Previous studies have suggested that sympathetic sprouting in the periphery may contribute to the development and persistence of sympathetically-maintained pain in animal models of neuropathic pain. The purpose of this thesis was to examine morphological changes in the cutaneous innervation in rats after chronic constriction injury (CCI) to the sciatic nerve. More specifically, this study addresses the question of whether sympathetic fibres sprout de novo into the upper dermis of the rat hindpaw skin after CCI of the sciatic nerve. We also determined changes in peptidergic sensory innervation following CCI. / At several periods post-injury, hind paw skin was harvested and processed using a monoclonal antibody against dopamine-beta-hydroxylase to detect sympathetic fibres and a polyclonal antibody against calcitonin gene-related peptide to identify peptidergic sensory fibres. We observed migration and branching of sympathetic fibres into the upper dermis of the hind paw skin, from where they were normally absent. This migration was first detected at 2 weeks, peaked at 4 to 6 weeks and lasted for at least 20 weeks post-lesion. At 8 weeks post-lesion, there was a dramatic increase in the density of peptidergic fibres in the upper dermis. Quantification revealed that densities of peptidergic fibres 8 weeks post-lesion were significantly above levels of sham animals. Interestingly, the ectopic sympathetic fibres did not innervate blood vessels but formed a novel association and wrapped around sprouted peptidergic nociceptive fibres. Our data show a long-term sympathetic and sensory innervation change in the rat hind paw skin after the chronic constriction injury. This novel fibre arrangement after nerve lesion may play an important role in the development and persistence of sympathetically-maintained neuropathic pain after partial nerve lesions.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Orientador: Antonio Augusto Fasolo Quevedo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação / Made available in DSpace on 2018-08-21T20:36:43Z (GMT). No. of bitstreams: 1 Ferri_CarlosAlexandre_M.pdf: 3581178 bytes, checksum: 205686fbe0768dc0e89e77aa54ae670f (MD5) Previous issue date: 2012 / Resumo: Nas últimas décadas, o uso de estimuladores de nervos periféricos tem sido disseminado entre os médicos anestesiologistas. Esses equipamentos ajudam a posicionar a agulha com maior precisão em bloqueios periféricos, reduzindo o risco de lesões nos nervos, melhorando a qualidade dos bloqueios e minimizar a necessidade de doses complementares de anestésico. Contudo, os equipamentos atuais necessitam que o usuário ajuste manualmente a intensidade do estímulo. Deste modo, na maior parte das vezes, o médico necessita da ajuda de outro profissional. Este trabalho objetiva avaliar a aplicabilidade clínica de um estimulador automatizado de nervo periférico, dando total autonomia ao anestesiologista, possibilitando que, mesmo sozinho, possa realizar todos os procedimentos, com auxílio do estimulador, sem dificuldade. O aparelho desenvolvido ajusta automaticamente os níveis de corrente através de um sistema realimentado via acelerometria, permitindo que o anestesiologista se preocupe apenas com a introdução da agulha. Para facilitar o uso pelo médico, as informações em relação à identificação de resposta motora são fornecidas via display LCD e avisos sonoros. Os testes foram realizados em duas etapas: na primeira, o equipamento foi testado em malha aberta (controlado manualmente, como os estimuladores normalmente disponíveis no mercado), pois a finalidade era coletar a resposta muscular, atividade mioelétrica (eletromiografia) e mecânica (acelerometria), evocada pela estimulação nervosa; na segunda, após análise dos dados coletados na etapa anterior (foi escolhido o acelerômetro como melhor técnica para realimentação), o equipamento foi testado com controle automático, a fim de verificar sua eficácia e precisão, quando comparado com o método de controle manual / Abstract: In the last decades, the use of peripheral nerve stimulators has been broadcast among anesthesiologists. This equipment help placing the needle with greater accuracy in the peripheral block, reducing the risk of nerve damage to the nerves, improving the quality of peripheral nerve blocks and minimizing the need for additional doses of anesthetics. However, cur-rent equipment requires the user to manually adjust the intensity of the stimulus. Thus, in most cases, the doctor needs help from other professional. This study aims to evaluate the clinical applicability of an automated peripheral nerve stimulator, giving full autonomy to the anesthesiologist, enabling him or her, even alone, to perform all procedures, with the help of the stimulator, without difficulty. The developed device automatically adjusts the levels of current through a feedback system via accelerometry, allowing the anesthesiologist to worry only about needle in-sertion. For ease of use by the medical staff, the information regarding the identification of motor response is provided via LCD display and warning sounds. Tests were conducted in two phases: first, the equipment was tested in open loop (controlled manually, just like as stimulators usually available on the market), because the purpose was to collect electric (EMG) and mechanical (accelerometry) muscular response evoked by nerve stimulation; in the second phase, after analysis of the data collected in the previous stage (accelerometer was chosen as the best technique for feedback), the equipment was tested with automatic control, to verify its efficiency and accuracy when compared to the manual control method / Mestrado / Engenharia Biomedica / Mestre em Engenharia Elétrica

Sensory transmission was studied in trigeminal root ganglia (TRG) of guinea pigs, using intracellular recording techniques. One approach was to examine in detail the effects of applications of different K⁺-channel blockers on the membrane voltage responses and outward currents of TRG neurons, in order to better understand the fundamental processes that affect their excitabilities and repetitive spike discharge. The second approach was to examine several endogenous substances for their effects on the excitabilities of TRG neurons. In addition, a strategy was developed for electrophysiological recording from neurons in human sympathetic ganglia. Successful investigations of these neurons revealed properties similar to certain reported characteristics of sympathetic neurons in experimental animals, including high (~29 MΩ input resistances, pharmacological sensitivity of spikes to the specific Na⁺-channel blocker tetrodotoxin (TTX, 1 µM) and to selective K⁺-channel blockers -- 4-aminopyridine (4-AP, 1 mM) and tetraethylammonium (TEA, 10 mM). The investigations demonstrated the potential value of these in vitro preparations for studies of the human condition. The investigations in TRG neurons demonstrated that bath applications of TEA (0.1-10 mM) and 4-AP (0.05-5 mM) or Cs⁺ applied internally from the recording electrode, produced an increase in input resistance and a decrease threshold for spike generation in all neurons. Also, applications of 4-AP increased subthreshold oscillations of the membrane potential and enhanced the repetitive spike firing evoked by intracellular injections of current pulses, or elicited spontaneous firing. In contrast, TEA or Cs⁺ applications blocked the oscillations and the spike afterhyperpolarizations (AHPs) without exaggerating repetitive discharge. These investigations suggestedthat several pharmacologically distinct K -currents contribute to the control of excitability in TRG neurons. Comparison of combined actions of 4-AP and TEA with those of Cs⁺, suggested that other ions in addition to K⁺ may contribute to postspike events. Single electrode voltage-clamp analyses revealed transient outward currents that were evoked at the termination of hyperpolarizing voltage commands from holding potentials near -40 mV. The activation was rapid (<5ms) and inactivation (T≃19 ms) complete at potentials within the activation range (-40 to -75 mV). During combined application of TTX (1 µM) and TEA (10 mM), fast activating, sustained currents (>1 s) were evoked by depolarizing commands from holding potentials near -70 mV. These currents were blocked completely by the additional applications of 4-AP (5 mM). Applications of TEA (0.1 mM to 10 mM) produced dose-dependent reductions of the transient outward currents. Applications of Cs⁺ also blocked the currents. However, administrations of 4-AP (0.05 to 5 mM) only slightly reduced these currents and high doses of muscarinic agonists had no effect. The high sensitivity to TEA, and not to 4-AP, suggest a fundamental distinction from similar currents observed previously in other neurons of vertebrates and invertebrates, and hence this transient outward current in TRG neurons, is termed I(T)- The kinetics of I(T) suggest its involvement in the spike AHPs. Therefore, blockade of I(T) by TEA may interfere indirectly with the re-activation of voltage-dependent Na⁺-channels, leading to decreases in repetitive discharge ability. The TEA-insensitive sustained outward current presumably has an inhibiting influence on repetitive discharge. Conditions that interfere with this current, such as blockade of K⁺-channels by 4-AP without a significant blockade of I(T), strongly favour the generation of repetitive discharge in TRG neurons. The investigations using electrical stimulation of axons revealed that changes in the resting potential could inhibit the invasion of spikes into the perikarya, or facilitate the generation of ectopic spike discharges. Applications of 4-AP (1 mM) facilitated the perikaryal invasion of spikes evoked by axonal stimulation, and also resulted in the appearance of fast (~10 ms) depolarizations that reached spike threshold in the absence of applied stimuli. These investigations provided direct evidence that the perikarya of sensory neurons are capable of spike generation, and suggest that this behavior may occur in normal or pathophysiological conditions. The most notable effects of autacoids were those of substance P and histamine, whereas bradykinin did not affect neuronal membrane properties. Applications of substance P in micromolar doses evoked large (up to 45 mV), reversible depolarizations in the majority of neurons, whereas histamine applications produced similar depolarizations only in a small portion of the TRG neurons. Increases in the repetitive discharge abilities of neurons were evident during substance P-induced depolarizations. Studies on the ionic mechanism of substance P action revealed that the peptide-applications resulted in activation of inward currents as well as blockade of outward currents. In addition, it was shown that Na⁺ and Mg²⁺ were involved in the mechanism of action. These findings represent the first demonstration of the profound actions of substance P on the perikaryal membranes of sensory neurons in mammals. The excitatory actions of this endogenous peptide also give rise to the possibility of physiological actions of substance P at multiple sites in the trigeminal system. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Orientadores: Alexandre Leite Rodrigues de Oliveira, Eliana Aparecida de Rezende Duek / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-26T15:35:48Z (GMT). No. of bitstreams: 1 Assaf_Kyl_M.pdf: 4219247 bytes, checksum: 1f0af33b698c2094539d28e23f3f042b (MD5) Previous issue date: 2015 / Resumo: Lesões traumáticas de nervos periféricos podem gerar separação de seus cotos, impossibilitando a neurorrafia término-terminal. Nesses casos, os enxertos autólogos são muito utilizados, mas apresentam algumas desvantagens, como disponibilidade do tecido doador, formação de neuromas dolorosos na área doadora, entre outras. A técnica de tubulização, na qual são empregados tubos para orientar e proteger o nervo durante a regeneração, oferece vantagens como preservação da área doadora e possibilidade de manipulação do ambiente interno do tubo. Muitos aspectos do tubo a ser utilizado para regeneração nervosa devem ser considerados, como sua biocompatibilidade, biodegradabilidade, tempo de degradação, etc. A poli(?-caprolactona) (PCL) é um material que possui tais propriedades. Os nanotubos de carbono (NT1) e o grafeno (NTN) também possuem características que os tornam excelentes dispositivos para implantes neurais e para compor compósitos poliméricos. Neste trabalho, nervos isquiáticos de ratos Lewis foram transeccionados e tubulizados com PCL, PCL com nanotubos de carbono, PCL com óxido de grafeno e PCL com ambas as nanoestruturas. A caracterização dos nanocompósitos mostrou que as nanoestruturas tem boa dispersão, não alteram o grau de cristalinidade do PCL, oferecem reforço na matriz polimérica e provocam alteração na mobilidade molecular na parte amorfa do polímero. Na análise das próteses por microscopia eletrônica de varredura, os tubos NT1, NTN e também os confeccionados com a mistura deles, apresentaram um número importante de células aderidas, quando comparados ao PCL. Todos os materiais também se mostraram biocompatíveis. Na contagem das fibras nervosas e na comparação das áreas dos nervos, a mistura mostrou diferenças estatísticas em relação aos demais grupos experimentais (p<0,05). Porém, nas análises morfométricas não foram observadas diferenças entre os grupos. Ainda, a avaliação funcional dos animais não mostrou uma recuperação significativa da marcha. Contudo, a comparação das massas dos músculos sóleo e tibial anterior e a análise histológica desses, revelaram preservação de massa, sem atrofia das fibras musculares, indicando reinervação bem sucedida / Abstract: Injuries to peripheral nerves generate proximal and distal stumps, usually making end-to-end neurorrhaphy impossible. In such cases, autologous grafts are widely used, but have some disadvantages, such as availability of donor tissue, formation of painful neuromas in the donor area, etc. The tubulization technique, in which tubes are used to guide and protect the nerve during regeneration, offers advantages such as preservation of the donor nerve area and the possibility of manipulating the internal environment of the tube. Many aspects of the conduit to be used for nerve regeneration must be considered as biocompatibility, biodegradability, degradation time, etc. The poly (?-caprolactone) (PCL) is possesses most of these properties. Carbon nanotubes and graphene also have features that make them excellent devices for neural implants and to constitute polymer composites. In this work, sciatic nerves of Lewis rats were transected and tubulized with PCL, PCL with carbon nanotubes (NT1), PCL with graphene oxide (NTN) and PCL with both nanostructures. Nanocomposites characterization showed that nanoparticles have good dispersion, do not alter the degree of PCL crystallinity, provide reinforcement of the polymer matrix and cause changes in the molecular mobility in the amorphous part of the polymer. In the analysis of the prostheses by scanning electron microscopy, NT1, NTN and its mixture showed higher number of adhered cells as compared to the PCL. All materials were also biocompatible. The counting regenerated nerve fibers and comparison of the nerve areas, the mixture showed statistical differences when compared to the other experimental groups (p <0.05). Nevertheless, morphometric analyzes were not different among groups. Furthermore, functional evaluation of the animals showed no significant gait recovery after 8 weeks post surgery. However, comparison of the weigth of the soleus and anterior tibialis and the histological analysis revealed absence of atrophy and preservation of the tissue, indicating a successful reinervation / Mestrado / Biologia Celular / Mestra em Biologia Celular e Estrutural

No description available.

Currently there does not exist a type of peripheral nerve interface that adequately combines spatial selectivity, spatial coverage and low invasiveness. In order to address this lack, we investigated the application of bioelectric source localization algorithms, adapted from electroencephalography/magnetoencephalography, to recordings from a 56-contact “matrix” nerve cuff electrode. If successful, this strategy would enable us to improve current neuroprostheses and conduct more detailed investigations of neural control systems. Using forward field similarities, we first developed a method to reduce the number of unnecessary variables in the inverse problem, and in doing so obtained an upper bound on the spatial resolution. Next, a simulation study of the peripheral nerve source localization problem revealed that the method is unlikely to work unless noise is very low and a very accurate model of the nerve is available. Under more realistic conditions, the method had localization errors in the 140 μm-180 μm range, high numbers of spurious pathways, and low resolution. On the other hand, the simulations also showed that imposing physiologically meaningful constraints on the solution can reduce the number of spurious pathways. Both the influence of the constraints and the importance of the model accuracy were validated experimentally using recordings from rat sciatic nerves. Unfortunately, neither idealized models nor models based on nerve sample cross-sections were sufficiently accurate to allow reliable identification of the branches stimulated during the experiments. To overcome this problem, an experimental leadfield was constructed using training data, thereby eliminating the dependence on anatomical models. This new strategy was successful in identifying single-branch cases, but not multi-branches ones. Lastly, an examination of the information contained in the matrix cuff recordings was performed in comparison to a single-ring configuration of contacts. The matrix cuff was able to achieve better fascicle discrimination due to its ability to select among the most informative locations around the nerve. These findings suggest that nerve cuff-based neuroprosthetic applications would benefit from implanting devices with a large number of contacts, then performing a contact selection procedure. Conditions that must be met before source localization approaches can be applied in practice to peripheral nerves were also discussed.

O uso da ultrassonografia na anestesia regional teve um crescimento vertiginoso nos últimos anos, devido ao grande progresso na resolução das imagens ultrassonográficas, permitindo a visibilização não só de vasos, mas de raízes nervosas e nervos periféricos. O objetivo do presente trabalho consistiu na avaliação ultrassonográfica do plexo braquial pela via axilar, bem como a identificação dos nervos em relação a artéria axilar. Foram utilizados 50 animais da espécie canina, sem distinção de raça, sexo e idade. Em todos os animais administrou-se propofol (3 mg/kg) através de um acesso venoso pré-instalado. Os animais foram mantidos sonolentos, porém facilmente despertáveis durante todo o procedimento. Após posicionamento do animal e iniciada a avaliação ultrassonográfica com a identificação das estruturas vasculares e nervosas, foi introduzida uma agulha eletricamente isolada guiada por estimulador de nervo periférico, obtendo-se, assim, resposta motora adequada para cada nervo visualizado por meio de uma corrente estimuladora de 0,5 mA. O exame teve como objetivo identificar a artéria axilar e os nervos radial, mediano e ulnar, e anotar suas posições. Para relacionar os nervos à artéria axilar, a região a ser estudada foi dividida em quatro setores. Em todos os pacientes estudados foram identificados os nervos: mediano localizado na região craniolateral (setor 4) em 8% dos pacientes e na região craniomedial (setor 1) em 92%; nervo radial na região craniomedial (setor 1) em 2% dos pacientes, caudomedial (setor 2) em 92% e caudolateral (setor 3) em 6%; nervo ulnar encontrado na região craniolateral (setor 4) em 2% dos animais e na região craniomedial (setor 1) em 98%. Diante dos resultados, conclui-se que a artéria axilar, na abordagem estudada, facilita a identificação e posicionamento dos nervos com o auxílio do estimulador de nervos periféricos e da ultrassonografia. / The use of ultrasonography in regional anesthesia has grown rapidly in recent years, due to the great progress in the resolution of ultrasound images, allowing the visualization not only of vessels, but of nerve roots and peripheral nerves. The objective of the present study consisted in the ultrasonography evaluation of the brachial plexus by the axillary way, as well as the identification of the nerves in relation to the axillary artery. Fifty animals of the canine species were used, without distinction of race, sex and age. Propofol (3 mg/kg) was given in all animals via pre-installed venous access. The animals were kept drowsy but easily aroused throughout the procedure. After the positioning of the animal and the ultrasound evaluation with the identification of the vascular and nervous structures, an electrically isolated needle guided by a peripheral nerve stimulator was introduced, thus obtaining adequate motor response for each nerve visualized through a stimulating current of 0.5 mA. The objective of the test was to identify the axillary artery and the radial, median and ulnar nerves, and note their positions. To relate the nerves to the axillary artery, the region to be studied was divided into four sectors. In all the patients studied, nerves were identified: median located in the craniolateral region (sector 4) in 8% of patients and in the craniomedial region (sector 1) in 92%; radial nerve in the craniomedial region (sector 1) in 2% of patients, caudomedial (sector 2) in 92% and caudolateral (sector 3) in 6%; ulnar nerve found in the craniolateral region (sector 4) in 2% of the animals and in the craniomedial region (sector 1) in 98%. In view of the results, it was concluded that the axillary artery, in the approach studied, facilitates the identification and positioning of the nerves with the aid of the peripheral nerve stimulator and the ultrasonography.

As consequências mais graves da hanseníase resultam do acometimento neurológico. Recentemente a ultrassonografia (US) têm ganhado importância na avaliação da neuropatia hansênica. O objetivo deste trabalho foi avaliar por US nervos periféricos de pacientes com hanseníase antes e após o tratamento. Buscou-se caracterizar alterações ao diagnóstico e evolução da doença, controlando os efeitos de fatores confundidores e investigando fatores de risco para progressão das alterações (classificação, episódios reacionais, sexo, tempo de evolução). Foram sistematicamente examinados por US os nervos ulnares (regiões pré-túnel cubital UPT e túnel UT), medianos e fibulares comuns bilateralmente para mensuração das áreas de secção transversa (CSA) e cálculo das medidas de assimetria delta CSA (diferença absoluta entre CSAs dos lados direito e esquerdo de cada nervo) e delta Utpt (diferença absoluta entre CSAs de UPT e UT ipsilaterais); também foram analisadas alterações qualitativas (ecogenicidade e Doppler). Foram avaliados 100 pacientes antes do tratamento, sendo 14 paucibacilares (3 indeterminados, 11 tuberculoides) e 86 multibacilares (31 dimorfo-tuberculoides, 34 dimorfo-dimorfos, 13 dimorfo-virchowianos, 8 virchowianos); destes, 73 completaram a avaliação pós-tratamento. Considerando que alterações em pelo menos uma das medidas avaliadas refletem neuropatia, observou-se frequências similares de neuropatia pré-tratamento nos paucibacilares (PB) (35,7 a 57,1%) e multibacilares (MB) (50 a 65,1%). O nervo mais frequentemente acometido nos PB foi o fibular comum, enquanto que nos MB foi o ulnar. As médias de CSA foram maiores nos MB do que nos PB em todos os nervos (p<0,05) e observou-se tendência de maior assimetria (deltas CSA e Utpt) nos MB pré-tratamento. A comparação dos pacientes sem e com alguma reação (tipo 1, tipo 2 e/ou neurite) revelou valores significativamente maiores de CSA, delta CSA e delta Utpt nos pacientes com reações. Constatou-se associação entre presença de sinal Doppler e antecedente de reações (p<0,05). Na avaliação pós-tratamento, nenhum dos fatores de risco foi fortemente relacionado à piora dos achados ultrassonográficos, no entanto algumas análises sugeriram maior risco em pacientes multibacilares (maiores frequências de alterações de CSA nos MB, p>0,05) e com reações hansênicas (odds ratio: 4,67; intervalo de confiança 95%: 1,17-18,64; p<0,05 para alterações de CSA no nervo mediano). Pós-tratamento, os MB apresentaram maior frequência de alterações de ecogenicidade que os PB (p<0,05) e os pacientes sem e com reações apresentaram frequências semelhantes de alterações de ecogenicidade e Doppler, sem aumento significante do odds ratio. O tempo de evolução da doença e o sexo não foram fatores de risco significantes para a progressão das alterações ultrassonográficas. A US demonstrou que o acometimento de nervos periféricos é frequente na hanseníase, independente da classificação e presença de reações. Algumas alterações ultrassonográficas podem não regredir completamente ou mesmo se intensificar apesar do tratamento da infecção. Visto que as consequências mais temidas e estigmatizantes da hanseníase são secundárias à neuropatia, é necessário o aprimoramento de medidas diagnósticas e terapêuticas enfocando o acometimento neurológico. / Leprosy most feared consequences are due to neurological involvement. Recently, ultrasonography (US) is being used to assess imaging findings in leprosy neuropathy. The purpose of this study was to evaluate leprosy patients peripheral nerves using US, before and after treatment. We sought to characterize diagnostic abnormalities and their evolution, controlling the effects of confounding factors and investigating risk factors for progression of US abnormalities (classification, reactions, gender, duration of disease). Ulnar (at pre cubital tunnel area -UPT- and at the tunnel -UT), median and common fibular nerves were systematically and bilaterally scanned in order to measure cross sectional areas (CSA) and to calculate the asymmetry indexes delta CSA (absolute difference between right and left CSAs for each nerve) and delta Utpt (absolute difference between UPT and UT CSAs at the same side). Qualitative abnormalities (echogenicity and Doppler) were also analyzed. One hundred patients underwent US exam before starting treatment: 14 paucibacillary (3 indeterminate, 11 tuberculoid) and 86 multibacillary (31 borderline-tuberculoid, 34 borderline-borderline, 13 borderline-lepromatous, and 8 lepromatous). Seventy-three patients underwent US exam after completing treatment. Considering that abnormalities in at least one US measure reflect neuropathy, we observed similar frequencies of neuropathy between paucibacillary (PB) (35.7-57.1%) and multibacillary (MB) (50-65.1%) patients before treatment. The most frequently involved nerve in PB was common fibular, whereas in MB it was ulnar nerve. Before treatment, MB patients had higher CSA means for all examined nerves (p<0.05) and showed a weak tendency toward greater asymmetry (delta CSA, delta Utpt) compared to PB. Comparing patients with or without leprosy reactions (type 1, type 2 and/or neuritis), we observed greater thickening and asymmetry in the former group; moreover, we detected significant association between Doppler signal and reactions before treatment. After treatment, none of the evaluated risk factors was strongly related to worsening of sonographic findings; however, some analyzes suggested increased risk in MB patients (greater frequency of CSA abnormalities in MB, p>0.05) and in patients with previous leprosy reactions (odds ratio 4.67; 95% confidence interval 1.17-18.64; p<0.05 for CSA abnormalities at the median nerve). MB patients had higher frequencies of echogenicity abnormalities (p<0.05) after treatment and the groups with or without reactions had similar frequencies of echogenicity and Doppler abnormalities, without significant increment in odds ratio. Gender and duration of disease were not significant risk factors for progression of US abnormalities. Peripheral neuropathy demontrated by US is common in all types of leprosy, regardless of classification and presence of reactions. Sonographic abnormalities may not fully improve; they may even worsen despite treatment. As the stigma related to leprosy is due to the consequences of neuropathy, it is essential the improvement of diagnostic and therapeutic procedures focusing peripheral nerve involvement.

Currently there does not exist a type of peripheral nerve interface that adequately combines spatial selectivity, spatial coverage and low invasiveness. In order to address this lack, we investigated the application of bioelectric source localization algorithms, adapted from electroencephalography/magnetoencephalography, to recordings from a 56-contact “matrix” nerve cuff electrode. If successful, this strategy would enable us to improve current neuroprostheses and conduct more detailed investigations of neural control systems. Using forward field similarities, we first developed a method to reduce the number of unnecessary variables in the inverse problem, and in doing so obtained an upper bound on the spatial resolution. Next, a simulation study of the peripheral nerve source localization problem revealed that the method is unlikely to work unless noise is very low and a very accurate model of the nerve is available. Under more realistic conditions, the method had localization errors in the 140 μm-180 μm range, high numbers of spurious pathways, and low resolution. On the other hand, the simulations also showed that imposing physiologically meaningful constraints on the solution can reduce the number of spurious pathways. Both the influence of the constraints and the importance of the model accuracy were validated experimentally using recordings from rat sciatic nerves. Unfortunately, neither idealized models nor models based on nerve sample cross-sections were sufficiently accurate to allow reliable identification of the branches stimulated during the experiments. To overcome this problem, an experimental leadfield was constructed using training data, thereby eliminating the dependence on anatomical models. This new strategy was successful in identifying single-branch cases, but not multi-branches ones. Lastly, an examination of the information contained in the matrix cuff recordings was performed in comparison to a single-ring configuration of contacts. The matrix cuff was able to achieve better fascicle discrimination due to its ability to select among the most informative locations around the nerve. These findings suggest that nerve cuff-based neuroprosthetic applications would benefit from implanting devices with a large number of contacts, then performing a contact selection procedure. Conditions that must be met before source localization approaches can be applied in practice to peripheral nerves were also discussed.