Impaired Sensory Function Research Articles

The neuroprotective effect of N-acetylcysteine in spinal cord-injured rats.

Spinal cord injury (SCI) is an important cause of impairment of sensory and motor nerve function. It has been shown that free-radical species play an important role in the pathogenesis of acute tissue trauma after SCI. There are no proven pharmacological therapies that provide neuroprotection and stimulate axonal growth after trauma. The aim of this study was to investigate the neuroprotective effect of N-acetylcysteine (NAC) on the regeneration of spinal cord injuries in rats. A total of 20 male Wistar C rats were subjected to SCI and divided into control and experimental groups. In the control group (n = 10) trepanation and SCI by means of a pressure impactor was performed without any therapy. In the study group (n = 10), 1 dose of NAC was applied intraperitoneally (150 mg/kg b.w.) immediately after SCI, and another one after 24 h. The functional outcome on the Basso-Beattie-Bresnahan (BBB) scale and sciatic functional index (SFI) and morphological features of regeneration were analyzed during a 12-week follow-up. The spinal cords and brains were collected 12 weeks after SCI for histopathological and immunohistochemical analyses. The rats treated with NAC presented some improvement in locomotor activity and spinal cord morphology when compared to the control group. Namely, the hind paw angle of rotation was significantly lower in the NAC group than in the control group. No differences were observed between the control and study groups in terms of interlimb coordination. The area of the main lesion was only slightly decreased in the NAC group as compared to the control group. The length of lesions in the injured spinal cord in the NAC group was diminished in comparison to the control group. The number of FG-positive cells was higher in the NAC group than in the control group. The study showed that the neuroprotective activity of NAC had limited positive influence on the regeneration of the isolated SCI in rats.

Association of riluzole and dantrolene improves significant recovery after acute spinal cord injury in rats

Background ContextDamage to the spinal cord can result in irreversible impairment or complete loss of motor, sensory, and autonomic functions. Riluzole and dantrolene have been shown to provide neuroprotection by reducing neuronal apoptosis after brain and spinal cord injury (SCI) in several animal models of neurologic disorders. As these drugs protect the injured spinal cord through different mechanisms, we investigated the cumulative effects of riluzole and dantrolene. PurposeThis study aimed to investigate the neuroprotective efficacy of the combined administration of riluzole and dantrolene in experimental thoracic SCI. Study DesignTwenty-nine Wistar rats were laminectomized at T12 and divided in five groups. Rats in GI (n=6) underwent laminectomy alone and were treated with placebo. Rats in GII (n=6) underwent laminectomy followed by SCI and were treated with placebo. Rats in GIII (n=5) underwent laminectomy followed by SCI and were treated with riluzole and placebo 15 minutes and 1 hour after laminectomy, respectively. Rats in GIV (n=6) underwent laminectomy followed by SCI and were treated with placebo and dantrolene 15 minutes and 1 hour after laminectomy, respectively. Rats in GV (n=6) underwent laminectomy followed by SCI and were treated with riluzole and dantrolene 15 minutes and 1 hour after laminectomy, respectively. A compressive trauma was performed to induce SCI. MethodsBehavioral testing of hind limb function was performed using the Basso Beattie Bresnahan locomotor rating scale, which revealed significant recovery in the group treated with the association of riluzole and dantrolene compared with other groups. After euthanasia, the spinal cord was evaluated using light microscopy and immunochemistry with anti-NeuN and transferase dUTP nick-end-labeling (TUNEL) staining. ResultsAnimals treated with the association of riluzole and dantrolene showed a larger number of NeuN-positive neurons adjacent to the epicenter of injury (p≤.05). Furthermore, the TUNEL staining was similar between animals treated with riluzole and dantrolene and those that did not receive spinal cord trauma (p>.05). ConclusionsThese results showed that riluzole and dantrolene have a synergistic effect in neuroprotection after traumatic SCI by decreasing apoptotic cell death.

Chd7 Collaborates with Sox2 to Regulate Activation of Oligodendrocyte Precursor Cells after Spinal Cord Injury.

Oligodendrocyte precursor cells (OPCs) act as a reservoir of new oligodendrocytes (OLs) in homeostatic and pathological conditions. OPCs are activated in response to injury to generate myelinating OLs, but the underlying mechanisms remain poorly understood. Here, we show that chromodomain helicase DNA binding protein 7 (Chd7) regulates OPC activation after spinal cord injury (SCI). Chd7 is expressed in OPCs in the adult spinal cord and its expression is upregulated with a concomitant increase in Sox2 expression after SCI. OPC-specific ablation of Chd7 in injured mice leads to reduced OPC proliferation, the loss of OPC identity, and impaired OPC differentiation. Ablation of Chd7 or Sox2 in cultured OPCs shows similar phenotypes to those observed in Chd7 knock-out mice. Chd7 and Sox2 form a complex in OPCs and bind to the promoters or enhancers of the regulator of cell cycle (Rgcc) and protein kinase Cθ (PKCθ) genes, thereby inducing their expression. The expression of Rgcc and PKCθ is reduced in the OPCs of the injured Chd7 knock-out mice. In cultured OPCs, overexpression and knock-down of Rgcc or PKCθ promote and suppress OPC proliferation, respectively. Furthermore, overexpression of both Rgcc and PKCθ rescues the Chd7 deletion phenotypes. Chd7 is thus a key regulator of OPC activation, in which it cooperates with Sox2 and acts via direct induction of Rgcc and PKCθ expression.SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to oligodendrocyte (OL) loss and demyelination, along with neuronal death, resulting in impairment of motor or sensory functions. Oligodendrocyte precursor cells (OPCs) activated in response to injury are potential sources of OL replacement and are thought to contribute to remyelination and functional recovery after SCI. However, the molecular mechanisms underlying OPC activation, especially its epigenetic regulation, remain largely unclear. We demonstrate here that the chromatin remodeler chromodomain helicase DNA binding protein 7 (Chd7) regulates the proliferation and identity of OPCs after SCI. We have further identified regulator of cell cycle (Rgcc) and protein kinase Cθ (PKCθ) as novel targets of Chd7 for OPC activation.

Nerve injuries of the upper extremity and hand.

A nerve injury has a profound impact on the patient’s daily life due to the impaired sensory and motor function, impaired dexterity, sensitivity to cold as well as eventual pain problems.To perform an appropriate treatment of nerve injuries, a correct diagnosis must be made, where the injury is properly classified, leading to an optimal surgical approach and technique, where timing of surgery is also important for the outcome.Knowledge about the nerve regeneration process, where delicate processes occur in neurons, non-neuronal cells (i.e. Schwann cells) and other cells in the peripheral as well as the central nervous systems, is crucial for the treating surgeon.The surgical decision to perform nerve repair and/or reconstruction depends on the type of injury, the condition of the wound as well as the vascularity of the wound.To reconnect injured nerve ends, various techniques can be used, which include both epineurial and fascicular nerve repair, and if a nerve defect is caused by the injury, a nerve reconstruction procedure has to be performed, including bridging the defect using nerve-grafts or nerve transfer techniques.The patients must be evaluated properly and regularly after the surgical procedure and appropriate rehabilitation programmes are useful to improve the final outcome.Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160071. Originally published online at www.efortopenreviews.org

Upper limb impairment is associated with use of assistive devices and unemployment in multiple sclerosis

BackgroundIndividuals with multiple sclerosis (MS) frequently suffer from impaired sensory function, reduced strength and tremor in the upper limbs, which may interfere with upper limb function. However, upper limb impairment in MS is under-recognized and understudied. We aimed to evaluate the prevalence of upper limb impairment in a large sample of persons with MS; the association between upper limb function and employment status in MS; and the frequency of use of assistive devices aimed at addressing upper limb impairments. MethodsWe surveyed participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding upper limb function using the ABILHAND questionnaire, and asked about use of assistive devices intended to improve the performance on upper limb activities. We evaluated the association between ABILHAND scores and current employment status using multivariable logistic regression analysis, and the association between ABILHAND scores and the use of an assistive device. ResultsOf 7463 eligible respondents, 5846 (78.3%) were female and mean (SD) age of 57.4 (10.2) years. The median (IQR) score on the ABILHAND was 45 (39–46). Higher levels of disability, as measured by the PDDS, correlated moderately with lower (worse) scores on the ABILHAND (r=−0.50; 95%CI: −0.48, −0.52). Over half of participants reported that they possessed an assistive device to aid upper limb function (3914, 56.0%). Older age, female sex, greater ambulatory disability, higher levels of fatigue, sensory impairment, spasticity and cognitive impairment, and visiting an occupational therapist were independently associated with increased odds of using an assistive device. After accounting for disability, perceived cognitive impairment, and fatigue, impaired upper limb function was associated with decreased odds of being employed (OR/1 point rise in ABILHAND 0.97; 95%CI: 0.96, 0.98). ConclusionsUpper limb impairment is common in older MS patients, and adversely affects the ability to perform many common daily activities.

Comparison of Gait Speed and Peripheral Nerve Function Between Chronic Kidney Disease Patients With and Without Diabetes.

ObjectiveTo compare overall physical function, including gait speed and peripheral nerve function, between diabetic chronic kidney disease (CKD) patients and nondiabetic CKD patients and to investigate the association between gait speed and peripheral nerve function in CKD patients.MethodsSixty adult CKD patients (35 with and 25 without diabetes), who received maintenance hemodialysis (HD), were included in this study. Demographic data, past medical history, current medical condition and functional data—usual gait speed, vibration perception threshold for the index finger (VPT-F) and the great toe (VPT-T), activity of daily living (ADL) difficulty, and peripheral neuropathy (PN) along with the degree of its severity—were collected and compared between the two groups. Correlations between the severity of PN and the impairment of other functions were identified.ResultsDiabetic CKD patients showed significantly slower gait speed (p=0.029), impaired sensory function (VPT-F, p=0.011; VPT-T, p=0.023), and more frequent and severe PN (number of PN, p<0.001; severity of PN, p<0.001) as compared to those without diabetes. Usual gait speed had a significant negative correlation with the severity of PN (rho=−0.249, p=0.013). By contrast, VPT-F (rho=0.286, p=0.014) and VPT-T (rho=0.332, p=0.035) were positively correlated with the severity of PN. ADL difficulty was comparatively more frequent in the patients with more severe PN (p=0.031).ConclusionIn CKD patients with maintenance HD, their gait speed, sensory functions, and peripheral nerve functions were all significantly impaired when they have diabetes, and the severity of PN was negatively correlated with their gait speed, sensory function, and ADL function. Adverse effects of diabetes impacted physical performance of CKD patients. The physical disability of those patients might be attributable to PN and its severity.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy 101—Pitfalls and Pearls of Diagnosis and Treatment

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which is caused by demyelination of the peripheral nerves, is characterized by progressive weakness and impaired sensory function in the arms and legs. CIDP is a treatable condition in which early diagnosis is crucial to limit chronic disability. CIDP can mimic other neuropathies and it is important to identify these in order to ensure prompt treatment. Patients with other causes of neuropathy should be suspected of having CIDP if there is rapid progress or proximal weakness. Intravenous immunoglobulin (IVIG), corticosteroids, and plasma exchange are first-line therapies. The IVIG CIDP Efficacy (ICE) trial, the largest trial reported of any CIDP treatment, demonstrated that IVIG therapy reduced disability and functional impairment, as well as improved quality of life. Autoantibodies against membrane proteins of the peripheral nerve axons or the myelin sheath have been reported recently, and an improved understanding of antibody responses in CIDP may enable the development of future targeted therapeutic interventions.

Impaired glyoxalase activity is associated with reduced expression of neurotrophic factors and pro-inflammatory processes in diabetic skin cells.

Patients suffering from type II diabetes develop several skin manifestations including cutaneous infections, diabetic dermopathy, diabetic bullae and acanthosis nigricans. Diabetic micro- and macroangiopathy as well as diabetic neuropathy are believed to play a crucial role in the development of diabetic skin disorders. A reduced cutaneous nerve fibre density was reported in diabetic subjects, which subsequently leads to impaired sensory nerve functions. Using an innervated skin model, we investigated the impact of human diabetic dermal fibroblasts and keratinocytes on porcine sensory neurons. Diabetic skin cells showed a reduced capacity to induce neurite outgrowth due to a decreased support with neurotrophic factors, such as NGF. Furthermore, diabetic keratinocytes displayed insulin resistance and increased expression of pro-inflammatory cytokines demonstrating the persistent effect of diabetes mellitus on human skin cells. Dysregulations were related to a significantly reduced glyoxalase enzyme activity in diabetic keratinocytes as experimentally reduced glyoxalase activity mimicked the increase in pro-inflammatory cytokine expression and reduction in NGF. Our results demonstrate an impaired crosstalk of diabetic skin cells and sensory neurons favouring hypo-innervation. We suggest that reduced methylglyoxal detoxification contributes to an impaired neurocutaneous interaction in diabetic skin.

Postural control among normal population of different age groups

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Postural control continues to change in later stages of life. Age-related changes may occur within or between sub-systems involved in postural control. It is thought clinically that these changes are important as they often result in falls &amp;amp; injury. The aim of the work was to compare the balance characteristics among different age groups using computerized dynamic posturography to provide clinicians with normal references&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Inclusion criteria were study group consisted of (30) normal healthy individuals, age range 16-79 years, with neither hearing nor vestibular complaints. It was divided into 3 age groups, each group consisted of 10 patients. Group (A) young- 16-39 years, group (B) middle- 40-59 years and group (C) elderly- 60-79 years. Exclusion criteria were history of neuromuscular or neuroskeletal disease, symptoms of unsteadiness, dizziness or vertigo, symptoms of impaired sensory function, symptoms of arthritis or lower limb problem, symptoms of uncorrected visual problems, symptoms of postural hypotension or diabetes, medication intake such as sedatives, hypnotics, anxiolytics &amp;amp; antidepressants. All participants were subjected to full history taking, otologic examination, basic audiologic evaluation, computerized dynamic posturography which included sensory organization test, limits of stability and rhythmic weight shift&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;Sensory organization test: The elderly group (C) had lowest equilibrium score with eyes open, closed &amp;amp; with conflicted visual cues on swayed surface (condition 6) and also this group have lowest percentage of SOT strategy. There was a statistically significant difference among A &amp;amp; C groups when using sensory organization test strategy in all conditions. Limits of stability test: The elderly group has higher overall reaction time. There was statistically significant difference in all conditions of limits of stability as regards directional control. Rhythmic weight shift right and left test: There was a statistically significant difference between groups A &amp;amp; C in low &amp;amp; medium speed on on-axis velocity &amp;amp; directional control. Rhythmic weight shift front &amp;amp; back test: There was no statistically significant difference between all groups as regards on-axis velocity. There was highly statistically significant difference between all groups in all trials as regards directional control.&lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Postural instability occurs frequently in healthy elderly subjects. Sensory organization test is the most effective test to compare balance function among different age groups&lt;span lang="EN-IN"&gt;.&lt;/span&gt;&lt;/p&gt;

Features of peripheral nerve injuries in workers exposed to vibration: an analysis of 197 cases

Objective: To investigate the features of peripheral nerve injuries in workers exposed to vibration. Methods: A total of 197 male workers [median age: 34 years (21-50 years) ; median working years of vibration exposure: 7.3 years (1-20 years) ] engaged in grinding in an enterprise were enrolled. Their clinical data and electromyography results were analyzed to investigate the features of peripheral nerve impairment. Results: Of all workers, 96 (48.73%) had abnormal electromyography results. Of all workers, 88 (44.7%) had simple mild median nerve injury in the wrist, who accounted for 91.7% (88/96) of all workers with abnormal electromy-ography results. Six workers had ulnar nerve injury, superficial radial nerve injury, or/and superficial peroneal nerve injury and accounted for 6.3% of all workers with abnormal electromyography results. Of all workers, 88 had a reduced amplitude of median nerve sensory transduction, and 28 had slowed median nerve sensory transduction. A total of 46 workers were diagnosed with occupational hand-arm vibration disease and hospitalized for treatment. They were followed up for more than 4 months after leaving their jobs, and most of them showed improvements in neural electromyography results and returned to a normal state. Conclusion: Workers exposed to vibration have a high incidence rate of nerve injury in the hand, mainly sensory function impairment at the distal end of the median nerve, and all injuries are mild peripheral nerve injuries. After leaving the vibration job and being treated, most workers can achieve improvements and return to a normal state.

Functional Characterization of At-Level Hypersensitivity in Patients With Spinal Cord Injury.

At-level hypersensitivity after complete thoracic SCI is associated with neuropathic below-level pain if evoked by clinical sensory stimuli. QST, LEP, and electrically-induced axon reflex flare sizes did not indicate somatosensory deafferentation in SCIHs.

Oxaliplatin added to fluoropyrimidine for adjuvant treatment of colorectal cancer is associated with long-term impairment of peripheral nerve sensory function and quality of life

Background: Oxaliplatin-induced peripheral neuropathy (OIPN) of acute and chronic type is well known, but long-term chronic type OIPN and its impact on quality of life (QoL) has not been extensively studied. Clinical experience indicates that oxaliplatin tolerance might vary with climate.Material and methods: Patient-reported chronic type OIPN and QoL among patients treated with oxaliplatin added to a fluoropyrimidine (Folfox or Capox) in the adjuvant setting of colorectal cancer (CRC) were assessed in a single center cross-sectional study by using the EORTC QLQ-CIPN20 and QLQ-C30 questionnaires. Comparison was made to patients treated with a fluoropyrimidine (5-FU or capecitabine) alone during the same time period.Results: Of 161 patients being disease-free 1–8 years after stop of treatment and invited, 84% participated; 65 treated with oxaliplatin and 71 with a fluoropyrimidine alone. Mean cumulative oxaliplatin dose was 567 mg/m2 (55% of planned dose). Oxaliplatin-treated patients reported statistically and clinically significant worse sensory as well as motor scale scores, dominated by symptoms from the feet. Severe tingling and numbness in toes/feet was reported by 38% and 37%, respectively, by oxaliplatin-treated patients compared with 8% for both by fluoropyrimidine alone patients (p < 0.001). Subgroup analyses indicated no impact of gender, age, regimen, time since stop of treatment or cumulated oxaliplatin dose for severity of the chronic type OIPN. The oxaliplatin compared with the fluoropyrimidine group reported worse QoL scores throughout all domains, with statistically and clinically significant differences for role and social function, nausea/loss of appetite and financial problems.Conclusions: Oxaliplatin added to a fluoropyrimidine for adjuvant treatment of CRC in a country with subarctic climate is associated with long-term, seemingly chronic, sensory neuropathy and impairment of QoL. This should be taken into account in clinical decision making on oxaliplatin treatment in the adjuvant setting.

Ocean acidification affects fish spawning but not paternity at CO2 seeps.

Fish exhibit impaired sensory function and altered behaviour at levels of ocean acidification expected to occur owing to anthropogenic carbon dioxide emissions during this century. We provide the first evidence of the effects of ocean acidification on reproductive behaviour of fish in the wild. Satellite and sneaker male ocellated wrasse (Symphodus ocellatus) compete to fertilize eggs guarded by dominant nesting males. Key mating behaviours such as dominant male courtship and nest defence did not differ between sites with ambient versus elevated CO2 concentrations. Dominant males did, however, experience significantly lower rates of pair spawning at elevated CO2 levels. Despite the higher risk of sperm competition found at elevated CO2, we also found a trend of lower satellite and sneaker male paternity at elevated CO2 Given the importance of fish for food security and ecosystem stability, this study highlights the need for targeted research into the effects of rising CO2 levels on patterns of reproduction in wild fish.

Time-Dependent Discrepancies between Assessments of Sensory Function after Incomplete Cervical Spinal Cord Injury.

We recently demonstrated that the electrical perceptual threshold (EPT) examination reveals spared sensory function at lower spinal segments compared with the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we investigated whether discrepancies in sensory function detected by both sensory examinations change over time after SCI. Forty-five participants with acute (<1 year), chronic (≥1-10 years), and extended-chronic (>10 years) incomplete cervical SCI and 30 control subjects were tested on dermatomes C2-T4 bilaterally. EPT values were higher in subjects with acute (2.5 ± 0.8 mA), chronic (2.2 ± 0.7 mA), or extended-chronic (2.8 ± 1.1 mA) SCI compared with controls (1.0 ± 0.1 mA). The EPT examination detected sensory impairments in spinal segments above (2.3 ± 0.9) and below (4.2 ± 2.6) the level detected by the ISNCSCI sensory examination in participants with acute and chronic SCI, respectively. Notably, both examinations detected similar levels of spared sensory function in the extended-chronic phase of SCI (0.8 ± 0.5). A negative correlation was found between differences in EPT and ISNCSCI sensory levels and time post-injury. These observations indicate that discrepancies between EPT and ISNCSCI sensory scores are time-dependent, with the EPT revealing impaired sensory function above, below, or at the same spinal segment as the ISNCSCI examination. We propose that the EPT is a sensitive tool to assess changes in sensory function over time after incomplete cervical SCI.

Investigating the role of MRGPRC11 and capsaicin-sensitive afferent nerves in the anti-influenza effects exerted by SLIGRL-amide in murine airways.

BackgroundThe hexapeptide SLIGRL-amide activates protease-activated receptor-2 (PAR-2) and mas-related G protein-coupled receptor C11 (MRGPRC11), both of which are known to be expressed on populations of sensory nerves. SLIGRL-amide has recently been reported to inhibit influenza A (IAV) infection in mice independently of PAR-2 activation, however the explicit roles of MRGPRC11 and sensory nerves in this process are unknown. Thus, the principal aim of this study was to determine whether SLIGRL-amide-induced inhibition of influenza infection is mediated by MRGPRC11 and/or by capsaicin-sensitive sensory nerves.MethodsThe inhibitory effect of SLIGRL-amide on IAV infection observed in control mice in vivo was compared to effects produced in mice that did not express MRGPRC11 (mrgpr-cluster∆−/− mice) or had impaired sensory nerve function (induced by chronic pre-treatment with capsaicin). Complementary mechanistic studies using both in vivo and ex vivo approaches investigated whether the anti-IAV activity of SLIGRL-amide was (1) mimicked by either activators of MRGPRC11 (BAM8-22) or by activators (acute capsaicin) or selected mediators (substance P, CGRP) of sensory nerve function, or (2) suppressed by inhibitors of sensory nerve function (e.g. NK1 receptor antagonists).ResultsSLIGRL-amide and BAM8-22 dose-dependently inhibited IAV infection in mrgpr-cluster∆−/− mice that do not express MRGPRC11. In addition, SLIGRL-amide and BAM8-22 each inhibited IAV infection in capsaicin-pre-treated mice that lack functional sensory nerves. Furthermore, the anti-IAV activity of SLIGRL-amide was not mimicked by the sensory neuropeptides substance P or CGRP, nor blocked by either NK1 (L-703,606, RP67580) and CGRP receptor (CGRP8-37) antagonists. Direct stimulation of airway sensory nerves through acute exposure to the TRPV1 activator capsaicin also failed to mimic SLIGRL-amide-induced inhibition of IAV infectivity. The anti-IAV activity of SLIGRL-amide was mimicked by the purinoceptor agonist ATP, a direct activator of mucus secretion from airway epithelial cells. Additionally, both SLIGRL-amide and ATP stimulated mucus secretion and inhibited IAV infectivity in mouse isolated tracheal segments.ConclusionsSLIGRL-amide inhibits IAV infection independently of MRGPRC11 and independently of capsaicin-sensitive, neuropeptide-releasing sensory nerves, and its secretory action on epithelial cells warrants further investigation.

Sensitization of the Nociceptive System in Complex Regional Pain Syndrome.

BackgroundComplex regional pain syndrome type I (CRPS-I) is characterized by sensory, motor and autonomic abnormalities without electrophysiological evidence of a nerve lesion.ObjectiveAims were to investigate how sensory, autonomic and motor function change in the course of the disease.Methods19 CRPS-I patients (17 with acute, 2 with chronic CRPS, mean duration of disease 5.7±8.3, range 1–33 months) were examined with questionnaires (LANSS, NPS, MPI, Quick DASH, multiple choice list of descriptors for sensory, motor, autonomic symptoms), motor and autonomic tests as well as quantitative sensory testing according to the German Research Network on Neuropathic Pain at two visits (baseline and 36±10.6, range 16–53 months later).ResultsCRPS-I patients had an improvement of sudomotor and vasomotor function, but still a great impairment of sensory and motor function upon follow-up. Although pain and mechanical detection improved upon follow-up, thermal and mechanical pain sensitivity increased, including the contralateral side. Increase in mechanical pain sensitivity and loss of mechanical detection were associated with presence of ongoing pain.ConclusionsThe results demonstrate that patients with CRPS-I show a sensitization of the nociceptive system in the course of the disease, for which ongoing pain seems to be the most important trigger. They further suggest that measured loss of function in CRPS-I is due to pain-induced hypoesthesia rather than a minimal nerve lesion. In conclusion, this article gives evidence for a pronociceptive pain modulation profile developing in the course of CRPS and thus helps to assess underlying mechanisms of CRPS that contribute to the maintenance of patients’ pain and disability.

Mesenchymal stem cells transplantation to treat spinal cord injury: from basic science to clinical trial

Spinal cord injury (SCI), which lead to sensory and motor function impairment, refers to traumatic injury to the spinal cord. The main pathophysiological changing process can be divided into two phases: the preliminary injury phase and the secondary injury phase. Organ dysfunction, tissue necrosis, sensory and motor function of irreversible lesions and even death can be led by SCI and the secondary injury phase. In order to prevent the secondary injury and repair the injured central nerve system, medication, surgery, biomaterials transplantation and autologous peripheral nerve transplantation have been widely studied. However, these strategies can only reach a certain level of symptoms relieve and neural restoration, which cannot reach clinical satisfaction. Therefore, SCI has been treated as a global difficult and attractive topic. Since stem cells have the potential ability to promote neurons regeneration and/or even differentiate into neural like cells, they may also have anti-inflammatory, anti-apoptotic, anti-oxidative stress, and promote secretion of trophic factors and vascularization, they brought new hope for SCI patients. Mesenchymal stem cells (MSCs) have attracted many researchers' attention for their multi characteristics including widely distribution, strong differentiation potential, easily isolating and storing and ethics avoiding. It has been proved that MSCs are effective for repairing SCI in vivo and vitro. In the latest 3 years, with the consummation of several clinical trials, a good prospect have been showed in the translation of MSCs transplantation into clinic. MSCs have been proved to have a significant prospect for clinical translation. At the same time, more specific issues were also raised. Thus, based on the latest 3 years clinical research and the author team's latest experimental results, we reviewed the MSCs on treating SCI from basic science to clinical trial and discussed its future development.

The role of postsynaptic density proteins in neural degeneration and regeneration

The structure, function and plasticity of excitatory glutamatergic synapses in the brain are significantly altered by neurodevelopmental and neurodegenerative disorders (Grabrucker et al., 2011; Fourie et al., 2014; Musardo et al., 2014; Lee et al., 2015), resulting in impairments in cognition, learning, memory, motor and sensory function. Reversing these synaptic deficits is a major challenge for neuroscience, and significant research has focussed on glutamate receptors as therapeutic targets but human trials have shown little success. Recently, attention has turned to proteins localized to the postsynaptic density (PSD) of excitatory synapses, as these proteins control the trafficking and targeting of glutamate receptors at synapses. Not surprisingly, PSD proteins have been shown to be altered in human and rodent models of neurological disorders, suggesting changes in their expression during the disease process (Grabrucker et al., 2011; Fourie et al., 2014; Musardo et al., 2014; Mei et al., 2016). However, the sheer number of these proteins, each with unique splice variations and developmental expression profiles, raises the possibility that targeted expression of specific PSD protein subfamilies within defined time windows has significant therapeutic potential. Indeed rescue of normal social behaviour has recently been observed in adulthood in an autism rodent model by re-expression of SHANK3, which encodes a major PSD protein, yet rescue of anxiety and motor coordination deficits required SHANK3 re-expression earlier in development (Mei et al., 2016). Peptide disruption of PSD protein interactions with glutamate receptors is also showing promise to reduce excitotoxicity and ischaemic damage in stroke models (Zhou et al., 2015). Increasing our knowledge of the potential of these proteins in human neurons is the next important step, as this will be key to determining their true therapeutic potential for neuroregeneration.

Rootletin organizes the ciliary rootlet to achieve neuron sensory function in Drosophila.

Cilia are essential for cell signaling and sensory perception. In many cell types, a cytoskeletal structure called the ciliary rootlet links the cilium to the cell body. Previous studies indicated that rootlets support the long-term stability of some cilia. Here we report that Drosophila melanogaster Rootletin (Root), the sole orthologue of the mammalian paralogs Rootletin and C-Nap1, assembles into rootlets of diverse lengths among sensory neuron subtypes. Root mutant neurons lack rootlets and have dramatically impaired sensory function, resulting in behavior defects associated with mechanosensation and chemosensation. Root is required for cohesion of basal bodies, but the cilium structure appears normal in Root mutant neurons. We show, however, that normal rootlet assembly requires centrioles. The N terminus of Root contains a conserved domain and is essential for Root function in vivo. Ectopically expressed Root resides at the base of mother centrioles in spermatocytes and localizes asymmetrically to mother centrosomes in neuroblasts, both requiring Bld10, a basal body protein with varied functions.

Intrathecal Transplantation of Autologous Adherent Bone Marrow Cells Induces Functional Neurological Recovery in a Canine Model of Spinal Cord Injury.

Spinal cord injury (SCI) results in demyelination of surviving axons, loss of oligodendrocytes, and impairment of motor and sensory functions. We have developed a clinical strategy of cell therapy for SCI through the use of autologous bone marrow cells for transplantation to augment remyelination and enhance neurological repair. In a preclinical large mammalian model of SCI, experimental dogs were subjected to a clipping contusion of the spinal cord. Two weeks after the injury, GFP-labeled autologous minimally manipulated adherent bone marrow cells (ABMCs) were transplanted intrathecally to investigate the safety and efficacy of autologous ABMC therapy. The effects of ABMC transplantation in dogs with SCI were determined using functional neurological scoring, and the integration of ABMCs into the injured cords was determined using histopathological and immunohistochemical investigations and electron microscopic analyses of sections from control and transplanted spinal cords. Our data demonstrate the presence of GFP-labeled cells in the injured spinal cord for up to 16 weeks after transplantation in the subacute SCI stage. GFP-labeled cells homed to the site of injury and were detected around white matter tracts and surviving axons. ABMC therapy in the canine SCI model enhanced remyelination and augmented neural regeneration, resulting in improved neurological functions. Therefore, autologous ABMC therapy appears to be a safe and promising therapy for spinal cord injuries.