[Structural changes in the sensory ganglia of the spinal nerves after repeated magnetic stimulation on the model of ischemic myelopathy].

The aim of this study was to examine the association of morphological changes in the-sensory ganglia of the spinal nerves (SGSN) with the cilinical symptomatology in rats with the experimentally induced ischemic myelopathy (IM), untreated or treated with repeated magnetic stimulation (RMS). The efficacy and mechanisms of RMS action on SGSN were studied by electron microscopy in 16 rats with IM. According to the results of treatment, in SGSN both at a distance from the damaged area (lumbar SGSN) and close to it (cervical SGSN) the morphological signs of regenerative-reparative processes were found in the cells and nerve fibers (restoration of the organelle structure in the cytoplasm o0f neurons and neurolemmocytes, the increase in the number of he latter and fiber remyelination). The expression of the structural changes correlated with the degree of functional recovery.

Effects From Nonuniform Dose Distribution in the Spinal Nerves of Pigs: Analysis of Normal Tissue Complication Probability Models.

PURPOSE: Our purpose was to evaluate normal tissue complication probability (NTCP) models for their ability to describe the increase in tolerance as the length of irradiated spinal nerve is reduced in a pig. METHODS AND MATERIALS: Common phenomenological and semimechanistic NTCP models were fit using the maximum likelihood estimate method to dose-response data from spinal nerve irradiation studies in pigs. Statistical analysis was used to compare how well each model fit the data. Model parameters were then applied to a previously published dose distribution used for spinal cord irradiation in rats under the assumption of a similar dose-response. RESULTS: The Lyman-Kutcher-Burman model, relative seriality, and critical volume model fit the spinal nerve data equally well, but the mean dose logistic and relative seriality models gave the best fit after penalizing for the number of model parameters. The minimum dose logistic regression model was the only model showing a lack of fit. When extrapolated to a 0.5-cm simulated square-wave-like dose distribution, the serial behaving models showed negligible increase in dose-response curve. The Lyman-Kutcher-Burman model and relative seriality models showed significant shifting of NTCP curves due to parallel behaving parameters. The critical volume model gave the closest match to the rat data. CONCLUSIONS: Several phenomenological and semimechanistic models were observed to adequately describe the increase in the radiation tolerance of the spinal nerves when changing the irradiated length from 1.5 to 0.5 cm. Contrary to common perception, model parameters suggest parallel behaving tissue architecture. Under the assumption that the spinal nerve response to radiation is similar to that of the spinal cord, only the critical volume model was robust when extrapolating to outcome data from a 0.5-cm square-wave-like dose distribution, as was delivered in rodent spinal cord irradiation research.

Existence of a Dose-Length Effect in Spinal Nerves Receiving Single-Session Stereotactic Ablative Radiation Therapy.

PURPOSE: The spinal nerves have been observed to have a similar single-session dose tolerance to that of the spinal cord in pigs. Small-animal studies have shown that spinal cord dose tolerance depends on the length irradiated. This work aims to determine whether a dose-length effect exists for spinal nerves. METHODS AND MATERIALS: Twenty-seven Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 0.5 cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. The pigs were distributed into 6 groups with prescription doses of 16 Gy (n = 5), 18 Gy (n = 5), 20 Gy (n = 5), 22 Gy (n = 5), 24 Gy (n = 5), or 36 Gy (n = 2) and corresponding maximum doses of 16.7, 19.1, 21.3, 23.1, 25.5, and 38.6 Gy, respectively. Neurologic status was assessed with a serial electrodiagnostic examination and daily observation of gait for approximately 52 weeks. A histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff's staining was also performed. RESULTS: Marked gait change was observed in 8 of 27 irradiated pigs. The latency for responding pigs was 11 to 16 weeks after irradiation. The affected animals presented with a limp in the left front limb, and 62.5% of these pigs had electrodiagnostic evidence of denervation in the C6 and C7 innervated muscles. A probit analysis showed the dose associated with a 50% incidence of gait change is 23.9 Gy (95% confidence interval, 22.5-25.8 Gy), which is 20% higher than that reported in a companion study where a 1.5 cm length was irradiated. All symptomatic pigs had demyelination and fibrosis in the irradiated nerves, but the contralateral nerves and spinal cord were normal. CONCLUSIONS: A dose-length effect was observed for single-session irradiation of the spinal nerves in a Yucatan minipig model.

Spinal Nerve Tolerance to Single-Session Stereotactic Ablative Radiation Therapy.

PURPOSE: This study was performed to determine the dose-related incidence of neuropathy from single-session irradiation of the C6-C8 spinal nerves using a pig model and to test the hypothesis that the spinal nerves and spinal cord have the same tolerance to full cross-sectional irradiation. METHODS AND MATERIALS: Twenty-five Yucatan minipigs received study treatment. Each animal underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 1.5-cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. Pigs were distributed into 5 groups with prescription doses of 16 (n = 7), 18 (5), 20 (5), 22 (5), or 24 (3) Gy with corresponding maximum nerve doses of 17.3, 19.5, 21.6, 24.1, and 26.2 Gy. The neurologic status of all animals was followed for approximately 52 weeks by serial electrodiagnostic examination and daily observation of gait. Histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff staining was performed on bilateral spinal nerves and the spinal cord. RESULTS: Marked gait change was observed in 15 of the 25 irradiated pigs. Affected animals presented with a limp in their left front limb, and electromyography demonstrated evidence of denervation in C6 and C7 innervated muscles. Probit analysis showed the ED50 for gait change after irradiation of the spinal nerves to be 19.7 Gy (95% confidence interval, 18.5-21.1). The latency for all responding pigs was 9 to 15 weeks after irradiation. All symptomatic pigs had demyelination and fibrosis in their irradiated nerves, whereas contralateral nerves and spinal cord were normal. CONCLUSIONS: The ED50 for symptomatic neuropathy after full cross-sectional irradiation of the spinal nerves was found to be 19.7 Gy. The dose response of the C6-C8 spinal nerves is not significantly different from that of full cross-sectional irradiation of the spinal cord as observed in companion studies.

Somatostatin inhibits activation of dorsal cutaneous primary afferents induced by antidromic stimulation of primary afferents from an adjacent thoracic segment in the rat.

To investigate the effect of somatostatin on the cross-excitation between adjacent primary afferent terminals in the rats, we recorded single unit activity from distal cut ends of dorsal cutaneous branches of the T10 and T12 spinal nerves in response to antidromic stimulation of the distal cut end of the T11 dorsal root in the presence and absence of somatostatin and its receptor antagonist applied to the receptive field of the recorded nerve. Afferent fibers were classified based upon their conduction velocity. Mean mechanical thresholds decreased and spontaneous discharge rates increased significantly in C and Adelta but not Abeta fibers of the T10 and T12 spinal nerves in both male and female rats following antidromic electrical stimulation (ADES) of the dorsal root from adjacent spinal segment (DRASS) indicating cross-excitation of thin fiber afferents. The cross-excitation was not significantly different between male and female rats. Microinjection of somatostatin into the receptive field of recorded units inhibited the cross-excitation. This inhibitory effect, in turn, was reversed by the somatostation receptor antagonist cyclo-somatostatin (c-SOM). Application of c-SOM alone followed by ADES of DRASS significantly decreased the mechanical thresholds and increased the discharge rates of C and Adelta fibers, indicating that endogenous release of somatostatin plays a tonic inhibitory role on the cross-excitation between peripheral nerves. These results suggest that somatostatin could inhibit the cross-excitation involved in peripheral hyperalgesia and have a peripheral analgesic effect.

Effects of spinal cord stimulation on the cortical somatosensory evoked potentials in failed back surgery syndrome patients.

OBJECTIVE: To evaluate the functional activation of the somatosensory cortical regions in neuropathic pain patients during therapeutic spinal cord stimulation (SCS). METHODS: In nine failed back surgery syndrome patients, the left tibial and the left sural nerves were stimulated in two sessions with intensities at motor and pain thresholds, respectively. The cortical somatosensory evoked potentials were analyzed using source dipole analysis based on 111 EEG signals. RESULTS: The short-latency components of the source located in the right primary somatosensory cortex (SI: 43, 54 and 65ms) after tibial nerve stimulation, the mid-latency SI component (87ms) after sural nerve stimulation, and the mid-latency components in the right (approximately 161ms) and left (approximately 168ms) secondary somatosensory cortices (SII) were smaller in the presence of SCS than in absence of SCS. The long-latency source component arising from the mid-cingulate cortex (approximately 313ms) was smaller for tibial and larger for sural nerve stimuli during SCS periods compared to periods without SCS. CONCLUSIONS: SCS attenuates the somatosensory processing in the SI and SII. In the mid-cingulate cortex, the effect of SCS depends on the type of stimulation and nerve fibers involved. SIGNIFICANCE: Results suggest that the effects of SCS on cortical somatosensory processing may contribute to a reduction of allodynia during SCS.

Involvement of peripheral ionotropic glutamate receptors in activation of cutaneous branches of spinal dorsal rami following antidromic electrical stimulation of adjacent afferent nerves in rats.

The aim of the present study was to investigate the role of peripheral ionotropic glutamate receptors in the process of signal transmission between adjacent different peripheral sensory nerves. The T9 and T10 cutaneous branches of spinal dorsal rami were dissociated and cut proximally in pentobarbital anesthetized rats. Eighty-seven single afferents from T10 nerve filaments were recorded and characterized by assessing their spontaneous activities. Following 30 s antidromic electrical stimulation (intensity: 1 mA; duration: 0.5 ms; frequency: 20 Hz) of T9 cutaneous branches, the spontaneous activities of Abeta, Adelta and C fibers of T10 nerve were significantly enhanced from 2.00+/-0.34, 2.42+/-0.33, and 2.19+/-0.32 impulses/min to 4.31+/-0.58, 5.22+/-0.55, and 5.27+/-0.69 impulses/min, respectively (n=29 for each type, P<0.05). These enhanced spontaneous discharges of T10 nerve were significantly blocked by local treatment of its receptive field with either N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 or non-NMDA receptor antagonist DNQX (0.1 mM, 10 microl for each drug) (P<0.05). These results suggest that peripheral ionotropic glutamate receptors are involved in the activation of peripheral nerves following the antidromic stimulation of adjacent afferents from different spinal segments. We further provide the direct evidence that neurotransmitters released from adjacent peripheral nerves may also contribute to the occurrence of allodynia as well as secondary hyperalgesia during the pathological nociception.

Sacral neuromodulation as a functional treatment of bladder overactivity.

Sacral neuromodulation, namely the electrical stimulation of the sacral nerves has become an alternative treatment for cases of idiopathic bladder overactivity. The mechanism of action in this type of spinal cord modulation is only partially understood but it seems to involve stimulation of inhibitory interneurons. Temporary sacral nerve stimulation is the first step. It consists of the temporary application of neurostimulation as a diagnostic test in order to check the integrity of the sacral root and determine the best location for the implant. If the test stimulation is successful, a permanent device is implanted. In experienced hands, this is a safe procedure. When the patients are selected on the basis of sound criteria, more than three-quarters of them show a clinically significant improvement with a reduction in the frequency of incontinence episodes by more than 50%; however, the results vary according to each author's method of evaluation. The application of this technique should be combined with careful follow-up and attentive adjustments of the stimulation parameters in order to optimize the coordination of activity between the neurological systems involved.

Release of GABA from sensory neurons transduced with a GAD67-expressing vector occurs by non-vesicular mechanisms.

We have demonstrated that dorsal root ganglion neurons transduced with a recombinant replication-defective herpes simplex virus vector coding for glutamic acid decarboxylase (QHGAD67) release GABA to produce an analgesic effect in rodent models of pain. In this study, we examined the mechanism of transgene-mediated GABA release from dorsal root ganglion neurons in vitro and in vivo. Release of GABA from dorsal root ganglion neurons transduced with QHGAD67 was not increased by membrane depolarization induced by 60 mM extracellular K+ nor reduced by the removal of Ca2+ from the medium. Release of GABA from transduced dorsal root ganglion neurons was, however, blocked in a dose-dependent manner by NO-711, a selective inhibitor of the GABA transporter-1. The amount of GABA released from a spinal cord slice preparation, prepared from animals transduced by subcutaneous inoculation of QHGAD67 in the hind paws, was substantially increased compared to animals transduced with control vector Q0ZHG or normal animals, but the amount of GABA released was not changed by stimulation of the dorsal roots at either low (0.1 mA, 0.5-ms duration) or high (10 mA, 0.5-ms duration) intensity. We conclude that QHGAD67-mediated GABA release from dorsal root ganglion neurons is non-vesicular, independent of electrical depolarization, and that this efflux is mediated through reversal of the GABA transporter.

Pulsed radiofrequency inhibited activation of spinal mitogen-activated protein kinases and ameliorated early neuropathic pain in rats.

Background: Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer knowledge is available in its impact on glia-mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury-induced pain development and activation of spinal mitogen-activated protein kinases (MAPKs). Methods: In a rat spinal nerve ligation (SNL) model, a low-volt PRF treatment was applied to the L5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. MAPK activations, including p-ERK and p-p38, as well as TNF-á level in the spinal dorsal horn were assessed and the cell types that expressed MAPK activation were identified by double immuno fluorescence staining.Results: We found that SNL promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p-ERK and p-p38 in the spinal dorsal horn. PRF significantly attenuated SNL-induced mechanical allodynia and thermal hyperalgesia for 5­7 days. PRF also inhibited ERK and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, PRF significantly suppressed expression of TNF-á in the spinal dorsal horn throughout the course. Conclusions: Low-volt PRF significantly ameliorated SNL-induced acute pain. Inferentially, PRF may inhibit spinal sensitization by down-regulating spinal MAPK activations and activation-mediated cytokine release.We demonstrated that early PRF treatment in acute nerve injury helps to ameliorate neuropathic pain development.

Paralysis following stereotactic spinal irradiation in pigs suggests a tolerance constraint for single-session irradiation of the spinal nerve.

BACKGROUND AND PURPOSE: Paralysis observed during a study of vertebral bone tolerance to single-session irradiation led to further study of the dose-related incidence of motor peripheral neuropathy. MATERIALS AND METHODS: During a bone tolerance study, cervical spinal nerves of 15 minipigs received bilateral irradiation to levels C5-C8 distributed into three dose groups with mean maximum spinal nerve doses of 16.9 ± 0.3 Gy (n=5), 18.7 ± 0.5 Gy (n=5), and 24.3 ± 0.8 Gy (n=5). Changes developing in the gait of the group of pigs receiving a mean maximum dose of 24.3 Gy after 10-15 weeks led to the irradiation of two additional animals. They received mean maximum dose of 24.9 ± 0.2 Gy (n=2), targeted to the left spinal nerves of C5-C8. The followup period was one year. Histologic sections from spinal cords and available spinal nerves were evaluated. MR imaging was performed on pigs in the 24.9 Gy group. RESULTS: No pig that received a maximum spinal nerve point dose ≤19.0 Gy experienced a change in gait while all pigs that received ≥24.1 Gy experienced paralysis. Extensive degeneration and fibrosis were observed in irradiated spinal nerves of the 24.9 Gy animals. All spinal cord sections were normal. Irradiated spinal nerve regions showed increased thickness and hypointensity on MR imaging. CONCLUSION: The single-session tolerance dose of the cervical spinal nerves lies between 19.0 and 24.1 Gy for this model.

[Non-invasive transcutaneous spinal cord stimulation facilitates locomotor activity in decerebrated and spinal cats].

It is known that spinal neuronal networks activated by epidural electrical stimulation (EES) can produce the stepping EMG pattern and control the locomotor behavior. At present study we showed that non-invasive transcutaneous electrical spinal cord stimulation (tESCS) applied to the lumbar-sacral enlargement can facilitate the locomotor activity in decerebrated and spinal animals. The comparison of the motor responses evoked by EES vs tESCS showed that both methods produce the locomotor patterns with close properties and similar reflex mechanisms. The data obtained suggest that tESCS is an efficient approach for investigation of the locomotor control in acute and chronic experiments as well as facilitates of the locomotor abilities after spinal cord injury. Taking to account the non-invasivity and easement of tESCS, this approach could be further implemented in clinical practice for rehabilitation of the patient with spinal cord injury.

Sacral nerve stimulation: neuromodulation for voiding dysfunction and pain.

Voiding dysfunction, which includes incontinence, retention, and chronic pelvic pain, is a relatively frequent problem that can be difficult to manage. Neuromodulation via stimulation of the sacral nerves has been shown to improve these symptoms, although the exact mechanisms remain elusive. Techniques for nerve stimulation may vary, depending on the disease, location of pain, and the patient's anatomy. In addition to placement of electrodes on the sacral nerve roots, modulation has also been reported by peripheral branches of the sacral nerves including the pudendal and posterior tibial nerves. Newer surgical techniques have significantly decreased the morbidity of the procedures and increased the probability of a successful outcome.

Intradiscal high-voltage, long-duration pulsed radiofrequency for discogenic pain: a preliminary report.

BACKGROUND: Intradiscal radiofrequency, with the electrode placed in the center of the nucleus pulposus, has been a controversial procedure in patients with discogenic pain. Possibly the effect has not been due to the production of heat, but to exposure to electric fields. DESIGN: We have investigated the effect of high-voltage, long-duration intradiscal pulsed radiofrequency in patients with one-level discogenic low back pain, as confirmed by discography. OUTCOME MEASURE: The pain intensity score on a 0-10 numeric rating scale (NRS) was taken as outcome measure. PATIENTS: Eight patients were reported. The mean duration of pain was 6.3 years (range 0.5-16, median 4). The mean NRS score was 7.75 (range 5-9). Disc height was reduced 60% in one patient and up to 30% in the others. INTERVENTION: A 15-cm, 20-gauge needle with a 15-mm active tip was placed centrally in the disc. Pulsed radiofrequency was applied for 20 min at a setting of 2 x 20 ms/s and 60 V. RESULTS: There was a very significant fall in the NRS scores over the first 3 months (P < 0.0001). On an individual basis, all patients had a fall of the NRS score of at least 4 points at the 3-month follow-up. A follow-up of 12.8 months (range 6-25, median 9) was available for five patients. All these patients are now pain free, except for one patient with an NRS score of 2. Conclusion. It is concluded that this method merits a controlled, prospective study.

Pulsed radiofrequency denervation for the treatment of sacroiliac joint syndrome.

OBJECTIVE: Current therapies for sacroiliac joint (SIJ) dysfunction offer discouraging results in alleviating low back pain. The innervation and target nerves for radiofrequency denervation (RFD) of the SIJ remain unclear. We present a prospective case series on the treatment of intractable SIJ dysfunction with pulsed radiofrequency denervation (PRFD) of lateral branches from L4-S3. INTERVENTIONS: A total of 126 patients with presumptive SIJ dysfunction based on history and physical examination underwent arthrographically confirmed steroid/local anesthetic SIJ injection. Fifty-two patients (41.3%) had >75% pain relief after two consecutive injections, physical therapy, repeated SIJ injections, and/or analgesics. Twenty-two patients failed to respond. These patients underwent PRFD of the medial branch of L4, posterior primary rami of L5, and lateral branches S1 and S2. OUTCOME MEASURES: Visual analog score (VAS) and quality of life (QOL) assessments were performed prior to and after treatment. RESULTS: Sixteen patients (72.7%) experienced "Good" (>50% reduction in VAS), or "Excellent" (>80% reduction in VAS) pain relief following PRFD. Duration of pain relief range was 6-9 weeks in four patients, 10-16 weeks in five patients, and 17-32 weeks in seven patients. In addition, QOL scores improved significantly in all measured categories. Six patients (26.1%) did not respond to PRFD and had less than 50% reduction in VAS and were considered failures. CONCLUSIONS: PRFD of the lateral branch of the medial branch of L4, posterior primary rami of L5, and lateral branches S1 and S2 is an effective treatment for some patients with SIJ pain unresponsive to other forms of therapy.

Pulsed radiofrequency treatment of the lumbar medial branch for facet pain: a retrospective analysis.

BACKGROUND: The use of pulsed radiofrequency (PRF) for treatment of the medial branch is controversial. STUDY DESIGN: A retrospective study of the results of PRF treatment of the medial branch in 48 patients with chronic low back pain was carried out. Patients who did not respond were offered treatment with conventional radiofrequency heat lesions. PATIENT MATERIAL: Patients were included who had low back pain and >50% pain relief following a diagnostic medial branch block. The mean age was 53.1 +/- 13.5 years, the mean duration of pain was 11.4 +/- 10.9 years (range 2-50). Nineteen patients had undergone surgery. METHODS: Pain scores on a numeric rating scale of 1-10 were noted before and after the diagnostic nerve block, before the procedure, and at 1-month and 4-month follow-up. PRF was applied for 2 minutes at a setting of 2 x 20 ms/s and 45 V at a minimum of two levels using a 22G electrode with a 5 mm active tip. Heat lesions were made at 80 degrees C for 1 minute. OUTCOME DEFINITION: A successful outcome was defined as a >60% improvement on the numeric rating scale at 4-month follow-up. RESULTS: In 21/29 nonoperated patients and 5/19 operated patients, the outcome was successful. In the unsuccessful patients who were subsequently treated with heat lesions, the success rate was 1/6. CONCLUSION: The setup of our study does not permit a comparison with the results of continuous radiofrequency (CRF) for the same procedure, other than the detection of an obvious trend. When comparing our results with various studies on CRF of the medial branch such a trend could not be found. Based on these retrospective data, prospective and randomized trials, for example, radiofrequency vs PRF are justified.

A case of pulsed radiofrequency lesioning for occipital neuralgia.

OBJECTIVE: This report describes a case where pulsed radiofrequency lesioning (RFL) of the greater occipital nerve (GON) offered a valuable and safe treatment for the management of greater occipital neuralgia. The case is considered in relation to a review of the medical literature on greater occipital neuralgia and RFL interventions. CASE REPORT: A 62-year-old man with a 43-year history of left suboccipital pain underwent pulsed RFL of the left GON (20-millisecond bursts at intervals of 0.5 second for 4 minutes at 42 degrees C) after failing to achieve substantial analgesia with naproxen, a transcutaneous electrical nerve stimulator (TENS) unit and a greater occipital nerve blockade (GONB) utilizing local anesthetic and steroid. After obtaining 4 months of 70% pain relief, pulsed RFL was repeated and resulted in an additional 5 months of 70% pain relief. CONCLUSIONS: Pulsed RFL of the GON is an alternative to continuous RFL with the proposed advantage of mitigating pain, as in continuous RFL, but without the potential risk of causing deafferentation pain. While placebo and other nonspecific analgesic effects cannot be ruled out, the apparent safety profile and potential efficacy of pulsed RFL suggests it may be a compelling option to consider before irreversible neuroablative therapies are applied.

Effect of pulsed Nd:YAG laser radiation on action potential conduction in isolated mammalian spinal nerves.

BACKGROUND AND OBJECTIVE: Dental lasers are claimed to produce analgesia, but the mechanisms and extent of any effects are uncertain. This study investigated the effects of lasing on nerve conduction in isolated nerves. STUDY DESIGN/MATERIALS AND METHODS: Pulsed Nd:YAG laser energy was applied to spinal nerves in vitro and effects were measured as attenuation of the compound action potential (CAP) evoked by electrical stimulation. RESULTS: Lasing for 1 minute at 0.3-3.0 W caused a dose-dependent attenuation of all components of the CAP (P < 0.03). With 0.3-1.0 W power, the CAP recovered to > 95% of the control levels 7 minutes after lasing; recovery was incomplete after lasing at > 2.0 W. CONCLUSION: Isolated nerves were remarkably tolerant of lasing. The degree of nerve conduction block increased with laser power. The data indicate that lasing could diminish sensations, including pain, mediated by peripheral nerves in soft tissues.