs of Ml-like markers,but not M2-like markers.Inducible NOS protein expression was increased,but brain-derived neurotrophic factor was decreased after SCS.Intrathecal minocycline(1μg-100μg),which inhibits microglial activation,dosedependently attenuated the mechanical hypersensitivity.Pretreatment with low-dose minocycline(1μg,30 min)prolonged the SCS-induced pain inhibition.These findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain.

Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury

Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 m A and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers.

Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

Previous studies on the mechanisms of peripheral nerve injury(PNI)have mainly focused on the pathophysiological changes within a single injury site.However,recent studies have indicated that within the central nervous system,PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels.Therefore,the basic mechanisms of PNI have not been comprehensively understood.Although electrical stimulation was found to promote axonal regeneration and functional rehabilitation after PNI,as well as to alleviate neuropathic pain,the specific mechanisms of successful PNI treatment are unclear.We summarize and discuss the basic mechanisms of PNI and of treatment via electrical stimulation.After PNI,activity in the central nervous system(spinal cord)is altered,which can limit regeneration of the damaged nerve.For example,cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration.The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI.This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission.The injured site of the peripheral nerve is also an important factor affecting post-PNI repair.After PNI,the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site.A slow speed of axon regeneration leads to low nerve regeneration.Therefore,it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site.From the perspective of target organs,long-term denervation can cause atrophy of the corresponding skeletal muscle,which leads to abnormal sensory perception and hyperalgesia,and finally,the loss of target organ function.The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping,addressing the excessive excitability of the dorsal root ganglion,alleviating neuropathic pain,improving neurological function,and accelerating nerve regeneration.Electrical stimulation of target organs can reduce the atrophy of denervated skeletal muscle and promote the recovery of sensory function.Findings from the included studies confirm that after PNI,a series of physiological and pathological changes occur in the spinal cord,injury site,and target organs,leading to dysfunction.Electrical stimulation may address the pathophysiological changes mentioned above,thus promoting nerve regeneration and ameliorating dysfunction.

Electrical stimulation of dog pudendal nerve regulates the excitatory pudendal-to-bladder reflex

Pudendal nerve plays an important role in urine storage and voiding.Our hypothesis is that a neuroprosthetic device placed in the pudendal nerve trunk can modulate bladder function after suprasacral spinal cord injury.We had confirmed the inhibitory pudendal-to-bladder reflex by stimulating either the branch or the trunk of the pudendal nerve.This study explored the excitatory pudendal-to-bladder reflex in beagle dogs,with intact or injured spinal cord,by electrical stimulation of the pudendal nerve trunk.The optimal stimulation frequency was approximately 15–25 Hz.This excitatory effect was dependent to some extent on the bladder volume.We conclude that stimulation of the pudendal nerve trunk is a promising method to modulate bladder function.

Minimally invasive interventional therapy for pain

Pain interventional therapy,known as the most promising medical technology in the 21st century,refers to clinical treatment technology based on neuroanatomy,neuroimaging,and nerve block technology to treat pain diseases.Compared with traditional destructive surgery,interventional pain therapy is considered a better and more economical choice of treatment.In recent years,a variety of minimally invasive pain interventional therapy techniques,such as neuroregulation,spinal cord electrical stimulation,intervertebral disc ablation,and intrasheath drug infusion systems,have provided effective solutions for the treatment of patients with post-herpetic neuralgia,complex regional pain syndrome,cervical/lumbar disc herniation,and refractory cancer pain.

Effects of medically generated electromagnetic interference from medical devices on cardiac implantable electronic devices: A review

As cardiac implantable electronic devices(CIED)become more prevalent,it is important to acknowledge potential electromagnetic interference(EMI)from other sources,such as internal and external electronic devices and procedures and its effect on these devices.EMI from other sources can potentially inhibit pacing and trigger shocks in permanent pacemakers(PPM)and implantable cardioverter defibrillators(ICD),respectively.This review analyzes potential EMI amongst CIED and left ventricular assist device,deep brain stimulators,spinal cord stimulators,transcutaneous electrical nerve stimulators,and throughout an array of procedures,such as endoscopy,bronchoscopy,and procedures involving electrocautery.Although there is evidence to support EMI from internal and external devices and during procedures,there is a lack of large multicenter studies,and,as a result,current management guidelines are based primarily on expert opinion and anecdotal experience.We aim to provide a general overview of PPM/ICD function,review documented EMI effect on these devices,and acknowledge current management of CIED interference.

Current Status of Neuromodulatory Therapies for Disorders of Consciousness

Treatment for disorders of consciousness （DOCs） is still a Gordian knot. Evidence-based guidelines on the treatment of DOC patients are not currently available, while neuromodulation techniques are seen as a potential treatment. Multiple neuromodulation therapies have been applied. This article reviews the most relevant studies in the literature in order to describe a clear picture of the current state of neuromodulation therapies that could be used to treat DOC patients. Both invasive and noninvasive brain stimulation is discussed. Significant behavioral improvements in prolonged DOCs under neuromodulation therapies are rare. The efficacy of various such therapies remains a matter of debate. Further clinical investigations of existing techniques in larger samples properly controlling for spontaneous recovery are needed, and new approaches are awaited.