Low-Intensity Photobiomodulation Decreases Neuropathic Pain in Paw Ischemia-Reperfusion and Spared Nervus Ischiadicus Injury Experimental Models.

BACKGROUND: There is a wide range of animal models available today for studying chronic pain associated with a variety of etiologies and an extensive list of clinical manifestations of peripheral neuropathies. Photobiomodulation is a new tool for the treatment of pain in a convenient, noninvasive way. OBJECTIVE: The aim of this work is to elucidate the effects of infrared light-emitting diodes (LEDs) on behavioral responses to nociceptive stimuli in chronic pain models. METHODS: Forty-eight Swiss male mice weighing 25 to 35 g were used. Two chronic pain models, ischemia-reperfusion (IR) and spared spinal nerve injury, were performed and then treated with infrared LED irradiation (390 mW, 890 nm, 17.3 mW/cm2 , 20.8 J/cm2 , for 20 minutes). The behavioral tests used were a mechanical hypersensitivity test von Frey test) and a cold allodynia test (acetone test). RESULTS: The results showed that, in the IR model, the infrared LED had a significant effect on mechanical stimulation and cold allodynia on every day of treatment. In the spared nerve injury model, an analgesic effect was observed on every treatment day (when started on the 3rd and 7th days after the surgery). In both models, the effect was abolished when the treatment was interrupted. CONCLUSIONS: These findings suggest that photobiomodulation therapy may be a useful adjunct treatment for chronic pain.

Radiotherapy for Melanoma with Perineural Invasion: University of Florida Experience.

PURPOSE: Outcomes after adjuvant radiotherapy for cutaneous melanoma with perineural invasion (PNI). METHODS: Seven patients (5 cutaneous, 2 recurrent nerve lesions) received radiotherapy. RESULTS: At a median 4.5 years: Two patients did not recur; no local failures occurred. Three patients who omitted nodal irradiation developed regional failures (2 out-of-field, 1 in-field). Three patients developed distant metastases. Four died with disease (median, 3.6 years); 1 died from intercurrent disease (13.0 years). Two are alive without disease (6.8 and 11.6 years). No patient experienced grade ≥3 toxicity. CONCLUSIONS: Postoperative radiotherapy can reduce local recurrences; primary radiotherapy for unresectable disease is recommended.

Inconsistency of a recently proposed method for assessing magnetic field exposure for protection against peripheral nerve stimulation in occupational situations.

A non-binding guide to practical implementation of European Directive 2013/35/EU concerning the limitation of occupational exposure against electromagnetic fields has been published recently. With regard to exposure assessment this guide proposes practically applicable assessment methods for non-uniform and non-sinusoidal environmental electric and magnetic fields, respectively. For non-sinusoidal magnetic fields in the low frequency range this guide proposes a time domain assessment (TDA) method, claimed to reduce the overestimation of exposure inherent to other assessment methods while being based on fundamental physiological principles regarding nerve stimulation. In the present paper we demonstrate that the proposed TDA method is not consistent with the obvious underlying principles of directive 2013/35/EU. Based on practically relevant waveforms and general considerations it can be shown that external magnetic fields may be deemed compliant by the TDA method although the underlying exposure limit values defined in 2013/35/EU may be exceeded. We therefore strongly recommend that the TDA method is removed from the guide for implementing 2013/35/EU as soon as possible.

Peripheral nerve stimulation-optimal gradient waveform design.

PURPOSE: Modern magnetic resonance imaging scanners with high-performance gradient systems have high maximum gradient strength (Gmax ) and slew rate (Smax ). Peripheral nerve stimulation (PNS) is often a more limiting factor for gradient waveform design than Gmax and Smax . Traditionally, the slew rate is derated globally to adhere to PNS limitations. METHODS: In this work, the PNS limitation is already included in the gradient waveform design in the form of a time-varying slew rate, hence shortening the overall gradient duration. RESULTS: Spiral and echo-planar imaging trajectories were designed with a multitude of parameters, and it was demonstrated that trajectory durations from conventional to PNS-optimal design can be shortened by 8 and 3%, respectively. CONCLUSION: Including PNS-limits in the gradient waveform design can shorten the duration of gradient trajectories, thereby reducing associated artifacts.

Noninvasive and painless magnetic stimulation of nerves improved brain motor function and mobility in a cerebral palsy case.

Motor deficits in cerebral palsy disturb functional independence. This study tested whether noninvasive and painless repetitive peripheral magnetic stimulation could improve motor function in a 7-year-old boy with spastic hemiparetic cerebral palsy. Stimulation was applied over different nerves of the lower limbs for 5 sessions. We measured the concurrent aftereffects of this intervention on ankle motor control, gait (walking velocity, stride length, cadence, cycle duration), and function of brain motor pathways. We observed a decrease of ankle plantar flexors resistance to stretch, an increase of active dorsiflexion range of movement, and improvements of corticospinal control of ankle dorsiflexors. Joint mobility changes were still present 15 days after the end of stimulation, when all gait parameters were also improved. Resistance to stretch was still lower than prestimulation values 45 days after the end of stimulation. This case illustrates the sustained effects of repetitive peripheral magnetic stimulation on brain plasticity, motor function, and gait. It suggests a potential impact for physical rehabilitation in cerebral palsy.

Radiation-induced changes in peripheral nerve by stereotactic radiosurgery: a study on the sciatic nerve of rabbit.

A large fractional dose in radiotherapy produces better radiobiological results, but there is always a concern of radiation-induced damage to the normal tissues, especially peripheral nerves. This study was to evaluate the radiation-induced changes of sciatic nerve treated by stereotactic radiosurgery (SRS) in rabbit. A localization test was performed on 3 rabbits to determine the reference landmarks to the location of the sciatic nerve of rabbit in CT. Another 12 rabbits were irradiated by a dose of 25 Gy at the sciatic nerve using SRS with 5 non-coplanar arcs. The rabbits were randomized into 3 groups and euthanised at 3, 5, and 7 months after radiotherapy, respectively. Apart from the sensory and motor tests performed on the rabbits, segments of the sciatic nerve were prepared for hematoxylin and eosin staining. Histologic and ultra-structural examinations including morphometric analyses were conducted and compared with the control (non-irradiated side). Apart from the loosening of myelin layers at 5 months, no prominent changes were shown at 3 and 5 months after irradiation. At 7 months, despite the fact that the sensation and motor function tests remained intact, ultra-structural examination showed obvious vacuolation, degeneration and necrosis of the axons with myelin fragmentation. In addition, morphometric analysis indicated that, when compared with the control, there was significant reduction in fiber diameter, increase of myelin thickness and decrease of G ratio (P < 0.01). Although it remained functionally intact, a focal single dose of 25 Gy caused significant microscopic damage to the rabbit sciatic nerve at 7 months after irradiation. Escalating doses with large single fractional dose involving peripheral nerves should be carried out with caution.

[Neurological complications of neurooncological therapy]. / Neurologische Komplikationen der neuroonkologischen Therapie.

Neurological complications of therapeutic procedures for brain tumors are increasingly being recognized. These encompass the classic types of central and peripheral neurotoxicity, such as radiotherapy-induced leukoencephalopathy and platinum-induced neuropathy. However, the advent of novel protocols and targeted therapeutics has expanded the spectrum of neurological complications. A problem of considerable importance is pseudoprogression after radiochemotherapy with temozolomide. Among the new targeted drugs complications of therapy with bevacizumab are the subject of intense discussion. In this review article the neurotoxic potential of intrathecal chemotherapy, kinase inhibitors, immunological strategies and local therapies are summarized. Knowledge about neurological complications of brain tumor therapy procedures is important for risk assessment and patient information.

Interneuronal activity in reflex pathways from group II muscle afferents is monitored by dorsal spinocerebellar tract neurons in the cat.

The main aim of the study was to investigate whether group II muscle afferents contribute to the inhibition of dorsal spinocerebellar tract (DSCT) neurons and thereby modulate information provided by these neurons in the cat. In intracellular recordings, we found disynaptic IPSPs from group II afferents in the majority of DSCT neurons, most often in parallel with IPSPs evoked from group I afferents. In an attempt to identify interneurons that mediate these IPSPs, the second aim of the study, laminas IV-VII in midlumbar segments were searched for interneurons antidromically activated by stimuli applied within Clarke's column. Such interneurons were found in regions in which focal field potentials were evoked by group I and II afferents, or ventral to them, and most were coexcited by these afferents. The input to these interneurons and their location indicate that they belonged to the previously identified population of premotor interneurons in disynaptic pathways between group I and II afferents and hindlimb motoneurons. The study leads thus to the conclusion that inhibitory actions of group II afferents on DSCT neurons are collateral to actions on motoneurons and that DSCT neurons monitor inhibitory actions of group II afferents on motoneurons as closely as they monitor actions of group I afferents. The results also indicate that interneurons mediating disynaptic reflex actions from tendon organ (group Ib) afferents and those mediating disynaptic actions from secondary muscle spindle (group II) afferents to motoneurons may be parts and parcel of the same interneuronal population rather than constitute distinct interneuronal populations.

Complete optical neurophysiology: toward optical stimulation and recording of neural tissue.

Direct optical methods to stimulate and record neural activity provide artifact-free, noninvasive, and noncontact neurophysiological procedures. For stimulation, focused mid-infrared light alters membrane potential and activates individual neural processes. Simultaneous intrinsic scattered light parameters, including birefringence changes, can record neural activity with signals similar to potentiometric dyes. The simultaneous combination of optical stimulation and optical recording techniques provide the potential for powerful tools that may someday remove the need for invasive wires during electrophysiological recordings.

Side effects of radiation in musculoskeletal oncology.

Radiation therapy is applied for systemic effects to patients with bone and soft tissue tumors and for local effects that facilitate the surgical procedure. However, while it remains an essential treatment of cancers, radiation therapy is associated with unwanted complications. The purpose of this review is to summarize information regarding the complications of radiation in musculoskeletal oncology and their management. Because preoperative radiotherapy is associated with an increased risk of wound complications and postoperative radiation is associated with an increased risk of postradiation fractures, the physician requires additional information in deciding on the best method of treatment, and such information is provided in this review.

Base of skull recurrences after treatment of salivary gland cancer with perineural invasion reduced by postoperative radiotherapy.

OBJECTIVES: To determine the effect of postoperative radiation therapy for salivary gland carcinomas in the presence of microscopic perineural invasion. DESIGN AND SETTING: Retrospective review at an academic tertiary center. PARTICIPANTS: One hundred and forty patients with pathological evidence of perineural invasion at the time of initial surgery for salivary gland carcinomas were analysed. Sixteen patients (11%) had major (named) nerve involvement. Ninety-four patients (67%) received postoperative radiation therapy to the primary site, and the portal films of 65 of these patients were available for review. MAIN OUTCOME MEASURES: The incidence of skull base recurrences among patients treated by surgery with or without postoperative radiation therapy. RESULTS: Ten patients experienced skull base recurrences. T4 disease and the omission of postoperative radiation therapy were identified as significant predictors of skull base recurrence. Postoperative radiation therapy reduced the actuarial probability of skull base recurrence from 15% to 5% (P = 0.03). The crude rates of skull base recurrence were 6% (2/35) and 10% (3/30), respectively, for patients whose skull base were and were not confirmed to be encompassed in the irradiation field. The 5-year overall survival for patients who experienced a skull base recurrence was 19% compared to 91% for those who did not (P < 0.001). CONCLUSION: The use of postoperative radiation therapy significantly reduced the incidence of skull base recurrence among salivary gland carcinoma patients with perineural invasion.

Glutamate-mediated spinal reflex potentiation involves ERK 1/2 phosphorylation in anesthetized rats.

The extracellular signal-regulated kinase (ERK) cascades are suggested to contribute to excitatory plasticity in the CNS, including the spinal cord. This study investigated whether the ERK involves in the repetitive stimulation-induced spinal reflex potentiation (SRP) in the pelvic nerve-to-external urethra sphincter reflex activities. External urethra sphincter electromyogram in response to pelvic afferent nerve test stimulation (TS, 1/30 Hz) or repetitive stimulation (RS, 1 Hz) was recorded in anesthetized rats. TS evoked a baseline reflex activity, whereas RS produced SRP in associated with significant ERK 1/2 phosphorylation. RS-induced SRP and ERK 1/2 phosphorylation were both abolished by pretreatment of U0126 (MEK inhibitor). Intrathecal CNQX (AMPA receptor antagonist) attenuated, while AP5 (NMDA receptor antagonist) abolished the RS-induced SRP and ERK 1/2 phosphorylation. Pretreated U0126 abolished the SRP elicited by glutamatergic agonists including glutamate, NMDA and AMPA. Intrathecal H89 and BIS7 (PKA and PKC inhibitors, respectively) both abolished the RS- and glutamate agonist-induced SRP as well as ERK 1/2 phosphorylation. In addition, forskolin and PMA (PKA and PKC activator, respectively) induced SRP, which were both abolished by pretreated U0126. Saline distension, mimicking the storage phase of the urinary bladder, induced SRP and ERK 1/2 phosphorylation. In conclusion, activated ERK 1/2 may produce SRP in the pelvic nerve-to-external urethra sphincter reflex activity, which is essential for urine continence. In addition, blockage of spinal ERK 1/2 activation decreases the physiological function of the urethra, indicating that phosphorylation of the ERK 1/2 cascade may represent a novel target for the treatment of patients with neurological incontinence of spinal origin.

N-methyl-D-aspartate mechanisms in depolarization of augmenting expiratory neurons during the expulsive phase of fictive cough in decerebrate cats.

Cough reflex is characterized by a large expulsive phase for expelling the mucus or particles from the airway. The present study investigated the involvement of N-methyl-D-aspartate (NMDA) mechanisms in the expulsive phase of cough reflex using decerebrate and paralyzed cats. A fictive cough was induced by repetitive stimulation of the superior laryngeal nerve, which was characterized by an increased inspiratory discharge in the phrenic nerve (the stage 1 of fictive cough; SC1) and large spindle-shaped discharge in the iliohypogastric nerve (the stage 2 of fictive cough; SC2). Intravenous injection of an antagonist of NMDA receptors, dizocilpine (0.1mg/kg), increased the threshold intensity of stimulation for inducing a fictive cough. The SC2 iliohypogastric response was more vulnerable to dizocilpine than the SC1 phrenic response. Membrane potential of augmenting expiratory (aug-E) neurons was recorded from the caudal ventral respiratory group. Aug-E neurons showed a large depolarization with a high frequency discharge during the SC2 in major cases (n=35) and hyperpolarization in minor cases (n=6). Dizocilpine inhibited the occurrence of these SC2 responses of aug-E neurons without any effect on the basal respiratory fluctuations of membrane potential. This drug had no significant effect on waves of excitatory and inhibitory postsynaptic potentials evoked in aug-E neurons by single pulse stimulation of the SLN. The present results demonstrated that NMDA mechanisms contribute preferentially to the expulsive phase response in aug-E neurons during fictive cough reflex.

Limb temperature and nerve conduction velocity during warming with hot water blankets.

Electrodiagnostic assessments of the peripheral nervous system often require limb warming. The traditional warming method, the hot water bath, has several disadvantages. We present an alternative: hot water blankets containing circulating water of a constant temperature. In addition to having practical advantages, these blankets allow for accurate and continuous monitoring of limb temperature and nerve conduction velocity (NCV) during warming. We therefore aimed to determine (1) the temperature dependence of the NCV of the median motor and sensory nerve, deep peroneal nerve, and sural nerve during warming with blankets, and (2) the optimal warming strategy for clinical purposes. We warmed the limbs of 10 subjects for 90 minutes with blankets set at a temperature of 41 degrees C. During warming, the NCV of the three nerves and distal motor latency of the two motor nerves were measured every 2(1/2) minutes. After 25 minutes of warming from an initial temperature of 28 degrees C, the NCV and distal motor latency of all nerves were within the normal range. However, after median nerve warming until a predefined temperature of 34 degrees C (i.e., for 17 minutes on average), two of nine subjects showed abnormal NCVs. We therefore conclude that for limb warming with hot water blankets, a fixed 25-minute warming period is optimal.

Walking performance, medical outcomes and patient training in FES of innervated muscles for ambulation by thoracic-level complete paraplegics.

OBJECTIVE: To discuss functional electric stimulation (FES) gait training of upper motoneuron spinal cord injured complete paraplegics considering ambulation performance, physiologic and metabolic responses as well as psychologic outcome, while providing myologic insight into ambulation via FES when training starts many years post-injury. METHODS: Transcutaneous FES using the Parastep stimulation system, gait training methods with and without major emphasis on muscle reinforcement, cardiovascular and respiratory conditioning. Examination of myofiber tissues and correlation of normal muscles histology versus innervated muscles of upper motor neuron and of denervated muscles of lower motor neuron paraplegics. RESULTS: Published works in literature reviewed in this paper report average walking distance of 440 m/walk when major muscle reinforcement and preconditioning cardiovascular and respiratory systems precedes gait training, versus average 115 m/walk when undergoing direct gait training. Medical, metabolic and psychologic outcomes, as reported in several works, point to benefits of FES walking, including 60% increase in blood flow to lower extremities. Myofiber tissues of patients with upper motor neuron paralysis compare well with those of normal tissue even many years post-injury, while adipose tissue substitute muscle fibers in patients with lower motor neuron lesions. DISCUSSION: Transcutaneous FES allows considerably longer walking distances and speed at the end of training when training involves an extensive pre-conditioning program than with direct gait training. Medical and psychologic benefits are observed, especially concerning blood flow to the lower extremities. Myofiber examinations provide myologic understanding of effectiveness of FES many years post-injury.

Simulation studies of ultrashort, high-intensity electric pulse induced action potential block in whole-animal nerves.

A theoretical study of possible neuromuscular incapacitation based on the application of high-intensity, ultrashort electric pulses is presented. The analysis is applied to a rat, but the approach is general and can be extended to any whole-animal and applies for any arbitrary pulse waveform. It is hypothesized that repeatable and reversible action potential blocks in nerves can be attained based on the electroporation mechanism. Our numerical studies are based on the Hodgkin-Huxley distributed circuit representation of nerves, and incorporate a nodal analysis for the time-dependent and volumetric perturbing potentials and internal electric fields in whole animals. The predictions are compared to actual 600-ns experimental reports on rats and shown to be in very good agreement. Effective strength-duration plots for neuromuscular incapacitation are also generated.

Pulsed radiofrequency applied to the suprascapular nerve in painful cuff tear arthropathy.

The purpose of this study was to assess the efficacy of pulsed radiofrequency (PRF) applied to the suprascapular nerve for pain relief in medically unfit patients with painful cuff tear arthropathy. Twelve patients with chronic shoulder pain due to cuff tear arthropathy were recruited. The mean age was 68 years (range, 60-83 years). The suprascapular nerve was targeted at the suprascapular notch with PRF. The patients were assessed with the Oxford score, Constant score, and visual analog scale (VAS) pain score before ablation and 3 and 6 months after ablation. Statistical analysis was undertaken by use of the Friedman test. Ten patients showed improvement in the VAS score (P = .24) and Constant score (P = .005) and eleven in the Oxford score (P = .001). There was a deterioration in the VAS scores between 3 and 6 months, suggesting that the benefits were starting to wear off with time (P > .05). We conclude that PRF may be a useful therapeutic adjunct in patients with painful, end-stage rotator cuff tear arthropathy who are medically unfit for surgery.

Anti-inflammatory effects of electronic signal treatment.

Inflammation often plays a key role in the perpetuation of pain. Chronic inflammatory conditions (e.g. osteoarthritis, immune system dysfunction, micro-circulatory disease, painful neuritis, and even heart disease) have increased as baby boomers age. Medicine's current anti-inflammatory choices are NSAIDs and steroids; the value in promoting cure and side effect risks of these medications are unclear and controversial, especially considering individual patient variations. Electricity has continuously been a powerful tool in medicine for thousands of years. All medical professionals are, to some degree, aware of electrotherapy; those who directly use electricity for treatment know of its anti-inflammatory effects. Electronic signal treatment (EST), as an extension of presently available technology, may reasonably have even more anti-inflammatory effects. EST is a digitally produced alternating current sinusoidal electronic signal with associated harmonics to produce theoretically reasonable and/or scientifically documented physiological effects when applied to the human body. These signals are produced by advanced electronics not possible even 10 to 15 years ago. The potential long-lasting anti-inflammatory effects of some electrical currents are based on basic physical and biochemical facts listed in the text below, namely that of stimulating and signaling effective and long-lasting anti-inflammatory effects in nerve and muscle cells. The safety of electrotherapeutic treatments in general and EST in particular has been established through extensive clinical use. The principles of physics have been largely de-emphasized in modern medicine in favor of chemistry. These electrical treatments, a familiar application of physics, thus represent powerful and appropriate elements of physicians' pain care armamentaria in the clinic and possibly for prescription for use at home to improve overall patient care and maintenance of quality of life via low-risk and potentially curative treatments.

On the therapeutic viability of peripheral nerve stimulation for ilioinguinal neuralgia: putative mechanisms and possible utility.

Injury to the ilioinguinal nerve commonly follows during lower abdominal and pelvic surgery, especially with inguinal hernia repair, appendectomy, and hysterectomy. Other potential causes include low abdominal blunt trauma, iliac crest bone graft, psoas abscess, Pott's disease, and prolonged wearing of abdominally constrictive clothing. The actual incidence of ilioinguinal neuralgia is uncertain, as reported percentage ranges between 12% and 62%. Prompt and accurate diagnosis is critical, and appropriate treatments range from conservative pharmacologic management with nonopioid (eg, gabapentin, topiramate) as well as opioid agents, to surgical neurectomy of the proximal portion of the ilioinguinal nerve. Pharmacological treatment is frequently unsuccessful (particularly if delayed) and while surgery is successful in approximately 73% of cases, it can result in problematic paresthesias, and pain may continue to persist in some patients. Thus, minimally invasive techniques, such as peripheral nerve stimulation, may be viable in those patients who are refractory to pharmacological management, as an option to surgery, and who have not gained satisfactory pain relief through surgical intervention. We present three cases of successful pain control of ilioinguinal neuralgia with peripheral nerve stimulation. These cases demonstrate the potential benefits of neurostimulation including durable effective pain relief and decreased use of medication. Putative mechanisms of effect(s) and caveats for continued research to inform prudent employment of this technique are presented.

Peripheral neurostimulation in supraorbital neuralgia refractory to conventional therapy.

Supraorbital neuralgia has been identified as an infrequent cause of headache that may prove very difficult to control pharmacologically. Peripheral nerve stimulation using electrodes to stimulate the nerve segmentally responsible for the zone of pain may constitute a management alternative in such cases. We present the case of a patient with headache because of posttraumatic supraorbital neuralgia, refractory to medical treatment, with good analgesic control after peripheral nerve stimulation. Peripheral nerve stimulation may be considered a safe, reversible treatment for patients with headache secondary to supraorbital neuralgia who respond poorly to pharmacological treatment, thus avoiding irreversible alternatives such as surgery.