Effect of sympathetic sprouting on the excitability of dorsal root ganglion neurons and afferents in a rat model of neuropathic pain.

Increased sympathetic nerve excitability has been reported to aggravate a variety of chronic pain conditions, and an increase in the number of sympathetic nerve fibers in the dorsal root ganglion (DRG) has been found in neuropathic pain (NP) models. However, the mechanism of the neurotransmitter norepinephrine (NE) released by sympathetic nerve fiber endings on the excitability of DRG neurons is still controversial, and the adrenergic receptor subtypes involved in this biological process are also controversial. In our study, we have two objectives: (1) To determine the effect of the neurotransmitter NE on the excitability of different neurons in DRG; (2) To determine which adrenergic receptors are involved in the excitability of DRG neurons by NE released by sprouting sympathetic fibers. In this experiment, a unique field potential recording method of spinal cord dorsal horn was innovatively adopted, which can be used for electrophysiological study in vivo. The results showed that： Forty days after SNI, patch clamp and field potential recording methods confirmed that NE enhanced the excitability of ipsilateral DRG large neurons, and then our in vivo electrophysiological results showed that the α2 receptor blocker Yohimbine could block the excitatory effect of NE on A-fiber and the inhibitory effect on C-fiber, while the α2A-adrenergic receptor agonist guanfacine (100 µM) had the same biological effect as NE. Finally, we concluded that NE from sympathetic fiber endings is involved in the regulation of pain signaling by acting on α2A-adrenergic receptors in DRG.

PCC-0105002, a novel small molecule inhibitor of PSD95-nNOS protein-protein interactions, attenuates neuropathic pain and corrects motor disorder associated with neuropathic pain model.

In view of postsynaptic density 95kDA (PSD95) tethers neuronal NO synthase (nNOS) to N-methyl-d-aspartate receptor (NMDAR), the PSD95-nNOS complex represents a therapeutic target of neuropathic pain. This study therefore sought to explore the ability of PCC-0105002, a novel PSD95-nNOS small molecule inhibitor, to alter pain sensitivity in rodent neuropathic pain models. Firstly, the IC50 of PCC-0105002 for PSD95 and NOS1 binding activity was determined using an Alpha Screen assay kit. Then, we examined the effects of PCC-0105002 in the mouse formalin test and in the rat spinal nerve ligation (SNL) model, and explored the ability of PCC-0105002 to mediate analgesia and to effect motor coordination in a rota-rod test. Moreover, the mechanisms whereby PCC-0105002 mediates analgesia was explored via western blotting, Golgi staining, and co-immunoprecipitation experiments in dorsal horn. The outcomes indicated that PCC-0105002 exhibited dose-dependent attenuation of phase II pain-associated behaviors in the formalin test. The result indicated that PCC-0105002 disrupted the PSD95-nNOS interaction with IC50 of 1.408 µM. In the SNL model, PCC-0105002 suppressed mechanical allodynia, thermal hyperalgesia, and abnormal dorsal horn wide dynamic range neuron discharge. PCC-0105002 mediated an analgesic effect comparable to that of MK-801, while it was better able to enhance motor coordination as compared with MK-801. Moreover, PCC-0105002 altered signaling downstream of NMDAR and thus functionally and structurally attenuating synaptic plasticity through respective regulation of the NR2B/GluR1/CaMKIIα and Rac1/RhoA pathways. These findings suggest that the novel PSD95-nNOS inhibitor PCC-0105002 is an effective agent for alleviating neuropathic pain, and that it produces fewer motor coordination-associated side effects than do NMDAR antagonists.

Plasticity of the Injured Spinal Cord.

Complete spinal cord injury (SCI) leads to permanent motor, sensitive and sensory deficits. In humans, there is currently no therapy to promote recovery and the only available treatments include surgical intervention to prevent further damage and symptomatic relief of pain and infections in the acute and chronic phases, respectively. Basically, the spinal cord is classically viewed as a nonregenerative tissue with limited plasticity. Thereby the establishment of the "glial" scar which appears within the SCI is mainly described as a hermetic barrier for axon regeneration. However, recent discoveries have shed new light on the intrinsic functional plasticity and endogenous recovery potential of the spinal cord. In this review, we will address the different aspects that the spinal cord plasticity can take on. Indeed, different experimental paradigms have demonstrated that axonal regrowth can occur even after complete SCI. Moreover, recent articles have demonstrated too that the "glial" scar is in fact composed of several cellular populations and that each of them exerts specific roles after SCI. These recent discoveries underline the underestimation of the plasticity of the spinal cord at cellular and molecular levels. Finally, we will address the modulation of this endogenous spinal cord plasticity and the perspectives of future therapeutic opportunities which can be offered by modulating the injured spinal cord microenvironment.

Spinal microglial ß-endorphin signaling mediates IL-10 and exenatide-induced inhibition of synaptic plasticity in neuropathic pain.

AIM: This study aimed to investigate the regulation of pain hypersensitivity induced by the spinal synaptic transmission mechanisms underlying interleukin (IL)-10 and glucagon-like peptide 1 receptor (GLP-1R) agonist exenatide-induced pain anti-hypersensitivity in neuropathic rats through spinal nerve ligations. METHODS: Neuropathic pain model was established by spinal nerve ligation of L5/L6 and verified by electrophysiological recording and immunofluorescence staining. Microglial expression of ß-endorphin through autocrine IL-10- and exenatide-induced inhibition of glutamatergic transmission were performed by behavioral tests coupled with whole-cell recording of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) through application of endogenous and exogenous IL-10 and ß-endorphin. RESULTS: Intrathecal injections of IL-10, exenatide, and the µ-opioid receptor (MOR) agonists ß-endorphin and DAMGO inhibited thermal hyperalgesia and mechanical allodynia in neuropathic rats. Whole-cell recordings of bath application of exenatide, IL-10, and ß-endorphin showed similarly suppressed enhanced frequency and amplitude of the mEPSCs in the spinal dorsal horn neurons of laminae II, but did not reduce the frequency and amplitude of mIPSCs in neuropathic rats. The inhibitory effects of IL-10 and exenatide on pain hypersensitive behaviors and spinal synaptic plasticity were totally blocked by pretreatment of IL-10 antibody, ß-endorphin antiserum, and MOR antagonist CTAP. In addition, the microglial metabolic inhibitor minocycline blocked the inhibitory effects of IL-10 and exenatide but not ß-endorphin on spinal synaptic plasticity. CONCLUSION: This suggests that spinal microglial expression of ß-endorphin mediates IL-10- and exenatide-induced inhibition of glutamatergic transmission and pain hypersensitivity via presynaptic and postsynaptic MORs in spinal dorsal horn.

Spontaneous neural synchrony links intrinsic spinal sensory and motor networks during unconsciousness.

Non-random functional connectivity during unconsciousness is a defining feature of supraspinal networks. However, its generalizability to intrinsic spinal networks remains incompletely understood. Previously, Barry et al., 2014 used fMRI to reveal bilateral resting state functional connectivity within sensory-dominant and, separately, motor-dominant regions of the spinal cord. Here, we record spike trains from large populations of spinal interneurons in vivo in rats and demonstrate that spontaneous functional connectivity also links sensory- and motor-dominant regions during unconsciousness. The spatiotemporal patterns of connectivity could not be explained by latent afferent activity or by populations of interconnected neurons spiking randomly. We also document connection latencies compatible with mono- and disynaptic interactions and putative excitatory and inhibitory connections. The observed activity is consistent with the hypothesis that salient, experience-dependent patterns of neural transmission introduced during behavior or by injury/disease are reactivated during unconsciousness. Such a spinal replay mechanism could shape circuit-level connectivity and ultimately behavior.

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 2: correlation between histological changes and nerve evoked contractions.

We determined the effect of pelvic organ decentralization and reinnervation 1 yr later on urinary bladder histology and function. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, eight were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers, then euthanized 8-12 mo later. Four served as long-term decentralized only animals. Before euthanasia, pelvic or transferred nerves and L1-S3 spinal roots were stimulated and maximum detrusor pressure (MDP) recorded. Bladder specimens were collected for histological and ex vivo smooth muscle contractility studies. Both reinnervated and decentralized animals showed less or denuded urothelium, fewer intramural ganglia, and more inflammation and collagen, than controls, although percent muscle was maintained. In reinnervated animals, pgp9.5+ axon density was higher compared with decentralized animals. Ex vivo smooth muscle contractions in response to KCl correlated positively with submucosal inflammation, detrusor muscle thickness, and pgp9.5+ axon density. In vivo, reinnervated animals showed higher MDP after stimulation of L1-L6 roots compared with their transected L7-S3 roots, and reinnervated and decentralized animals showed lower MDP than controls after stimulation of nerves (due likely to fibrotic nerve encapsulation). MDP correlated negatively with detrusor collagen and inflammation, and positively with pgp9.5+ axon density and intramural ganglia numbers. These results demonstrate that bladder function can be improved by transfer of obturator nerves to pelvic nerves at 1 yr after decentralization, although the fibrosis and inflammation that developed were associated with decreased contractile function.

Electroacupuncture may alleviate neuropathic pain via suppressing P2X7R expression.

Neuropathic pain is a severe problem that is difficult to treat clinically. Reducing abnormal remodeling of dendritic spines/synapses and increasing the anti-inflammatory effects in the spinal cord dorsal horn are potential methods to treat this disease. Previous studies have reported that electroacupuncture (EA) could increase the pain threshold after peripheral nerve injury. However, the underlying mechanism is unclear. P2X7 receptors (P2X7R) mediate the activation of microglia and participate in the occurrence and development of neuropathic pain. We hypothesized that the effects of EA on relieving pain may be related to the downregulation of the P2X7R. Spinal nerve ligation (SNL) rats were used as a model in this experiment, and 2'(3')-O-(4-benzoyl)benzoyl ATP (BzATP) was used as a P2X7R agonist. We found that EA treatment decreased dendritic spine density, inhibited synaptic reconstruction and reduced inflammatory response, which is consistent with the decrease in P2X7R expression as well as the improved neurobehavioral performance. In contrast to the beneficial effects of EA, BzATP enhanced abnormal remodeling of dendritic spines/synapses and inflammation. Furthermore, the EA-mediated positive effects were reversed by BzATP, which is consistent with the increased P2X7R expression. These findings indicated that EA improves neuropathic pain by reducing abnormal dendritic spine/synaptic reconstruction and inflammation via suppressing P2X7R expression.

Acetylcholine and spinal locomotor networks: The insider.

This article aims to review studies that have investigated the role of neurons that use the transmitter acetylcholine (ACh) in controlling the operation of locomotor neural networks within the spinal cord. This cholinergic system has the particularity of being completely intraspinal. We describe the different effects exerted by spinal cholinergic neurons on locomotor circuitry by the pharmacological activation or blockade of this propriospinal system, as well as describing its different cellular and subcellular targets. Through the activation of one ionotropic receptor, the nicotinic receptor, and five metabotropic receptors, the M1 to M5 muscarinic receptors, the cholinergic system exerts a powerful control both on synaptic transmission and locomotor network neuron excitability. Although tremendous advances have been made in our understanding of the spinal cholinergic system's involvement in the physiology and pathophysiology of locomotor networks, gaps still remain, including the precise role of the different subtypes of cholinergic neurons as well as their pre- and postsynaptic partners. Improving our knowledge of the propriospinal cholinergic system is of major relevance to finding new cellular targets and therapeutics in countering the debilitating effects of neurodegenerative diseases and restoring motor functions after spinal cord injury.

Diabetic Neuropathy Influences Control of Spinal Mechanisms.

PURPOSE: Comprehensive evaluation of the upstream sensory processing in diabetic symmetrical polyneuropathy (DSPN) is sparse. The authors investigated the spinal nociceptive withdrawal reflex and the related elicited somatosensory evoked cortical potentials. They hypothesized that DSPN induces alterations in spinal and supraspinal sensory-motor processing compared with age- and gender-matched healthy controls. METHODS: In this study, 48 patients with type 1 diabetes and DSPN were compared with 21 healthy controls. Perception and reflex thresholds were determined and subjects received electrical stimulations on the plantar site of the foot at three stimulation intensities to evoke a nociceptive withdrawal reflex. Electromyogram and EEG were recorded for analysis. RESULTS: Patients with DSPN had higher perception (P < 0.001) and reflex (P = 0.012) thresholds. Fewer patients completed the recording session compared with healthy controls (34/48 vs. 21/21; P = 0.004). Diabetic symmetrical polyneuropathy reduced the odds ratio of a successful elicited nociceptive withdrawal reflex (odds ratio = 0.045; P = 0.014). Diabetic symmetrical polyneuropathy changed the evoked potentials (F = 2.86; P = 0.025), and post hoc test revealed reduction of amplitude (-3.72 mV; P = 0.021) and prolonged latencies (15.1 ms; P = 0.013) of the N1 peak. CONCLUSIONS: The study revealed that patients with type 1 diabetes and DSPN have significantly changed spinal and supraspinal processing of the somatosensory input. This implies that DSPN induces widespread differences in the central nervous system processing of afferent A-δ and A-ß fiber input. These differences in processing may potentially lead to identification of subgroups with different stages of small fiber neuropathy and ultimately differentiated treatments.

The eight cervical nerve and its role in tinnitus.

INTRODUCTION: The eight cervical nerve might be a source of input to the auditory system. OBJECTIVES: The object was to assess the efficacy of infiltration of the eight cervical nerve root for treating tinnitus patients and to find indicators for a successful result. DESIGN: Retrospective cohort study. Subjects were 79 tinnitus patients visiting our clinic in a three-year period and who were treated with infiltration of the eight cervical nerve root. RESULTS: Twenty-six percent of the tinnitus patients had a reduction of their tinnitus following an infiltration of the eight cervical nerve root. Most of the successfully treated patients rated the effect of therapy as a moderate reduction of 25% to 50%. Fifty percent of the successful treated patients still had benefit at 6.6 months. In 5% of the patients, their tinnitus was aggravated after the infiltration of the eight cervical nerve roots. Patients with a hearing loss at 500 Hz that exceed the hearing loss at 2 kHZ responded the most to infiltration of the eight cervical nerve. CONCLUSION: Infiltration of the eight cervical nerve root reduced the intensity of tinnitus in 26% of the cohort of 79 tinnitus patients with a moderate to good effect. This therapy for tinnitus patients' needs to be considered, especially in those with a hearing loss at 500 Hz that exceed the hearing loss at 2 kHZ.

Upper Cervical Nerves Can Induce Tinnitus.

INTRODUCTION: Treating cervical spine disorders can result in a reduction of tinnitus. OBJECTIVES: The object of the study was to ascertain the benefit of therapy of the third and fourth cervical nerves in reducing tinnitus and to assess parameters indicating a long-term relief. DESIGN: Subjects were 37 tinnitus patients who were treated with infiltration of the third and fourth cervical nerves. Clinical data form these patients were reviewed retrospectively. An independent perceiver evaluated the long-term effect of the therapy by telephone interview. RESULTS: In a group of tinnitus patients, 19% of the patients reported less tinnitus after therapy of the third and fourth cervical nerves. Most of the patients had a moderate reduction of 25% to 50%. At 3.8 months, 50% of the successful treated patients still had a positive effect. No adverse events of the procedure were observed. The combination of an evident anterior spur at the third cervical vertebrae together with less hearing at 2 kHz indicate patients who responded the best to therapy of the third and fourth cervical nerves. CONCLUSIONS: Treating cervical spine disorders can reduce tinnitus. In a group of tinnitus patients, 19% of the patients had less tinnitus after therapy of the C3 and C4. Screening of tinnitus patients is needed for the proper selection of the ones who could benefit from a somatic approach. In our study, the combination of an evident anterior spur at the third cervical vertebrae together with less hearing at 2 kHz indicate patients who responded the best following therapy of the C3 and C4.

Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain.

BACKGROUND: Stimulation of the occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the 'trigeminocervical complex' (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in the spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad. METHODS: Adult male Wistar rats were used. Neuronal recordings were obtained in laminae II-IV in the TCC in control, sham and infraorbital chronic constriction injury (CCI-IoN) animals. The GON was isolated and electrically stimulated. Responses to the stimulation of vibrissae by brief air pulses were analyzed before and after GON stimulation. In order to understand the role of the neurotransmitters involved, specific receptor blockers of NMDA (AP-5), GABAA (bicuculline, Bic) and Glycine (strychnine, Str) were applied locally. RESULTS: GON stimulation produced a facilitation of the response to light facial mechanical stimuli in controls, and an inhibition in CCI-IoN cases. AP-5 reduced responses to GON and vibrissal stimulation and blocked the facilitation of GON on vibrissal responses found in controls. The application of Bic or Str significantly reduced the facilitatory effect of GON stimulation on the response to vibrissal stimulation in controls. However, the opposite effect was found when GABAergic or Glycinergic transmission was prevented in CCI-IoN cases. CONCLUSIONS: GON stimulation modulates the responses of TCC neurons to light mechanical input from the face in opposite directions in controls and under CCI-IoN. This modulation is mediated by GABAergic and Glycinergic mechanisms. These results will help to elucidate the neural mechanisms underlying the effectiveness of nerve stimulation in controlling painful craniofacial disorders, and may be instrumental in identifying new therapeutic targets for their prevention and treatment.

The Delayed-Onset Mechanical Pain Behavior Induced by Infant Peripheral Nerve Injury Is Accompanied by Sympathetic Sprouting in the Dorsal Root Ganglion.

BACKGROUND: Sympathetic sprouting in the dorsal root ganglion (DRG) following nerve injuries had been proved to induce adult neuropathic pain. However, it is unclear whether the abnormal sprouting occurs in infant nerve injury. METHODS: L5 spinal nerve ligation (SNL) or sham surgery was performed on adult rats and 10-day-old pups, and mechanical thresholds and heat hyperalgesia were analyzed on 3, 7, 14, 28, and 56 postoperative days. Tyrosine hydroxylase-labeled sympathetic fibers were observed at each time point, and 2 neurotrophin receptors (p75NTR and TrkA) were identified to explore the mechanisms of sympathetic sprouting. RESULTS: Adult rats rapidly developed mechanical and heat hyperalgesia from postoperative day 3, with concurrent sympathetic sprouting in DRG. In contrast, the pup rats did not show a significantly lower mechanical threshold until postoperative day 28, at which time the sympathetic sprouting became evident in the DRG. No heat hyperalgesia was presented in pup rats at any time point. There was a late expression of glial p75NTR in DRG of pups from postoperative day 28, which was parallel to the occurrence of sympathetic sprouting. The expression of TrkA did not show such a postoperative syncing change. CONCLUSION: The delayed-onset mechanical allodynia in the infant nerve lesion was accompanied with parallel sympathetic sprouting in DRG. The late parallel expression of glial p75NTR injury may play an essential role in this process, which provides novel insight into the treatment of delayed adolescent neuropathic pain.

Localized sympathectomy reduces peripheral nerve regeneration and pain behaviors in 2 rat neuropathic pain models.

Previous studies have shown that the peripheral nerve regeneration process is linked to pain in several neuropathic pain models. Other studies show that sympathetic blockade may relieve pain in some pain models and clinical conditions. This study examined reduction in peripheral nerve regeneration as one possible mechanism for relief of neuropathic pain by sympathetic blockade. A "microsympathectomy," consisting of cutting the gray rami containing sympathetic postganglionic axons where they enter the L4 and L5 spinal nerves, reduced mechanical hypersensitivity in 2 different rat neuropathic pain models. In the spinal nerve ligation model, in which some functional regeneration and reinnervation of the ligated spinal nerve can be observed, microsympathectomy reduced functional and anatomical measures of regeneration as well as expression of growth-associated protein 43 (GAP43), a regeneration-related protein. In the spared nerve injury model, in which functional reinnervation is not possible and the futile regeneration process results in formation of a neuroma, microsympathectomy reduced neuroma formation and GAP43 expression. In both models, microsympathectomy reduced macrophage density in the sensory ganglia and peripheral nerve. This corroborates previous work showing that sympathetic nerves may locally affect immune function. The results further highlight the challenge of improving pain in neuropathic conditions without inhibiting peripheral nerve regeneration that might otherwise be possible and desired.

Central motor conduction time reveals upper motor neuron involvement masked by lower motor neuron impairment in a significant portion of patients with amyotrophic lateral sclerosis.

OBJECTIVE: We retrospectively investigated the utility of the central motor conduction time (CMCT) in detecting upper motor neuron (UMN) involvements in patients with amyotrophic lateral sclerosis (ALS). METHODS: Fifty-two ALS patients and 12 disease control patients participated in this study. Surface electromyograms were recorded from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. We stimulated the motor cortex, brainstem, and spinal nerve using transcranial magnetic stimulation (TMS) in order to measure the cortical, brainstem, and spinal latencies. We divided the ALS patients into 2 subgroups (with UMN impairment vs. without UMN impairment) and calculated the rates of abnormal CMCT prolongation judged by their comparison with the normal ranges obtained by the measurement in the control patients. RESULTS: The CMCTs in the FDI and TA were abnormally prolonged in over 40% of the ALS patients with UMN impairment and in nearly 30% of those without UMN impairment. CONCLUSIONS: CMCT shows UMN dysfunction in ALS patients without clinical UMN impairment. SIGNIFICANCE: TMS still has diagnostic utility in a significant portion of ALS patients.

Neurectomy of C2 for the Treatment of Occipital Neuralgia: Case Report

Occipital neuralgia (ON) is an uncommon cause of headache, and it is characterized by a stabbing paroxysmal pain that radiates to the occipital region. The present study includes a review of the literature and a case report. The etiology of this pathology can vary from traumas, infections, compressions of nerves or vertebrae, skull base surgeries, to degenerative changes and congenital anomalies. However, most of the time, the etiology is considered idiopathic. The diagnosis is essentially clinical. However, it is crucial that other types of primary headache are excluded. The treatment for ON may be based on nerve blocks, medications or surgeries. Neurectomy of the second spinal nerve is among the surgical techniques available.

Lumbar Degenerative Disease Part 1: Anatomy and Pathophysiology of Intervertebral Discogenic Pain and Radiofrequency Ablation of Basivertebral and Sinuvertebral Nerve Treatment for Chronic Discogenic Back Pain: A Prospective Case Series and Review of Literature.

Degenerative disc disease is a leading cause of chronic back pain in the aging population in the world. Sinuvertebral nerve and basivertebral nerve are postulated to be associated with the pain pathway as a result of neurotization. Our goal is to perform a prospective study using radiofrequency ablation on sinuvertebral nerve and basivertebral nerve; evaluating its short and long term effect on pain score, disability score and patients' outcome. A review in literature is done on the pathoanatomy, pathophysiology and pain generation pathway in degenerative disc disease and chronic back pain. 30 patients with 38 levels of intervertebral disc presented with discogenic back pain with bulging degenerative intervertebral disc or spinal stenosis underwent Uniportal Full Endoscopic Radiofrequency Ablation application through either Transforaminal or Interlaminar Endoscopic Approaches. Their preoperative characteristics are recorded and prospective data was collected for Visualized Analogue Scale, Oswestry Disability Index and MacNab Criteria for pain were evaluated. There was statistically significant Visual Analogue Scale improvement from preoperative state at post-operative 1wk, 6 months and final follow up were 4.4 ± 1.0, 5.5 ± 1.2 and 5.7 ± 1.3, respectively, p < 0.0001. Oswestery Disability Index improvement from preoperative state at 1week, 6 months and final follow up were 45.8 ± 8.7, 50.4 ± 8.2 and 52.7 ± 10.3, p < 0.0001. MacNab criteria showed excellent outcomes in 17 cases, good outcomes in 11 cases and fair outcomes in 2 cases Sinuvertebral Nerve and Basivertebral Nerve Radiofrequency Ablation is effective in improving the patients' pain, disability status and patient outcome in our study.

The effect of vitamin D replacement on spinal inhibitory pathways in women with chronic widespread pain.

Vitamin D replacement helps in pain reduction in patients with chronic widespread pain (CWP). But the current literature lack studies that investigate its mechanism. Cutaneous silent period (CSP) is the electrophysiologic analog of the spinal inhibitory pathways and an objective method to document their involvement. This study aims to show if vitamin D replacement has an effect on the spinal inhibitory pathways through CSP parameters. Female patients who have CWP with vitamin D deficiency were included. Patients received an 8-week replacement therapy of vitamin D. Patients' pain were evaluated using the visual analog scale (VAS) and Leeds assessment of neuropathic symptoms and signs pain scale (LANSS). Quality of life with Nottingham Health Profile (NHP) and CSP parameters were also recorded before and after treatment. A total of 51 patients were included in the final analyses. The mean age of the patients was 44.3 ± 12.7 (minimum 18-maximum 65). Mean symptom duration was 13.1 ± 6.7 (minimum3-maximum 24) months. Patients' mean BMI was 21.6 ± 3.9 (minimum 18.0 maximum 29.1). Patients' median VAS and LANSS scores decreased significantly (p < 0.01) and NHP scores improved significantly in all subsets (p < 0.01). Vitamin D replacement did not significantly change CSP latency and duration (p = 0.06 and p = 0.12).Vitamin D replacement does not seem to work via modifying the spinal inhibitory pathways that are involved in the formation of the cutaneous silent period. This is the first study to objectively investigate the effect of vitamin D replacement on central sensitization mechanisms.

Temporal gene expression changes after acute and delayed ventral root avulsion-reimplantation.

BACKGROUND: In a model of injured spinal motor neurons where the avulsed spinal nerve is surgically reimplanted, useful regrowth of the injured nerve follows, both in animal experiments and clinical cases. This has led to surgical reimplantation strategies with subsequent partial functional motoric recovery. Still, the ideal time point for successful regeneration after reimplantation and the specific genetic profile of this time point is not known. OBJECTIVE: To explore the temporal gene expression of the whole genome in the ventral spinal cord after reimplantation at different time points after avulsion. METHODS: Totally 18 adult rats were subjected to avulsion of the left L5 root only (N = 3), avulsion followed by acute spinal reimplantation (N = 3), avulsion followed by 24 h (N = 3) or 48 h (N = 3) delayed reimplantation. Animals were allowed to survive 24 h after their respective surgery whereafter the ventral quadrant of the spinal cord at the operated side was harvested, processed for and analysed with Affymetrix Rat Gene ST 1.0 array followed by statistical analysis of gene expression patternsResults:Specific gene expression patterns were found at different time points after avulsion and reimplantation. Over all, early reimplantation seemed to diminish inflammatory response and support gene regulation related to neuronal activity compared to avulsion only or delayed reimplantation. In addition did gene activity after avulsion-reimplantation correspond to regeneration-associated genes typical for regeneration in the peripheral nervous system. CONCLUSIONS: Our study reveal that genetic profiling after this kind of injury is possible, that specific and distinct expression patterns can be found with early reimplantation being favourable over late and that regenerative activity in this kind of injury bears hallmark typical for peripheral nerve regeneration. These findings can be useful in elucidating specific genetic expression typical for successful nerve regeneration, hopefully not only in this specific model but in the nervous system in general.