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Introduction: Current oral treatments for pain in diabetic peripheral neuropathy (DPN) do not affect the progression of DPN i.e., "disease modification." We assessed whether Capsaicin 8% patch treatment can provide pain relief and also restore nerve density and function via nerve regeneration, in both painful (PDPN) and non-painful (NPDPN) diabetic peripheral neuropathy. Methods: 50 participants with PDPN were randomized to receive Capsaicin 8% patch Qutenza with Standard of Care (SOC) (PDPN Q+SOC group), or SOC alone (PDPN SOC group). Pain symptoms were assessed with a diary (Numerical Pain Rating Scale, NRPS) and questionnaires. Investigations included quantitative sensory testing (QST) and distal calf skin biopsies, at baseline and 3 months after baseline visit; subsequent options were 3-monthly visits over 1 year. 25 participants with NPDPN had tests at baseline, and 3 months after all received Capsaicin 8% patch treatment. Results: At 3 months after baseline, PDPN Q+SOC group had reduction in NPRS score (p = 0.0001), but not PDPN SOC group. Short-Form McGill Pain Questionnaire (SF-MPQ) showed significant reductions in scores for overall and other pain descriptors only in the PDPN Q+SOC group. Warm perception thresholds were significantly improved only in the PDPN Q+SOC group (p = 0.02), and correlated with reduction in SF-MPQ overall pain score (p = 0.04). NPDPN Q+SOC group did not report pain during the entire study. Density of intra-epidermal nerve fibers (IENF) with PGP9.5 was increased at 3 months in PDPN Q+SOC (p = 0.0002) and NPDPN Q+SOC (p = 0.002) groups, but not in the PDPN SOC group. Increased sub-epidermal nerve fibers (SENF) were observed with GAP43 (marker of regenerating nerve fibers) only in PDPN Q+SOC (p = 0.003) and NPDPN Q+SOC (p = 0.0005) groups. Pain relief in the PDPN Q+SOC group was correlated with the increased PGP9.5 IENF (p = 0.0008) and GAP43 (p = 0.004), whereas those with lack of pain relief showed no such increase; in some subjects pain relief and increased nerve fibers persisted over months. PGP9.5 IENF increase correlated with axon-reflex vasodilatation in a NPDPN Q+SOC subset (p = 0.006). Conclusions: Capsaicin 8% patch can provide pain relief via nerve regeneration and restoration of function in DPN (disease modification). It may thereby potentially prevent diabetic foot complications, including ulcers.
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Introduction: Neuropathic pain associated with Non-freezing Cold Injury (NFCI) is a major burden to military service personnel. A key feature of NFCI is reduction of the intra-epidermal nerve fibre density in skin biopsies, in keeping with painful neuropathy. Current oral treatments are generally ineffective and have undesirable side effects. Capsaicin 8% patch (Qutenza) has been shown to be well-tolerated and effective for reducing neuropathic pain, for up to 3 months after a single 30-minute application. Methods: In this single-centre open label study, 16 military participants with NFCI (mean duration 49 months) received 30-minute Capsaicin 8% patch treatment to the feet and distal calf. Pain symptoms were assessed using a pain diary (with the 11-point Numerical Pain Rating Scale, NPRS) and questionnaires, the investigations included skin biopsies, performed before and three months after treatment. Results: Participants showed significant decrease in spontaneous pain (mean NPRS: -1.1, 95% CI: 0.37 to 1.90; p = 0.006), and cold-evoked pain (-1.2, 95% CI: 0.40 to 2.04; p = 0.006). The time-course of pain relief over 3 months was similar to other painful neuropathies. Patient Global Impression of Change showed improvement (p = 0.0001). Skin punch biopsies performed 3 months after the patch application showed significant increase of nerve fibres with structural marker PGP9.5 (intra-epidermal nerve fibres [IENFs], p < 0.0001; sub-epidermal nerve fibres [SENFs]; p =< 0.0001), and of regenerating nerve fibres with their selective marker GAP43 (p = 0.0001). The increase of IENFs correlated with reduction of spontaneous (p = 0.027) and cold-evoked pain (p = 0.019). Conclusions: Capsaicin 8% patch provides an exciting new prospect for treatment of NFCI, with regeneration and restoration of nerve fibres, for the first time, in addition to pain relief.
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BACKGROUND: The Contact Heat Evoked Potential Stimulator (CHEPS) rapidly stimulates cutaneous small nerve fibres, and resulting evoked potentials can be recorded from the scalp. We have studied patients with symptoms of sensory neuropathy and controls using CHEPS, and validated the findings using other objective measures of small nerve fibres i.e. the histamine-induced skin flare response and intra-epidermal fibres (IEF), and also quantitative sensory testing (QST), a subjective measure. METHODS: In patients with symptoms of sensory neuropathy (n = 41) and healthy controls (n = 9) we performed clinical examination, QST (monofilament, vibration and thermal perception thresholds), nerve conduction studies, histamine-induced skin flares and CHEPS. Skin punch biopsies were immunostained using standard ABC immunoperoxidase for the nerve marker PGP 9.5 or the heat and capsaicin receptor TRPV1. Immunoreactive IEF were counted per length of tissue section and epidermal thickness recorded. RESULTS: Amplitudes of Adelta evoked potentials (muV) following face, arm or leg stimulation were reduced in patients (e.g. for the leg: mean +/- SEM - controls 11.7 +/- 1.95, patients 3.63 +/- 0.85, p = 0.0032). Patients showed reduced leg skin flare responses, which correlated with Adelta amplitudes (rs = 0.40, p = 0.010). In patient leg skin biopsies, PGP 9.5- and TRPV1-immunoreactive IEF were reduced and correlated with Adelta amplitudes (PGP 9.5, rs = 0.51, p = 0.0006; TRPV1, rs = 0.48, p = 0.0012). CONCLUSION: CHEPS appears a sensitive measure, with abnormalities observed in some symptomatic patients who did not have significant IEF loss and/or QST abnormalities. Some of the latter patients may have early small fibre dysfunction or ion channelopathy. CHEPS provides a clinically practical, non-invasive and objective measure, and can be a useful additional tool for the assessment of sensory small fibre neuropathy. Although further evaluation is required, the technique shows potential clinical utility to differentiate neuropathy from other chronic pain states, and provide a biomarker for analgesic development.
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Potenciais Somatossensoriais Evocados/fisiologia , Fibras Nervosas/fisiologia , Doenças do Sistema Nervoso Periférico/patologia , Limiar Sensorial/fisiologia , Pele/inervação , Adulto , Idoso , Biópsia/métodos , Eletroencefalografia/métodos , Feminino , Histamina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/efeitos da radiação , Doenças do Sistema Nervoso Periférico/fisiopatologia , Tempo de Reação/fisiologia , Limiar Sensorial/efeitos dos fármacos , Pele/fisiopatologia , Estatísticas não Paramétricas , Canais de Cátion TRPV/metabolismo , Ubiquitina Tiolesterase/metabolismoRESUMO
Motor but not sensory function has been described after spinal cord surgery in patients with brachial plexus avulsion injury. In the featured case, motor-related nerve roots as well as sensory spinal nerves distal to the dorsal root ganglion were reconnected to neurons in the ventral and dorsal horns of the spinal cord by implanting nerve grafts. Peripheral and sensory functions were assessed 10 years after an accident and subsequent spinal cord surgery. The biceps stretch reflex could be elicited, and electrophysiological testing demonstrated a Hoffman reflex, or Hreflex, in the biceps muscle when the musculocutaneous nerve was stimulated. Functional MR imaging demonstrated sensory motor cortex activities on active as well as passive elbow flexion. Quantitative sensory testing and contact heat evoked potential stimulation did not detect any cutaneous sensory function, however. To the best of the authors' knowledge, this case represents the first time that spinal cord surgery could restore not only motor function but also proprioception completing a spinal reflex arch.
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Neuropatias do Plexo Braquial/cirurgia , Plexo Braquial/lesões , Radiculopatia/cirurgia , Recuperação de Função Fisiológica/fisiologia , Reflexo/fisiologia , Raízes Nervosas Espinhais/lesões , Adulto , Vias Aferentes/lesões , Vias Aferentes/fisiologia , Vias Aferentes/cirurgia , Neuropatias do Plexo Braquial/fisiopatologia , Vias Eferentes/lesões , Vias Eferentes/fisiologia , Vias Eferentes/cirurgia , Seguimentos , Humanos , Masculino , Radiculopatia/fisiopatologia , Medula Espinal/fisiologia , Medula Espinal/cirurgia , Raízes Nervosas Espinhais/fisiopatologia , Raízes Nervosas Espinhais/cirurgiaRESUMO
The treatment of obstetric brachial plexus palsy (OBPP) with neuroma-in-continuity is controversial. The recent literature advocates excision of neuroma-in-continuity in OBPP and repair with nerve graft irrespective of its neurophysiological conductivity. This approach risks sacrificing the regenerating axons, and the result has not yet been proven to be superior to neurolysis alone. In this case report, the authors aim to outline their strategy of using the combination of preoperative and intraoperative clinical and neurophysiological findings to aid their decision making. The lack of upper trunk recovery and the unfavorable preoperative neurophysiological findings in a child with Narakas Group 4 OBPP at 5 months of age prompted an urgent exploration with the intention of performing neurotization. This procedure was abandoned and neurolysis was performed due to the favorable intraoperative neurophysiological findings. At 4 years of age, the child scored 12 of 15 on Mallet classification and has an excellent range of movement. No secondary operation was needed. The authors hope to highlight the idea that the surgical option for neurolysis alone should be kept open and that intraoperative electromyography can be a valuable tool to add to the surgeon's armamentarium.
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Neuropatias do Plexo Braquial/cirurgia , Eletromiografia , Monitorização Intraoperatória/métodos , Paralisia Obstétrica/cirurgia , Cuidados Pré-Operatórios , Pré-Escolar , Potenciais Somatossensoriais Evocados , Humanos , Lactente , Masculino , Recuperação de Função FisiológicaRESUMO
The efficacy of botulinum toxin (BTX) without systemic effects has led to the rapid development of applications in neuromuscular disorders, hyperactivity of sudomotor cholinergic-mediated glandular function, and pain syndromes. The successful use of BTX in conditions with muscle overactivity, such as dystonia and spasticity, has been established and new areas in the field of movement disorders such as tics, tremor, myoclonic jerks, and stuttering has been explored with satisfactory results. Strategies to temporarily inactivate muscle function after orthopaedic or neurosurgery have also been developed. BTX treatment of hyperhidrosis was followed by its application in other hypersecretory conditions (hyperlacrimation and nasal hypersecretion) and in excessive drooling. Studies are in progress, aimed at optimising the technique and protocol of administration. Other applications for BTX have been proposed in gastroenterological and urogenital practice; it appears to be effective in replacing standard surgical procedures. Trials of BTX in painful conditions are ongoing mainly on refractory tension headache, migraine, and backache as well as dystonia-complex regional pain syndrome and myofascial pain with promising results. Recently, the fastest growing use for BTX toxin has been in the cosmetic applications. Clearly, the indications for the use of BTX are expanding, but further clinical trials will be needed in many different areas.
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Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Dor/tratamento farmacológico , Sialorreia/tratamento farmacológico , Antidiscinéticos/farmacologia , Toxinas Botulínicas/farmacologia , Vias de Administração de Medicamentos , Distonia/tratamento farmacológico , Humanos , Glândula Parótida/efeitos dos fármacos , Cirurgia Plástica , Tremor/tratamento farmacológicoRESUMO
We investigated the extent to which oscillatory drives to muscle, believed to arise mainly from the motor cortex, are exaggerated and/or fail to react normally to peripheral stimulation in writer's cramp. We used the coherence between active forearm flexor and intrinsic hand muscles as our index of such drives before and after digital nerve stimulation of the dominant hand. The results in 8 patients with writer's cramp were compared with those in eight age- and sex-matched healthy subjects. We found no significant difference in either the strength of intermuscular coherence or its modulation by cutaneous stimulation between patients and healthy subjects during voluntary flexion of the wrist and extension-abduction of the fingers. Therefore, we were unable to provide evidence for a pervasive disturbance of oscillatory cortical motor outflow in writer's cramp.