Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study we evaluated the effect... more
Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study we evaluated the effect of affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated which received GDNF or nerve growth factor (NGF) with the delivery system within the conduit, control groups excluding one or more components of the delivery system, and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry and electron microscopy. The use of the delivery system (DS) with either GDNF or NGF resulted in a higher frequency of nerve regeneration vs. control groups, as evidenced by a neural structure spanning the 13 mm gap. The GDNF DS and NGF DS groups were also similar to the nerve isograft group in measures of nerve fiber density, percent neural tissue and myelinated area measurements, but not in terms of total fiber counts. In addition, both groups contained a significantly greater percentage of larger diameter fibers, with GDNF DS having the largest in comparison to all groups, suggesting more mature neural content. The delivery of GDNF via the affinity-based delivery system can enhance peripheral nerve regeneration through a silicone conduit across a critical nerve gap and offers insight into potential future alternatives to the treatment of peripheral nerve injuries.
This study was undertaken to investigate any relationship between sensory features and neck pain in female office workers using quantitative sensory measures to better understand neck pain in this group. Office workers who used a visual... more
This study was undertaken to investigate any relationship between sensory features and neck pain in female office workers using quantitative sensory measures to better understand neck pain in this group. Office workers who used a visual display monitor for more than four hours per day with varying levels of neck pain and disability were eligible for inclusion. There were 85 participants categorized according to their scores on the neck disability index (NDI): 33 with no pain (NDI < 8); 38 with mild levels of pain and disability (NDI 9–29); 14 with moderate levels of pain (NDI ⩾ 30). A fourth group of women without neck pain (n = 22) who did not work formed the control group. Measures included: thermal pain thresholds over the posterior cervical spine; pressure pain thresholds over the posterior neck, trapezius, levator scapulae and tibialis anterior muscles, and the median nerve trunk; sensitivity to vibrotactile stimulus over areas of the hand innervated by the median, ulnar and radial nerves; sympathetic vasoconstrictor response. All tests were conducted bilaterally. ANCOVA models were used to determine group differences between the means for each sensory measure. Office workers with greater self-reported neck pain demonstrated hyperalgesia to thermal stimuli over the neck, hyperalgesia to pressure stimulation over several sites tested; hypoaesthesia to vibration stimulation but no changes in the sympathetic vasoconstrictor response. There is evidence of multiple peripheral nerve dysfunction with widespread sensitivity most likely due to altered central nociceptive processing initiated and sustained by nociceptive input from the periphery.
Peripheral nerve stimulation and, recently, peripheral nerve field stimulation are excellent options for the control of extremity pain in instances where conventional methods have failed and surgical treatment is ruled inappropriate. New... more
Peripheral nerve stimulation and, recently, peripheral nerve field stimulation are excellent options for the control of extremity pain in instances where conventional methods have failed and surgical treatment is ruled inappropriate. New techniques, ultrasound guidance, smaller generators, and task-specific neuromodulatory hardware and leads result in increasingly safe, stable and efficacious treatment of pain in the extremities. Peripheral nerve stimulation has shown to be an increasingly viable option for many painful conditions with neuropathic and possibly nociceptive origins. This chapter focuses on the historical use of neuromodulation in the extremities, technical tasks associated with implant, selection of candidates, and potential pitfalls of and solutions for implanting devices around the peripheral nervous system for extremity pain.
Botulinum neurotoxins induce a prolonged muscle paralysis by specifically blocking the release of neuronal transmitters from peripheral nerve junctions. Potency testing of toxin and antitoxin therapies is entirely dependent on mouse... more
Botulinum neurotoxins induce a prolonged muscle paralysis by specifically blocking the release of neuronal transmitters from peripheral nerve junctions. Potency testing of toxin and antitoxin therapies is entirely dependent on mouse lethality bioassay which is associated with extreme suffering of large numbers of animals to ensure high precision. The mouse phrenic nerve-diaphragm assay is an ex vivo assay that closely mimics in vivo respiratory paralysis offering substantial refinement and reduction in the number of animals used. A range of botulinum antitoxin standards, one licenced product and experimental antitoxins were tested for neutralising potency using ex vivo hemidiaphragm assay and compared with in vivo determined activities. Overall, there was an excellent agreement between neutralising activity detected by the two assay systems and for each toxin serotype using only 4–7 replicates for each product (almost perfect concordance for type A antitoxins: ρ = 0.997, and substantial concordance for type B antitoxins: ρ = 0.991 and type E antitoxins: ρ = 0.964, respectively). These findings confirm that the mouse nerve-diaphragm preparation can provide a functional ex vivo replacement assay for specific, sensitive and precise assessment of toxin and antitoxin activity.
A 37-year-old women presented with a 15-year history of slowly progressive atrophy and weakness in the right lower extremity. She also complained of mild pain and paresthesia over the dorsum of the right foot. The electrophysiological... more
A 37-year-old women presented with a 15-year history of slowly progressive atrophy and weakness in the right lower extremity. She also complained of mild pain and paresthesia over the dorsum of the right foot. The electrophysiological study revealed chronic axonal damage in the right sciatic nerve. The magnetic resonance imaging of the right thigh and lumbosacral plexus disclosed a right sciatic nerve fusiform mass and enlarged lumbosacral roots. The patient underwent a right sural nerve biopsy and the pathological investigation demonstrated onion bulb-shaped whorls consistent with the appearance of intraneural perineurioma, a focal hypertrophic peripheral nerve tumor, WHO grade I. Rare cases may be due to loss of ARSA at 22q13. According to the literature, these tumours are static or slowly progressive, remain confined to their original distribution and have low morbidity. Because of the intensive evaluation needed for diagnosis, this condition is probably under-recognized.
A thorough physical examination begins with a detailed history followed by inspection, palpation, and testing of muscle strength, tone, reflexes, and sensation. This systematic approach to the physical examination is useful for the... more
A thorough physical examination begins with a detailed history followed by inspection, palpation, and testing of muscle strength, tone, reflexes, and sensation. This systematic approach to the physical examination is useful for the peripheral nervous system and vascular system so pertinent details are not missed. When inspecting neurovascular structures, the physical examination is the primary initial clinical assessment. In addition to these fundamental aspects of the physical examination, many “special” provocation or relief tests and signs have been developed. The clinician then forms an impression from the information gathered during the history and physical examination and may use more advanced diagnostic tests to rule in or rule out a diagnosis.
Injury in the lower limbs is extremely frequent in most sport activities, particularly when prolonged running and physical contact are prominent features. A major challenge is the differential diagnosis between muscle, joint and nerve... more
Injury in the lower limbs is extremely frequent in most sport activities, particularly when prolonged running and physical contact are prominent features. A major challenge is the differential diagnosis between muscle, joint and nerve lesions, although it should always be considered that combined lesions are quite frequent. In this part of the review, the most frequent nerve entrapment and traumatic
