Spinal interleukin-6 contributes to central sensitisation and persistent pain hypersensitivity in a model of juvenile idiopathic arthritis

Pain is the most debilitating symptom in juvenile idiopathic arthritis. As pain correlates poorly to the extent of joint pathology, therapies that control joint inflammation are often inadequate as analgesics. We test the hypothesis that juvenile joint inflammation leads to sensitisation of nociceptive circuits in the central nervous system, which is maintained by cytokine expression in the spinal cord. Here, transient joint inflammation was induced in postnatal day (P)21 and P40 male Sprague-Dawley rats with a single intra-articular ankle injection of complete Freund’s adjuvant. Hindpaw mechanical pain sensitivity was assessed using von Frey hair and weight bearing tests. Spinal neuron activity was measured using in vivo extracellular recording and immunohistochemistry. Joint and spinal dorsal horn TNFα, IL1β and IL6 protein expression was quantified using western blotting. We observed greater mechanical hyperalgesia following joint inflammation in P21 compared to P40 rats, despite comparable duration of swelling and joint inflammatory cytokine levels. This is mirrored by spinal neuron hypersensitivity, which also outlasted the duration of active joint inflammation. The cytokine profile in the spinal cord differed at the two ages: prolonged upregulation of spinal IL6 was observed in P21, but not P40 rats. Finally, spinal application of anti-IL-6 antibody (30 ng) reduced the mechanical hyperalgesia and neuronal activation. Our results indicate that persistent upregulation of pro-inflammatory cytokines in the spinal dorsal horn is associated with neuronal sensitisation and mechanical hyperalgesia in juvenile rats, beyond the progress of joint pathology. In addition, we provide proof of concept that spinal IL6 is a key target for treating persistent pain in JIA.     

Short-term retention effect of rehabilitation using head position-based electrotactile feedback to the tongue: Influence of vestibular loss and old-age

Our objective was to evaluate whether the severity of vestibular loss and old-age (>65) affect a patient's ability to benefit from training using head-position based, tongue-placed electrotactile feedback. Seventy-one chronic dizzy patients, who had reached a plateau with their conventional rehabilitation, followed six 1-h training sessions during 4 consecutive days (once on days 1 and 4, twice on days 2 and 3). They presented bilateral vestibular areflexia (BVA), bilateral vestibular losses (BVL), unilateral vestibular areflexia or unilateral vestibular losses and were divided into two age-subgroups (≤65 and >65). Posturographic assessments were performed without the device, 4 h before and after the training. Patients were tested with eyes opened and eyes closed (EC) on static and dynamic (passively tilting) platforms. The studied posturographic scores improved significantly, especially under test conditions restricting either visual or somatosensory input. This 4-h retention effect was greater in older compared to younger patients and was proportional to the degree of vestibular loss, patients with increased vestibular losses showing greater improvements. In bilateral patients, who constantly fell under dynamic-EC condition at the baseline, the therapy effect was expressed by disappearance of falls in BVL and significant prolongation in time-to-fall in BVA subgroups.Globally, our data showed that short training with head-position based, tongue-placed electrotactile biofeedback improves balance in chronic vestibulopathic patients some 16.74% beyond that achieved with standard balance physiotherapy. Further studies with longer use of this biofeedback are needed to investigate whether this approach could have long-lasting retention effect on balance and quality of life.     

Age-based normative data for a computerized dynamic posturography system that uses a virtual visual surround environment

Background: Computerized dynamic posturography (CDP) is the gold standard to differentiate between sensory, motor, and central adaptive impairments to postural control.

Objective: To obtain normative values in healthy adults age 20–69 for a CDP system that uses a full-field dynamic visual surround. This is in contrast to the mechanically movable visual surround used in traditional CDP systems.

Methods: Fifty healthy adults divided into five age groups were tested during the three test protocols for CDP: sensory organization test (SOT), motor control test (MCT), and adaptation test (ADT). Outcomes were compared across age groups and to published normative CDP values. Repeatability was assessed in five different subjects (23–30 years old) on 2 days, 1 week apart.

Results: Most outcomes were comparable to published norms with notable differences in SOT condition 4 and ADT. SOT composite and conditions 4–6, all MCT translations, and ADT toes up showed moderate to good repeatability (r?=?0.60 to 0.99). Age group and gender differences were not substantial.

Conclusions: Some but not all CDP outcomes with a virtual visual environment were comparable to published norms. The differences are likely related to the virtual surround having a more compelling effect on balance even in conditions with a stationary surround.     

饮水负荷试验测定胃感觉的临床研究

目的　建立简便易行、非侵入性、符合胃肠生理的检测胃感觉阈值的诊断方法。方法用饮水负荷试验和电子恒压器法分别对 15例健康自愿者和 30例功能性消化不良患者的胃感知和不适阈值进行测定 ,以了解饮水负荷试验测定胃感觉阈值的敏感性、特异性、Kappa值、符合率 ,以及二者之间有无相关性。结果　与电子恒压器法相比较 ,饮水负荷试验测定胃感知阈值的敏感性为85 7% ,特异性为 93 5 % ,Kappa值为 0 82 ,二者的符合率为 91 1% ,两种方法所测得的结果也具有良好的相关性 (P <0 0 1)。饮水负荷试验测定胃不适阈值的敏感性为 81 8% ,特异性为 91 2 % ,Kappa值为 0 79,二者的符合率为 88 9% ,两种方法所测得的结果也具有良好的相关性 (P <0 0 1)。结论　与电子恒压器相比 ,饮水负荷试验测定胃感觉阈值具有较高的特异性、Kappa值和符合率 ,以及良好的相关性 ,可用于消化不良患者胃感觉功能临床辅助诊断和初筛检查 ,在基层医院有广泛的应用前景。     

Rectal compliance in females with obstructed defecation

PURPOSE: This study was designed to investigate whether rectal compliance is altered in females with obstructed defecation. METHODS: Eighty female patients with obstructed defecation and 60 control subjects were studied. Rectal compliance was measured with an infinitely compliant polyethylene bag. This bag was inserted in the rectum and inflated with air to selected pressure plateaus (range, 0–60 mmHg; cumulative steps of 2 mmHg with a duration of ten seconds) using a computer-controlled electromechanical barostat system. Volume changes at the levels of distending pressures were recorded. The distending pressures, needed to evoke first sensation of content in the rectum, earliest urge to defecate, and the maximum tolerable volume were noted. RESULTS: In all cases, the compliance curve had a characteristic triphasic (S-shaped) form. The mean compliance curve obtained from the patients was identical to that of the controls. However, the course of the compliance curve fell above the normal range (mean + 2 SD) in 14 patients. In ten (71 percent) of these patients, a large rectocele was seen at evacuation proctography. Such a rectocele was observed in only five patients (7.6 percent) with a normal compliance curve (P<0.001). Eighty percent of the controls experienced earliest urge to defecate during the second phase of the curve. In 75 percent of the patients, this occurred in the third phase. The mean pressure threshold for first sensation, earliest urge to defecate, and maximum tolerable volume were significantly higher in patients compared with control subjects. Ten of the patients experienced no sensation at all in the pressure range between 0 and 60 mmHg. CONCLUSION: In females with obstructed defection, the compliance of the rectal wall is normal.     

Sensory Innervation of the Female Human Umbilical Skin: Morphological Studies

Background: Sensory stimuli are conducted by several cutaneous sensory nerves and tactile corpuscles. The latter are specialized sensory organs that represent the starting point of many afferent sensory pathways. To date, our knowledge about the distribution of the sensory innervation in the umbilical skin of females is incomplete.

Aim of the study: To elucidate the morphology of the cutaneous innervation of the normal female umbilical skin.

Materials and methods: Biopsies of normal umbilical skin were obtained from female patients undergoing umbilical hernial repair. The specimens were processed for both immunohistological (antibodies against PGP9.5, pan-neuronal marker, and S-100 protein, marker of Schwann cells) and ultrastructural (transmission electron microscopy) examinations.

Results: The authors found abundant genital end-bulb-like structures, numerous epidermal and dermal Merkel cells, Meissner and Ruffini corpuscles, intraepidermal nerve terminals, and multiple free nerve endings surrounding the ducts and acini of the sweat glands.

Conclusions: The umbilical skin of females has abundant sensory innervation similar to that of the glans penis.     

Chronic effects of cannabis on sensory gating

Chronic cannabis use has been associated with neurocognitive deficits, alterations in brain structure and function, and with psychosis. This study investigated the effects of chronic cannabis use on P50 sensory-gating in regular users, and explored the association between sensory gating, cannabis use history and the development of psychotic-like symptoms. Twenty controls and 21 regular cannabis users completed a P50 paired-click (S1 and S2) paradigm with an inter-pair interval of 9 s. The groups were compared on P50 amplitude to S1 and S2, P50 ratio (S2/S1) and P50 difference score (S1–S2). While cannabis users overall did not differ from controls on P50 measures, prolonged duration of regular use was associated with greater impairment in sensory gating as indexed by both P50 ratio and difference scores (including after controlling for tobacco use). Long-term cannabis users were found to have worse sensory gating ratios and difference scores compared to short-term users and controls. P50 metrics did not correlate significantly with any measure of psychotic-like symptoms in cannabis users. These results suggest that prolonged exposure to cannabis results in impaired P50 sensory-gating in long-term cannabis users. While it is possible that these deficits may have pre-dated cannabis use and reflect a vulnerability to cannabis use, their association with increasing years of cannabis use suggests that this is not the case. Impaired P50 sensory-gating ratios have also been reported in patients with schizophrenia and may indicate a similar underlying pathology.     

An investigation of the effect of the lower extremity sensation on gait in children with cerebral palsy

BackgroundSensory disorders frequently accompany the motor disorders in children with cerebral palsy (CP).Research questionDo children with CP have sensory disturbances in their lower extremities? If there are sensory impairments, do these impairments affect gait?MethodsIn total, 45 children (18 females, 27 males) in an age range between 5 and 18 years were included in the study: 15 typically developing children, 15 unilaterally affected children with cerebral palsy, and 15 bilaterally affected children with cerebral palsy. They could walk independently at the levels of I or II according to the gross motor function classification. After the demographic data of the children were recorded, their tactile sense, vibration sense, two-point discrimination, and proprioception were evaluated, and the Edinburgh Visual Gait Score (EVGS) was used for gait assessment.ResultsFailures were discovered in lower extremity tactile (p = 0.001), two-point discrimination (p = 0.001), and proprioceptive senses of the children with CP (p = 0.001), and the loss of tactile sense was found to be related to gait disorders (p = 0.02, r = 0.41).SignificanceThere were deficiencies in the lower extremity senses, and deficiencies in the tactile sense negatively affected gait. Performing sensory assessments, which are considered to be fundamental for gait training in the rehabilitation of children with CP, and providing support for the lacking parameters in the intervention programs may create positive effects on gait.     

Effects of simulated peripheral visual field loss on the static postural control in young healthy adults

BackgroundIntegration of visual, vestibular, and proprioceptive sensations contributes to postural control. People with peripheral visual field loss have serious postural instability. However, the directional specificity of postural stability and sensory reweighting caused by gradual peripheral visual field loss remain unclear.Research questionWhat are the effects of peripheral visual field loss on static postural control?MethodsFifteen healthy young adults participated in this study. The participants were asked to stand quietly on a foam surface. Three conditions of virtual visual field loss (90°, 45°, and 15°) were provided by a head-mounted display, and ground reaction forces were collected using a force plate to calculate the displacements of the center of pressure (COP).ResultsThe root mean square (RMS), mean velocity, and 95% ellipse area of COP displacements in the horizontal plane increased, and RMS in the anteroposterior (AP) direction was unchanged under the smallest visual field condition compared to the largest one. The power spectrum density of COP displacements in the low-frequency band was decreased and that in the medium-frequency band was increased in the AP direction.SignificanceDuring quiet standing of young healthy adults with peripheral visual field loss, increased peripheral visual field loss resulted in lower postural stability. Postural stability in the AP direction was maintained contrary to the functional sensitivity hypothesis. Peripheral visual field loss reduced the weighting of the visual input and increased that of the vestibular input in the AP direction to maintain equilibrium.