Diabetic distal symmetric polyneuropathy: effect of low-intensity laser therapy.

Low-intensity laser therapy (LILT) has been considered as a treatment modality in diabetic distal symmetric polyneuropathy (DSP). The aim of this study is to determine the effectiveness of LILT on DSP. We examined 107 subjects with type 2 diabetes for detection of DSP using the Michigan Neuropathy Screening Instrument (MNSI). Seventeen subjects were eligible to be enrolled in the study. Nerve conduction studies (NCS) were performed in all eligible subjects as an objective method to confirm neuropathy. The participants received LILT three times a week for ten sessions. NCSs were reevaluated after completion of the treatment. The absolute changes in NCS parameters were considered to establish the effectiveness of the treatment. Baseline demographics were similar in all participants. The mean differences of NCV parameters were considered for comparison. At the end of the study, the subjects showed a significant increase in neural potential amplitudes (p < 0.05). This study clearly demonstrated a significant positive effect of LILT on improvement of nerve conduction velocity on diabetic distal symmetric polyneuropathy (DSP). This finding supports the therapeutic potential of LILT in DSP.

Millimeter wave effects on electrical responses of the sural nerve in vivo.

Millimeter wave (MMW, 42.25 GHz)-induced changes in electrical activity of the murine sural nerve were studied in vivo using external electrode recordings. MMW were applied to the receptive field of the sural nerve in the hind paw. We found two types of responses of the sural nerve to MMW exposure. First, MMW exposure at the incident power density >/=45 mW/cm(2) inhibited the spontaneous electrical activity. Exposure with lower intensities (10-30 mW/cm(2)) produced no detectable changes in the firing rate. Second, the nerve responded to the cessation of MMW exposure with a transient increase in the firing rate. The effect lasted 20-40 s. The threshold intensity for this effect was 160 mW/cm(2). Radiant heat exposure reproduced only the inhibitory effect of MMW but not the transient excitatory response. Depletion of mast cells by compound 48/80 eliminated the transient response of the nerve. It was suggested that the cold sensitive fibers were responsible for the inhibitory effect of MMW and radiant heat exposures. However, the receptors and mechanisms involved in inducing the transient response to MMW exposure are not clear. The hypothesis of mast cell involvement was discussed.

Taxometric analysis of biceps femoris EMG following electrocutaneous stimulation over the sural nerve: determining the latent structure of the nociceptive flexion reflex (NFR).

The nociceptive flexion reflex (NFR) is a polysynaptic withdrawal reflex typically assessed from biceps femoris electromyogram (EMG) following noxious stimulation of the ipsilateral sural nerve. Electrophysiological evidence suggests the reflex is elicited following the activation of small diameter A-delta afferents. As a result, the NFR is assumed to be a categorically distinct construct that emerges from EMG activity only following nociceptor activation. Despite the widespread use of the NFR in pain research, there has been little attempt to verify the latent structure of the NFR. The present study used "coherent cut kinetics" taxometric analyses to examine whether the latent structure of biceps femoris EMG reflects the taxonic structure that would be predicted from electrophysiological evidence. To achieve this end, preliminary analyses first compared different methods of scoring NFR magnitude. Results suggested the presence of a taxon in the covariance of biceps femoris EMG and stimulus intensity that is likely to be the NFR. Furthermore, preliminary analyses suggested the best method of scoring NFR magnitude was using Cohen's d. Implications of these results are discussed.

Acute pain increases heart rate: differential mechanisms during rest and mental stress.

The main aim was to investigate if acutely stressed subjects have abnormal heart rate variability responses to acute pain. Efferent cardiac autonomic activity was assessed by analyzing RR interval variation in 26 male volunteers. Heart rate variability was measured as mean and standard deviation of normal RR intervals (mean RR, SDNN) and by power spectral analysis where high frequency (HF) and low frequency (LF) power were used as indexes of vagal function and of sympatho-vagal interaction, respectively. Coefficient of component variance in the LF and HF bands (CCV-LF, CCV-HF) was estimated to adjust for possible influences of different mean RR levels on power amplitude. Subjects received painful and non-painful sural nerve stimulations during rest, during attention to pain, and during mental stress. Our results show that pain significantly decreased mean RR and increased LF power and CCV-LF during rest and during attention to pain. SDNN, HF power, and total power were not affected by pain. During mental stress, pain significantly decreased mean RR but failed to affect other heart rate variability parameters. We conclude that acute pain induced efferent cardiac sympathetic activation during rest and during attention to pain as LF power and CCV-LF increased without alterations of pure vagal heart rate variability measures. During mental stress, pain inhibited mean RR without changing heart rate variability measures suggesting that pain does not increase efferent cardiac sympathetic activity during mental stress. Pain induced decrease of mean RR during mental stress may be caused by the release of catecholamines into the systemic circulation.

A C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic and heterotopic acupoints in rats selectively destructive effects on myelinated and unmyelinated afferent fibers.

The aims of this study were to explore the C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic or heterotopic acupoints, and to determine the influence selectively destroyed myelinated and unmyelinated afferent fibers on the C-fiber reflex inhibition. In the ipsilateral local acupoint, the general behavior of the C-fiber reflex can be depressed by electroacupuncture below the threshold of Adelta-fiber activation. Electroacupuncture stimulation within the intensity of Adelta-fiber activation applied to the ipsilateral limb pretreated with cobra venom did not elicit inhibition of C-fiber reflex in rats with demyelinated sciatic nerve. However, heterotopic electroacupuncture below the threshold of Adelta-fiber activation was totally ineffective. In contralateral heterotopic acupoints, the C-fiber reflex can be depressed only by electroacupuncture with stimulating intensities exceeding thresholds of Adelta and C-fiber activation. Electroacupuncture stimuli applied to capsaicin-pretreated limb in the intensities of threshold of Adelta-fiber and treble thresholds of C-fiber activation produced only a little inhibition of C-fiber reflex. Inhibitory intensity was roughly similar to that induced by the stimulation with intensity for the activation of Adelta-fiber in normal animal. In the spinalized animals transections at T6-T7 segments, regardless of intensities, the homotopic electroacupuncture stimulation only induced moderate depression of C-fiber reflex similar to that of Adelta-fiber activation; whereas, no matter what intensities of application, the inhibitory effects of C-fiber reflex disappeared totally by using heterotopic noxious electroacupuncture in these animals.

Pulsed radiofrequency of the sural nerve for the treatment of chronic ankle pain.

BACKGROUND: The application of radiofrequency (RF) has been successfully used in the treatment of chronic pain conditions, including facet arthropathy, sacroiliac joint pain, groin pain, radicular pain, cervicogenic headaches, and phantom limb pain. Due to the neurodestructive effect of continuous RF ablation and possible deafferentation sequelae, only pulsed radiofrequency (PRF) has been applied to peripheral sensory nerves. There are no previous reports of successful PRF application to the sural nerve. OBJECTIVES: To report on the successful use of PRF to the sural nerve for the treatment of ankle pain. To discuss current theories on the mechanism by which PRF produces pain relief. METHODS: The report presented here describes the case of a 39-year old patient who sustained injury to her ankle. The patient was complaining of pain in the distribution of the sural nerve, which was confirmed by electrodiagnostic studies. The pain did not respond to oral and topical analgesics. The patient had short-term relief with a sural block with bupivacaine and triamcinolone. The patient then underwent PRF application to the right sural nerve for 240 seconds at 45 volts. RESULTS: The patient reported complete relief. There was no pain recurrence 5 months after the procedure. LIMITATIONS: This report describes a single case report. CONCLUSIONS: It is conceivable that PRF may provide long-term pain relief in cases of sural nerve injury. The exact mechanism of the antinociceptive effect is still unknown. Possible mechanisms include changes in molecular structure by the electric field, early gene expression, stimulation of descending inhibitory pathways, and transient inhibition of excitatory transmission.

Preliminary report of the effect of high-dose adjuvant intensity modulated radiation therapy on the sural nerve graft for cavernosal nerve sacrifice after radical prostatectomy.

PURPOSE: A sural nerve graft may replace a killed cavernosal nerve. The effect of intensity-modulated radiation therapy (IMRT) on function of the graft has not been reported. MATERIALS AND METHODS: Between 1998 and 2001, 8 patients (9 nerve grafts) were treated with postoperative IMRT (mean dose, 70 Gy). Two patients had neoadjuvant Lupron 30 mg 2 months prior to radiation. Potency was defined as ability to achieve spontaneous erection sufficient for vaginal penetration. Median follow-up was 31.6 months. RESULTS: Five patients (62.5%) who had erectile function after prostatectomy preserved spontaneous erectile function after radiation. Of these, 3 patients had both nerves resected (two receiving unilateral grafts and one receiving bilateral grafts) and 2 others had one graft and one nerve preserved. The impotent patients were impotent after surgery. CONCLUSION: High-dose postprostatectomy IMRT does not place sural nerve grafts at greater risk for failure. Larger numbers of patients are needed to confirm these encouraging, preliminary findings.

Plantar cutaneous input modulates differently spinal reflexes in subjects with intact and injured spinal cord.

STUDY DESIGN: Spinal reflex excitability study in sensory-motor incomplete spinal cord-injured (SCI) and spinal intact subjects. OBJECTIVES: To investigate the effects of plantar cutaneous afferent excitation on the soleus H-reflex and flexion reflex in both subject groups while seated. SETTING: Rehabilitation Institute of Chicago and City University of New York, USA. METHODS: The flexion reflex in SCI subjects was elicited by non-nociceptive stimulation of the sural nerve. In normal subjects, it was also elicited via innocuous medial arch foot stimulation. In both cases, reflex responses were recorded from the ipsilateral tibialis anterior muscle. Soleus H-reflexes were elicited and recorded via conventional methods. Both reflexes were conditioned by plantar cutaneous afferent stimulation at conditioning test intervals ranging from 3 to 90 ms. RESULTS: Excitation of plantar cutaneous afferents resulted in facilitation of the soleus H-reflex and late flexion reflex in SCI subjects. In normal subjects, the soleus H-reflex was depressed while the late flexion reflex was absent. The early flexion reflex was irregularly observed in SCI patients, while in normal subjects a bimodal reflex modulation pattern was observed. CONCLUSION: The effects of plantar cutaneous afferents change following a lesion to the spinal cord leading to exaggerated activity in both flexors and extensors. This suggests impaired modulation of the spinal inhibitory mechanisms involved in the reflex modulation. Our findings should be considered in programs aimed to restore sensorimotor function and promote recovery in these patients. SPONSORSHIP: NIH, NICHD, Grant no. 1R03 HD 043951-01 and PSC CUNY Research Award no. 67051-0036.

Evidence of changes in sural nerve conduction mediated by light emitting diode irradiation.

The introduction of light emitting diode (LED) devices as a novel treatment for pain relief in place of low-level laser warrants fundamental research on the effect of LED devices on one of the potential explanatory mechanisms: peripheral neurophysiology in vivo. A randomised controlled study was conducted by measuring antidromic nerve conduction on the peripheral sural nerve of healthy subjects (n=64). One baseline measurement and five post-irradiation recordings (2-min interval each) were performed of the nerve conduction velocity (NCV) and negative peak latency (NPL). Interventional set-up was identical for all subjects, but the experimental group (=32) received an irradiation (2 min at a continuous power output of 160 mW, resulting in a radiant exposure of 1.07 J/cm(2)) with an infrared LED device (BIO-DIO preprototype; MDB-Laser, Belgium), while the placebo group was treated by sham irradiation. Statistical analysis (general regression nodel for repeated measures) of NCV and NPL difference scores, revealed a significant interactive effect for both NCV (P=0.003) and NPL (P=0.006). Further post hoc LSD analysis showed a time-related statistical significant decreased NCV and an increased NPL in the experimental group and a statistical significant difference between placebo and experimental group at various points of time. Based on these results, it can be concluded that LED irradiation, applied to intact skin at the described irradiation parameters, produces an immediate and localized effect upon conduction characteristics in underlying nerves. Therefore, the outcome of this in vivo experiment yields a potential explanation for pain relief induced by LED.

Effects of electrically induced muscle contraction on flexion reflex in human spinal cord injury.

STUDY DESIGN: Flexion reflex study in motor complete human spinal cord injury (SCI). OBJECTIVES: To examine changes in the magnitude of the flexion reflex following functional electrical stimulation (FES) of the rectus femoris (RF) muscle. SETTING: Bioengineering Unit, University of Strathclyde, Glasgow, Scotland, UK. METHODS: The flexion reflex was evoked by electrical stimulation of the sural nerve, and was recorded in the tibialis anterior (TA) muscle. RF muscle conditioning stimulation was performed at 0.7, 1, and 2 times motor threshold ( x MT) over a range of conditioning test intervals. RESULTS: The incidence of the early component of the flexion reflex (<100 ms) was low, suggesting that this reflex component might be suppressed in SCI. The long latency flexion reflex component (>120 ms) was observed in all subjects during control conditions and following sensorimotor conditioning. FES applied to the RF muscle (above and below MT) in the main induced a significant early and long lasting depression of the long latency flexion reflex. CONCLUSION: The depression of the flexion reflex was a result of multisensory actions on flexion reflex pathways resulting from the direct and indirect (mechanical) consequences of electrically induced muscle contraction on cutaneous and muscle afferents. Our findings emphasize the importance of sensory feedback mechanisms in modulating flexion reflex excitability, and highlight the need for rehabilitation professionals to consider the central actions of FES-induced afferent feedback when incorporating FES into a rehabilitation program. SPONSORSHIP: State Scholarships Foundation (IKY) of Hellas.

Cord dorsum potentials suppressed by low power laser irradiation on a peripheral nerve in the cat.

The effects of low-power helium-neon laser irradiation on the cord dorsum potentials (CDP) evoked by electrical nerve stimulation of a distal portion of exposed sural nerve were observed in unanesthetized decerebrate cats. These evoked CDP were significantly suppressed (25.6 +/- 2.5%, p less than 0.01) during low-power laser irradiation. It is suggested that the analgesic effects of low power laser irradiation is based on the decrease of ascending signals from the spinal cord to the higher central nervous system. The suppressive effect of low power laser irradiation upon the impulse transmission of nerve fibers is discussed.

Effect of low-power laser irradiation on impulse conduction in anesthetized rabbits.

Low-power laser analgesic effect was generally accepted in clinical cases, whereas there was no direct evidence to indicate that low-power laser irradiation suppressed an impulse conduction within a peripheral nerve. The effect of low-power laser irradiation on electrically evoked responses within the sural nerve was electrophysiologically analyzed in anesthetized rabbits. High threshold evoked responses (conduction velocity was about 11 m/sec, unmyelinated A delta), which were induced by an electrical stimulation to the peripheral stump of the nerve, were significantly suppressed (9 to 19% inhibition) during low-power laser irradiation, which applied to the exposed sural nerve between the stimulus site and the recording site. The suppressive effect was reversible and recovered to the control level after the irradiation. Experimental evidence indicated that low-power laser irradiation suppressed the impulse conduction of unmyelinated A delta afferents in peripheral sensory nerve, which caused a pain sensation. Our data suggest that low-power laser acts as a reversible direct suppressor of neuronal activity.

Topographic analysis of painful laser and sural nerve electrical evoked potentials.

A quantitative scalp topographic pattern analysis was used to compare evoked potentials elicited by painful laser (LEP) and electrical stimulation of the sural nerve (snSEP) in 22 healthy adults. The snSEP and LEP were separated into stable periods (consecutive time points having the same topographic pattern). The topographic pattern is dependent upon the number, location, orientation and relative magnitudes of the brain areas active at that time (source configuration). Demonstrating that 2 topographies have the same topographic pattern, therefore, provides evidence that they are generated by the same source configuration. The snSEP SP2/3 and SP3 stable periods have similar topographic features as the stable periods encompassing the LEP N1 and N2 peaks. However, the quantitative scalp topographic analysis demonstrated that the snSEP SP2/3 and SP3 have a much larger fronto-central negativity. Our earlier work suggests this difference might be due to the sural nerve electrical stimulus evoking a more robust pain-evoked response from the anterior cingulate cortex than the laser. The snSEP SP6 topographic pattern was essentially the same as the LEP P2 peak. This finding plus the results of our earlier work demonstrate that SP6 is the snSEP analogue of the LEP P2 peak. These findings have important implications for the choice of evoking stimulus in investigations of pain processing in humans. For example, the sural nerve electrical stimulus will be preferred over the laser in studies of the anterior cingulate's role in cognitive processes related to pain, such as orienting attention, and/or in studies involving cognitive tasks that require the presentation of a large number of painful stimuli. The LEP N1 and N2 peaks, on the other hand, will be preferred in studies of the parietal operculum's role in pain sensation.

Effect of rhythmic arm movement on reflexes in the legs: modulation of soleus H-reflexes and somatosensory conditioning.

During locomotor tasks such as walking, running, and swimming, the arms move rhythmically with the legs. It has been suggested that connections between the cervical and lumbosacral spinal cord may mediate some of this interlimb coordination. However, it is unclear how these interlimb pathways modulate reflex excitability during movement. We hypothesized that rhythmic arm movement would alter the gain of reflex pathways in the stationary leg. Soleus H-reflexes recorded during arm cycling were compared with those recorded at similar positions with the arms stationary. Nerve stimulation was delivered with the right arm at approximately 70 degrees shoulder flexion or 10 degrees shoulder extension. H-reflexes were evoked alone (unconditioned) or with sural or common peroneal nerve (CP) conditioning to decrease or increase soleus IA presynaptic inhibition, respectively. Both conditioning stimuli were also delivered with no H-reflex stimulation. H-reflex amplitudes were compared at similar M-wave amplitudes and activation levels of the soleus. Arm cycling significantly reduced (P < 0.05) unconditioned soleus H-reflexes at shoulder flexion by 21.7% and at shoulder extension by 8.8% compared with static controls. The results demonstrate a task-dependent modulation of soleus H-reflexes between arm cycling and stationary trials. Sural nerve stimulation facilitated H-reflexes at shoulder extension but not at shoulder flexion during static and cycling trials. CP nerve stimulation significantly reduced H-reflex amplitude in all conditions. Reflexes in soleus when sural and CP nerve stimulation were delivered alone, were not different between cycling and static trials; thus the task-dependent change in H reflex amplitude was not due to changes in motoneuron excitability. Therefore modulation occurred at a pre-motoneuronal level, probably by presynaptic inhibition of the IA afferent volley. Results indicate that neural networks coupling the cervical and lumbosacral spinal cord in humans are activated during rhythmic arm movement. It is proposed that activation of these networks may assist in reflex linkages between the arms and legs during locomotor tasks.

A novel RAB7 mutation associated with ulcero-mutilating neuropathy.

There are two known autosomal dominant genes for the hereditary ulcero-mutilating neuropathies: SPTLC1 (hereditary sensory neuropathy type 1) and RAB7 (Charcot-Marie-Tooth disease type 2B). We report a family with autosomal dominant ulcero-mutilating neuropathy, developing in the teens and characterized by ulcers, amputations, sensory involvement in the feet but no motor features. Sequencing the RAB7 gene showed a novel heterozygous A to C mutation, changing asparagine to threonine at codon 161. The mutation is situated adjacent to a previously identified valine to methionine mutation at codon 162, implying a hotspot for mutations in the highly conserved C terminus of RAB7.