Nerve Conduction Block Research Articles

Diagnostic approach to peripheral neuropathy

Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx) tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG). EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block) and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG). Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF) examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.

Pure neural leprosy: steroids prevent neuropathy progression

Multidrug therapy (MDT), with rifampicin, dapsone, and clofazimine, treats leprosy infection but is insufficient in arresting or preventing the nerve damage that causes impairments and disabilities. This case-series study evaluates the benefits of the combined use of steroids and MDT in preventing nerve damage in patients with pure neural leprosy (PNL). In addition to MDT, 24 patients (88% male aged 20-79 years, median=41) received a daily morning dose of 60 mg prednisone (PDN) that was gradually reduced by 10 mg during each of the following 5 months. PNL was clinically diagnosed and confirmed by nerve histopathology or PCR. A low prevalence (8.3%) of reaction was observed after release from treatment. However, most of the clinical parameters showed significant improvement; and a reduction of nerve conduction block was observed in 42% of the patients. The administration of full-dose PDN improved the clinical and electrophysiological condition of the PNL patients, contributing to the prevention of further neurological damage.

Effects of high‐intensity focused ultrasound on nerve conduction

The effects of various exposures (intensity, duration) of high-intensity focused ultrasound (HIFU) on sciatic nerve conduction were investigated in vivo in rats. The objective was to identify HIFU exposures that produce biological effects ranging from partial to complete conduction block, indicating potential use of HIFU as an alternative to current clinical methods of inducing nerve conduction block. In the study, 26 nerves were exposed and treated with 5-s applications of 5.7-MHZ HIFU with acoustic intensities of 390, 2,255, 3,310, and 7,890 W/cm(2) (spatial peak, temporal peak). Compound muscle action potentials (CMAPs), in response to electrical stimulation of the nerve proximal to the HIFU site, were recorded from the plantar foot muscles immediately before and after HIFU treatment and 2 and 4 h after treatment. Furthermore, a preliminary long-term investigation was performed on 27 nerves with the same four sets of HIFU parameters. CMAPs were measured at the survival endpoint for each animal (7 or 28 days after treatment). For nerves treated with the three lower exposures, CMAPs decreased initially within 4 h or 7 days after HIFU treatment and then recovered to their baseline level at 28 days after treatment. For the highest exposure, however, CMAPs remained absent even 28 days after treatment. These exposure-dependent effects of HIFU on nerve function suggest its future potential as a novel treatment for severe spasticity and pain.

Effects of ramped amplitude waveforms on the onset response of high-frequency mammalian nerve block

Though high-frequency alternating current (HFAC) can block nerve conduction, the block is invariably preceded by an onset response which is a period of repetitive nerve firing. We tested the hypothesis that slowly ramping up the amplitude of the HFAC waveform could produce block without this initial onset response. Computer simulations were performed, using the McIntyre–Richardson–Grill (MRG) model of myelinated mammalian axon. A ramped-amplitude HFAC was applied to axons of diameters ranging from 7.3 µm to 16 µm and at frequencies ranging from 3125 Hz to 40 kHz. The ramped-amplitude HFAC was also investigated in vivo in preparations of rat sciatic nerve. Sinusoidal voltage-regulated waveforms, at frequencies between 10 kHz and 30 kHz, were applied with initial amplitudes of 0 V, linearly increasing with time to 10 V. Ramp durations ranged from 0 s to 60 s. In both the MRG model simulations and the experiments, ramping the HFAC waveform did not eliminate the onset response. In the rat experiments, the peak amplitude of the onset response was lessened by ramping the amplitude, but both the onset response duration and the amount of onset activity as measured by the force-time integral were increased.

Transient facial nerve palsy after topical papaverine application during vestibular schwannoma surgery

✓Some evidence in the literature supports the topical application of papaverine to the cochlear nerve to prevent internal auditory artery vasospasm and cochlear ischemia as a method of enhancing the ability to preserve hearing during acoustic neuroma surgery. The authors report a case of transient facial nerve palsy that occurred after papaverine was topically applied during a hearing preservation acoustic neuroma removal. A 58-year-old woman presented with tinnitus and serviceable sensorineural hearing loss in her right ear (speech reception threshold 15 dB, speech discrimination score 100%). Magnetic resonance imaging demonstrated a 1.5-cm acoustic neuroma in the right cerebellopontine angle (CPA). A retrosigmoid approach was performed to achieve gross-total resection of the tumor. During tumor removal, a solution of 3% papaverine soaked in a Gelfoam pledget was placed over the cochlear nerve. Shortly thereafter, the quality of the facial nerve stimulation deteriorated markedly. Electrical stimulation of the facial nerve did not elicit a response at the level of the brainstem but was observed to elicit a robust response more peripherally. There were no changes in auditory brainstem responses. Immediately after surgery, the patient had a House–Brackmann Grade V facial palsy on the right side. After several hours, this improved to a Grade I. At the 1-month follow-up examination, the patient exhibited normal facial nerve function and stable hearing. Intracisternal papaverine may cause a transient facial nerve palsy by producing a temporary conduction block of the facial nerve. This adverse effect should be recognized when topical papaverine is used during CPA surgery.

Transient facial nerve palsy after topical papaverine application during vestibular schwannoma surgery

Some evidence in the literature supports the topical application of papaverine to the cochlear nerve to prevent internal auditory artery vasospasm and cochlear ischemia as a method of enhancing the ability to preserve hearing during acoustic neuroma surgery. The authors report a case of transient facial nerve palsy that occurred after papaverine was topically applied during a hearing preservation acoustic neuroma removal. A 58-year-old woman presented with tinnitus and serviceable sensorineural hearing loss in her right ear (speech reception threshold 15 dB, speech discrimination score 100%). Magnetic resonance imaging demonstrated a 1.5-cm acoustic neuroma in the right cerebellopontine angle (CPA). A retrosigmoid approach was performed to achieve gross-total resection of the tumor. During tumor removal, a solution of 3% papaverine soaked in a Gelfoam pledget was placed over the cochlear nerve. Shortly thereafter, the quality of the facial nerve stimulation deteriorated markedly. Electrical stimulation of the facial nerve did not elicit a response at the level of the brainstem but was observed to elicit a robust response more peripherally. There were no changes in auditory brainstem responses. Immediately after surgery, the patient had a House-Brackmann Grade V facial palsy on the right side. After several hours, this improved to a Grade I. At the 1-month follow-up examination, the patient exhibited normal facial nerve function and stable hearing. Intracisternal papaverine may cause a transient facial nerve palsy by producing a temporary conduction block of the facial nerve. This adverse effect should be recognized when topical papaverine is used during CPA surgery.

Kombiniertes Auftreten von amyotropher Lateralsklerose und Multipler Sklerose

The concurrence of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is extremely rare. We report on a 55-year-old female patient presenting with a progressive gait disorder for 6 months and a speech disorder for 3 months. Neurological examination revealed a spastic paraparesis and mild dysarthria and dysphagia. Technical and laboratory investigations met the diagnostic criteria for MS: magnetic resonance imaging showed multiple periventricular white matter and cervical lesions; cerebrospinal fluid showed a typical autoimmune response. Within the following 3 months generalized fasciculations, atrophy of the small hand muscles and bulbar signs were noticed. Nerve conduction studies revealed acute and chronic signs of denervation in all limbs without nerve conduction block. Hence clinical and paraclinical examination met the El Escorial criteria for ALS. Although myelitic lesions in the anterior horn cells may lead to peripheral segmental denervation, the generalized denervation suggested the unusual coincident combination of ALS and MS in this patient. In clinical praxis motoneuron diseases should also be considered in patients with pronounced peripheral denervations once "definite" MS has been diagnosed.

Free-flow oxygen delivery using a T-piece resuscitator

<h3>Objective:</h3> To evaluate the likelihood of response to IV immunoglobulin (IVIg) by studying consecutive patients presenting with progressive, asymmetric, pure lower motor neuron (LMN) limb weakness, and to determine the...

Influence of frequency and temperature on the mechanisms of nerve conduction block induced by high-frequency biphasic electrical current

The influences of stimulation frequency and temperature on mechanisms of nerve conduction block induced by high-frequency biphasic electrical current were investigated using a lumped circuit model of the myelinated axon based on Schwarz and Eikhof (SE) equations. The simulation analysis showed that a temperature-frequency relationship was determined by the axonal membrane dynamics (i.e. how fast the ion channels can open or close.). At a certain temperature, the axonal conduction block always occurred when the period of biphasic stimulation was smaller than the action potential duration (APD). When the temperature decreased from 37 to 15 degrees C, the membrane dynamics slowed down resulting in an APD increase from 0.4 to 2.4 ms accompanied by a decrease in the minimal blocking frequency from 4 to 0.5 kHz. The simulation results also indicated that as the stimulation frequency increased the mechanism of conduction block changed from a cathodal/anodal block to a block dependent upon continuous activation of potassium channels. Understanding the interaction between the minimal blocking frequency and temperature could promote a better understanding of the mechanisms of high frequency induced axonal conduction block and the clinical application of this method for blocking nerve conduction.

Self-consistent analyses for potential conduction block in nerves by an ultrashort high-intensity electric pulse

Simulation studies are presented that probe the possibility of using high-field (> 100 kV/cm) , short-duration ( approximately 50 ns) electrical pulses for nonthermal and reversible cessation of biological electrical signaling pathways. This would have obvious applications in neurophysiology, clinical research, neuromuscular stimulation therapies, and even nonlethal bioweapons development. The concept is based on the creation of a sufficiently high density of pores on the nerve membrane by an electric pulse. This modulates membrane conductance and presents an effective "electrical short" to an incident voltage wave traveling across a nerve. Net blocking of action potential propagation can then result. A continuum approach based on the Smoluchowski equation is used to treat electroporation. This is self-consistently coupled with a distributed circuit representation of the nerve dynamics. Our results indicate that poration at a single neural segment would be sufficient to produce an observable, yet reversible, effect.

Multifocal motor neuropathy with abrupt onset and spontaneous recovery

Sirs: Multifocal motor neuropathy (MMN) is characterized by asymmetric weakness without sensory disturbances, with muscle wasting and fasciculations. It has a slowly, stepwise progressive course. Electrophysiological studies show partial or persistent motor conduction blocks [1]. Although unilateral wrist drop or grip weakness can be a presenting symptom in MMN, an acute onset and almost full recovery within a few days has not yet been described. A 34 year old man presented with abrupt, painless onset of weakness of his right hand. On examination he only had distal weakness of the right arm: strength in finger and wrist extensors 3/5, abductor pollicis brevis and opponens pollicis 4/5, and intrinsic muscle function 4/5 (MRC). Sensory examination was normal. The deep tendon reflexes were brisk and symmetric, the plantar reflex normal on both sides. Ancillary investigations including MRI imaging of the brain were unremarkable. Nerve conduction studies of the right arm were normal. There was an almost full recovery within 5 days, except for a slight impairment of right-sided rapid finger movements. During three years of follow-up his minor signs remained stable. Then he noticed a gradually progressive weakness of the right arm and left leg. He complained of cramps in the abdominal muscles and all four limbs. Examination revealed fasciculations in the both abductor pollicis brevis and distal weakness of his right arm comparable with the examination three years previously. Additionally there was weakness of the left foot flexors and extensors(4/5). Sensory testing was normal. Deep tendon reflexes had become hypoactive at the right arm and absent at both ankles. Extensive nerve conduction studies showed a bilateral partial motor conduction block of the median nerve in the lower arm, and a complete motor conduction block in the left peroneal nerve. Motor and sensory nerve conduction velocities, distal latencies, and F-waves were within normal values. IgM anti-GM1 antibodies were present (1 : 100). CSF analysis showed 3 white cells and total protein was 0.49 g/L. The diagnosis of MMN was made and the patient was treated with 2 g/kg intravenous immunoglobulin (IVIg) in two days. He showed a clear improvement after IVIg starting within four days after onset of the infusion . Within two weeks there was an almost complete recovery with only slight weakness of finger extension at the right and normal strength of left foot. There was a relapse after three weeks, which again responded to IVIg. He presently still needs 80 g of IVIg every 4 weeks to avoid full relapses between treatments. MMN is a chronic demyelinating neuropathy. It is characterized by slowly progressive asymmetrical weakness of the limbs without sensory involvement [2]. The diagnosis of MMN is based on clinical, laboratory and electrophysiological characteristics [2]. The distinguishing electrophysiological characteristics are the presence of multifocal motor conduction blocks outside the usual sites of nerve compression [3–4]. These results of electrophysiological testing and the normal CSF protein are not compatible with the diagnosis chronic inflammatory demyelinating polyneuropahty (CIPD). This patient’s history illustrates that MMN can present with abrupt onset of weakness of one limb and rapid, spontaneous and almost complete recovery. Although the asymmetry is often remarkable in MMN, both limbs are usually involved. The patient had multifocal motor weakness, however, without a clear distribution of a multiple mononeuropathy, the more frequent distribution pattern in MMN. Slow spontaneous remissions in MMN have been reported [5], but a spontaneous recovery within a few days has not yet been described.

Peculiarities of nerve conduction block produced by lidocaine and ajmaline

The development of tonic and use-dependent block of nerve conduction under the effect of antiarrhythmic drug ajmaline and local anesthetic lidocaine was examined on sciatic nerve of Rana ridibunda. Ajmaline and lidocaine attenuated the amplitude of action potential by half during 120 and 13 minutes, respectively. Ajmaline produced virtually immediate use-dependent block of conductance, while it was minor in lidocaine-treated nerve preparation.

A new method for the estimation of motor nerve conduction block

Objective A method for conduction block (CB) estimation, based on compound muscle action potentials (CMAP) elicited by stimulation at sites proximal and distal to the region in which a block is suspected, which is less sensitive to temporal dispersion than methods based on area and amplitude estimation, routinely used in clinical practice. Methods The method is based on deconvolution of CMAPs. It provides the delay distribution that convolved with a kernel (estimated by an optimisation method) gives a reconstruction of the CMAPs. The integral of the delay distribution was used to estimate CB. The method was tested on phenomenological signals (sum of delayed and amplitude scaled versions of the same signal), structure based simulated signals (from a plane layer generation model of surface EMG), and experimental signals (eight healthy subjects; CMAPs recorded over abductor digiti minimi; different temporal dispersions obtained comparing above-elbow stimulation of ulnar nerve with below-elbow stimulation or with wrist stimulation; conduction distances about 10 and 35 cm, respectively). Results Deconvolution method gives more precise estimates of the simulated CB with respect to area and amplitude methods (phenomenological signals: bias in CB estimation in the worst case about 10% for deconvolution, 30% for area, 60% for amplitude). Experimental data: by increasing temporal dispersion, in the average CB estimation increases 4% for area and 10% for amplitude, no increase for deconvolution. Conclusions The new method for CB estimation is less sensitive to temporal dispersion than area and amplitude methods. Significance The proposed method provides a precise CB estimation. Being stable to temporal dispersion, it allows to diagnose CB with a lower confidence threshold than in the case of area and amplitude.

Tramadol produces nerve conduction block in a manner independent of opioid receptor activation and monoamine uptake inhibition

Tramadol produces nerve conduction block in a manner independent of opioid receptor activation and monoamine uptake inhibition

Quantitative sensory testing of cold and vibration perception during compression of median nerve at the wrist

We conducted a sequential study of quantitative sensory testing (QST) during compression-induced conduction block of the median nerve to determine relative vulnerability of the small and large myelinated nerve fibers. We tested cold (CPT) and vibratory perception thresholds (VPT) of the third digit in 15 healthy subjects during constant, localized compression for 30 min of the median nerve at the wrist. The orthodromic sensory nerve action potentials (SNAPs) recorded at wrist and elbow served to monitor the degree of associated conduction block. After the onset of nerve compression, it took 16 min for CPT to show the first change; VPT remained normal for 26 min. CPT recovered 2 min later than VPT after release of compression. The SNAP amplitude at the wrist diminished immediately at the start of compression and declined progressively, whereas the response at the elbow remained the same initially, showing no latency change for 20 min. A nearly identical time course of SNAP changes in the two experiments justified the comparison of separately tested CPT and VPT as a measure of modality-specific vulnerability. Contrary to the common belief, a focal compression sufficient to produce rapidly reversible conduction abnormalities affects the slow-conducting small myelinated fibers mediating cold perception before the fast-conducting large myelinated fibers transmitting vibration perception. The data document the order of modality-specific vulnerability of sensory nerve fibers to mild compression. The finding suggests that testing CPT, rather than VPT, provides a better QST to delineate rapidly reversible symptoms induced by compression.

Ulnar Nerve Compression in the Cubital Tunnel by an Epineural Ganglion: A Case Report

Epineural ganglia are considered to be a usual cause of peripheral nerve compression. In this report, we present a rare case of ulnar nerve compression by an epineural ganglion in the cubital tunnel. A 28-year-old right-handed female secretary developed progressive pain, numbness, and weakness in her right elbow, forearm, and hand for 6 months. Atrophy of the adductor pollicis and the first dorsal interosseous muscles was apparent. Clinical examination revealed a cystic mass at the posterior side of the elbow. Magnetic resonance imaging identified a ganglion while electrophysiologic studies revealed a severe conduction block of the ulnar nerve at the elbow. During surgery a 2-cm diameter epineural ganglion was identified compressing the ulnar nerve and was excised using microsurgery techniques. Two months postoperatively, the clinical recovery of the patient was very satisfactory, although the postoperative electrophysiologic studies demonstrated a less dramatic improvement.

Mechanism of Nerve Conduction Block Induced by High-Frequency Biphasic Electrical Currents

The mechanisms of nerve conduction block induced by high-frequency biphasic electrical currents were investigated using a lumped circuit model of the myelinated axon based on Frankenhaeuser-Huxley (FH) model or Chiu-Ritchie-Rogart-Stagg-Sweeney (CRRSS) model. The FH model revealed that the constant activation of potassium channels at the node under the block electrode, rather than inactivation of sodium channels, is the likely mechanism underlying conduction block of myelinated axons induced by high-frequency biphasic stimulation. However, the CRRSS model revealed a different blocking mechanism where the complete inactivation of sodium channels at the nodes next to the block electrode caused the nerve conduction block. The stimulation frequencies to observe conduction block in FH model agree with the observations from animal experiments (greater than 6 kHz), but much higher frequencies are required in CRRSS model (greater than 15 kHz). This frequency difference indicated that the constant activation of potassium channels might be the underlying mechanism of conduction block observed in animal experiments. Using the FH model, this study also showed that the axons could recover from conduction block within 1 ms after termination of the blocking stimulation, which also agrees very well with the animal experiments where nerve block could be reversed immediately once the blocking stimulation was removed. This simulation study, which revealed two possible mechanisms of nerve conduction block in myelinated axons induced by high-frequency biphasic stimulation, can guide future animal experiments as well as optimize stimulation waveforms for electrical nerve block in clinical applications.

Generalized Peripheral Nerve Failure During Thoracic Spine Surgery: A Case Report

Intra-operative systemic changes impairing peripheral nerve function are not commonly detected with electrophysiology. This case presentation illustrates how somatosensory evoked potential (SSEP) monitoring can detect global changes in peripheral nerve excitability during spine surgery. A posterior thoracic spine fixation was performed on a young male with multiple traumatic injuries. Bilateral tibial nerve SSEPs were intraoperatively recorded, along with the right median nerve SSEP for control. A rapid, progressive loss of tibial and median nerve potentials (followed by cortical SSEP loss) occurred 90 min after anaesthetic induction. Oxygenation and fluid volume were adequate throughout the case, despite mean airway resistance being elevated (33 cmH(2)0) and blood pressure being low (80/45 mmHg). Corresponding to the decrease in peripheral nerve responses was a drop in end-tidal CO(2) partial pressure (PaCO(2)) from 37 to 25 mmHg. Approximately, 100 min later, the peripheral and cortically generated SSEPs recovered in 2 of 3 limbs monitored. On emergence from anesthesia it was clear that the patient had bitten and kinked the endotracheal tube thus increasing the airway resistance. Ventilation difficulties were magnified with the patient's prone position. Post-operatively there were no sensorimotor deficits. Somatosensory evoked potential monitoring during spine surgery can detect uncommon generalized nerve conduction block, and further alert surgical teams to a systemic impairment. This was discovered to result from a compromised endotracheal tube. This can apply in various monitoring situations, as the changes affecting the SSEPs were not related to surgical manipulation.

Clinical and electrophysiological predictors of respiratory failure in Guillain-Barré syndrome: a prospective study

Respiratory failure is the most serious short-term complication of Guillain-Barré syndrome and can require invasive mechanical ventilation in 20-30% of patients. We sought to identify clinical and electrophysiological predictors of respiratory failure in the disease. We prospectively assessed electrophysiological data and clinical factors, including identified predictors of delay between disease onset and admission, inability to lift head, and vital capacity, in patients admitted with Guillain-Barré syndrome. We related these factors to subsequent need for ventilatory support. Neurophysiological findings were classified as demyelinating, axonal, equivocal, unexcitable, or normal. Predictive values of clinical and electrophysiological data were tested using classification trees to build up a predictive model. This model was initially built up in a two-third (fitting set) then validated in a one-third (validation set) of the total sample. The fitting and validation sets were randomly selected. We also assessed the predictive value of this model for disability at 6 months. From 1998, to 2006, 154 patients with Guillain-Barré syndrome were included in the study and 34 (22%) were subsequently ventilated. Demyelinating Guillain-Barré syndrome was more common in patients who went on to be ventilated than in those who were not (85%vs 51%, p=0.0003). Vital capacity and the proximal/distal compound muscular amplitude potential (p/dCMAP) ratio of the common peroneal nerve were retained in the tree model, with a probability of needing ventilation of less than 2.5% in patients with a ratio of greater than 55.6% and a vital capacity more than 81% of predicted. A p/dCMAP ratio of the peroneal nerve less than 55.6% and age older than 40 years were retained as independent predictors of disability at 6 months. Neurophysiological testing is helpful for assessing risk of respiratory failure, which is highest in patients with evidence of demyelination and very low in those without both 55.6% conduction block of the common peroneal nerve and a 20% reduction in vital capacity.

Image-Guided High-Intensity Focused Ultrasound for Conduction Block of Peripheral Nerves

The objective of our work has been to investigate the use of ultrasound image-guided high-intensity focused ultrasound (HIFU) to non-invasively produce conduction block in rabbit sciatic nerves in vivo, a technique that could become a treatment of spasticity and pain. The work reported here involved the investigation of the duration of such conduction blocks after HIFU treatment and whether they resulted in axon degeneration. The right sciatic nerves of 12 rabbits were treated, under guidance of ultrasound imaging, with repeated 5-s applications of 3.2 MHz HIFU with in situ intensity of 1930 W/cm(2) (spatial-average, temporal-average) until conduction block was achieved. Survival endpoints were 0, 7, or 14 days after HIFU treatment, at which point the nerve conduction was assessed. Qualitative and quantitative histological analysis of nerve sections proximal and distal to the HIFU site was performed. Conduction block of all 12 nerves was achieved with average HIFU treatment time of 10.5+/-4.9 s (mean+/-SD). The volume of necrosis of adjacent muscle was measured to be 1.59+/-1.1 cm(3) (mean+/-SD). For all nerves, conduction block remained at the survival endpoint and the block resulted in degeneration of axons distal to the HIFU site, as confirmed by electrophysiological and histological methods. Potential clinical applications include treatment of spasticity in patients with spinal cord injury or pain in cancer patients.