Noninvasive Evaluation of Nerve Conduction in Small Diameter Fibers in the Rat

Zotova, Elena; Arezzo, Joseph C.

doi:10.1155/2013/254789

Cited by 19 publications

(13 citation statements)

References 97 publications

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“…We extrapolated these values to model 1 μm axons due to a lack of published data on the ultrastructure of small myelinated fibres, resulting in 15 myelin lamellae, and lengths of 1, 3, 5, and 83 μm and axonal diameters of 0.7, 0.7, 0.8, and 0.8 μm for the node of Ranvier, paranodal, juxtaparanodal, and internodal segments, respectively. The 1 and 2 μm model axons had conduction speeds of 4.0 and 8.4 m/s, respectively, consistent with measured values [42–44]. …”

Section: Methodssupporting

confidence: 86%

Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals

2017

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Objective There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics’ vBloc® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. Approach We developed a two-part computational model, coupling a three-dimensional finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 μm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5 to 20 kHz), amplitudes (1 to 8 mA), and electrode designs. Main results We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed “re-excitation”, arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Significance Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our results indicate that compound neural or downstream muscle force recordings may be unreliable as quantitative measures of neural activity for in vivo studies or as biomarkers in closed-loop clinical devices.

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Section: Methodssupporting

confidence: 86%

Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals

2017

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“…Furthermore, they can maintain muscle tone and nerve stimulation of facial muscles which is essential for patients with BP. Physiotherapy techniques that aim to retrain the muscles help prevent the formation of muscle contractures and prevent atrophy of the facial muscles [5][6] . The aim of this literature review was to study in the modern literature the effect of different physiotherapy interventions to treat and improve the symptoms of BP.…”

Section: Introductionmentioning

confidence: 99%

Physiotherapy management of Bell’s palsy - A review of evidenced based physiotherapy practice

Gatidou¹,

Kottaras²,

Lytras³

et al. 2021

Int. J. Adv. Res. Med.

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Bell's palsy (BP) or otherwise known as idiopathic facial nerve palsy is a form of paralysis or weakness of one side of the face. Physiotherapy interventions accelerate recovery, improve facial function and reduce the occurrence of complications. The aim of this review was to study in the modern literature the effect of different physiotherapy interventions for the treatment and improvement of BP symptoms. Method: We reviewed the literature in all modern databases, for the period 2015 -2021, for studies related to the effect of different physiotherapy interventions on the symptoms of patients with BP. Inclusion criteria were: to refer to patients with BP, to contain experimental and control groups and the studies to be clinical trials. Results: Out of the 114 papers that included in their title and abstract the search terms, only 10 were included in our literature review. In the studies, the average sample was 41.2 patients with a distribution of 10 to 94 individuals. Conclusions: The results of the studies showed a great improvement of the facial function, faster recovery and in particular an improvement of the facial symmetry when a program of the Proprioceptive Neuromuscular Facilitation (PNF) method or the Kabat technique is applied in combination with nerve stimulation. In general, facial exercises seem to play an important role in improving the functioning of facial muscles when combined with other techniques or methods, while the application of acupressure massage seems to significantly reduce the underlying symptoms of paralysis and help improve the affected side.

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“…At the more granular level, there are comprehensive reviews of non-clinical CNS models for seizure (Bassett et al, 2014;Easter et al, 2009;Metea et al, 2015;Fonck et al, 2015) and drug abuse liabilities (Kallman, 2015;Moser et al, 2010;Porsolt et al, 2002" O"Connor et al, 2011, with consideration of specific screening models for seizure (Authier et al, 2009;Koseki et al, 2014), sleep (Authier et al, 2014) and peripheral nerve function (Zotova & Arezzo, 2013). However, current industry A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT Authier et al 2015JPTM 6/2/2016 practices and trends as they relate to the use of these models in drug development are not well characterized (Lindgren et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Safety Pharmacology Investigations on the Nervous System: An Industry Survey

Authier

2017

Journal of Pharmacological and Toxicological Methods

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Abstract:The Safety Pharmacology Society (SPS) conducted an industry survey in 2015 to identify industry practices as they relate to central, peripheral and autonomic nervous system ("CNS") drug safety testing. One hundred fifty-eight (158) participants from Asia (16%), Europe (20%) and North America (56%) responded to the survey. 52% of participants were from pharmaceutical companies (>1,000 employees). Oncology (67%) and neurology/psychiatry (66%) were the most frequent target indications pursued by companies followed by inflammation (48%), cardiovascular (43%), metabolic (39%), infectious (37%), orphan (32%) and respiratory (29%) diseases. Seizures (67% of participants), gait abnormalities (67%), tremors (65%), emesis (56%), sedation (52%) and salivation (47%) were the most commonly encountered CNS issues in pre-clinical drug development while headache (65%), emesis/nausea (60%), fatigue (51%) and dizziness (49%) were the most frequent issues encountered in Phase I clinical trials. 54% of respondents reported that a standard battery of tests applied to screen drug candidates was the approach most commonly used to address nonclinical CNS safety testing. A minority (14% of all participants) reported using electroencephalography (EEG) screening prior to animal inclusion on toxicology studies. The most frequent group size was n=8 for functional observation battery (FOB), polysomnography and seizure liability studies. FOB evaluations were conducted in a dedicated room (78%) by blinded personnel (66%) with control for circadian cycle (55%) effects (e.g., dosing at a standardized time; balancing time of day across treatment groups). The rat was reported as the most common species used for seizure liability, nerve conduction and drug-abuse liability testing.

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Noninvasive Evaluation of Nerve Conduction in Small Diameter Fibers in the Rat

Cited by 19 publications

References 97 publications

Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals

Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals

Physiotherapy management of Bell’s palsy - A review of evidenced based physiotherapy practice

Safety Pharmacology Investigations on the Nervous System: An Industry Survey

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