Altered formalin-induced pain and Fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure

Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process

Cerebral cortex activation mapping upon electrical muscle stimulation by 32-channel time-domain functional near-infrared spectroscopy

The application of different EMS current thresholds on muscle activates not only the muscle but also peripheral sensory axons that send proprioceptive and pain signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was employed to map regional cortical activities under varied EMS current intensities applied on the right wrist extensor muscle. Eight healthy volunteers underwent four EMS at different current thresholds based on their individual maximal tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time courses of the absolute oxygenated and deoxygenated hemoglobin concentrations primarily over the bilateral sensorimotor cortical (SMC) regions were extrapolated, and cortical activation maps were determined by general linear model using the NIRS-SPM software. The stimulation-induced wrist extension paradigm significantly increased activation of the contralateral SMC region according to the EMS intensities, while the ipsilateral SMC region showed no significant changes. This could be due in part to a nociceptive response to the higher EMS current intensities and result also from increased sensorimotor integration in these cortical regions.

Effects of electrical muscle stimulation on oxygen consumption

Electrical muscle stimulation (EMS) devices are being marketed as weight/ fat loss devices throughout the world. Commercially available stimulators have the ability to evoke muscle contractions that may affect caloric expenditure while the device is being used. The aim of this study was to test the effects of two different EMS devices (Abtronic and Feminique) on oxygen consumption at rest. Subjects arrived for testing after an overnight fast, had the devices fitted, and then positioned supine with expired air measured to determine oxygen consumption. After a 10-minute acclimation period, oxygen consumption was measured for 20 minutes with the device switched off (resting) then 20 minutes with the device switched on (stimulated). There were no significant differences (p > 0.05) in oxygen consumption between the resting and stimulated periods with either the Abtronic (mean +/- SD; resting, 3.40 +/- 0.44; stimulated, 3.45 +/- 0.53 ml of O2[middle dot]kg-1[middle dot]min-1) or the Feminique (resting, 3.73 +/- 0.45; stimulated, 3.75 +/- 0.46 ml of O2[middle dot]kg-1[middle dot]min-1). In summary, the EMS devices tested had no effect on oxygen consumption during muscle stimulation.

Pedunculopontine nucleus deep brain stimulation produces sustained improvement in primary progressive freezing of gait

Objective: To assess the efficacy of bilateral pedunculopontine nucleus (PPN) deep brain stimulation (DBS) as a treatment for primary progressive freezing of gait (PPFG). ------ ----- Methods: A patient with PPFG underwent bilateral PPN-DBS and was followed clinically for over 14 months. ------ ----- Results: The PPFG patient exhibited a robust improvement in gait and posture following PPN-DBS. When PPN stimulation was deactivated, postural stability and gait skills declined to pre-DBS levels, and fluoro-2-deoxy-d-glucose positron emission tomography revealed hypoactive cerebellar and brainstem regions, which significantly normalised when PPN stimulation was reactivated. ------ ----- Conclusions: This case demonstrates that the advantages of PPN-DBS may not be limited to addressing freezing of gait (FOG) in idiopathic Parkinson's disease. The PPN may also be an effective DBS target to address other forms of central gait failure.

A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation

Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson’s disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients’ usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral.

Nutritional status in Parkinson's disease patients undergoing deep-brain stimulation surgery : a pilot study

People with Parkinson’s disease (PD) are at higher risk of malnutrition due to PD symptoms and pharmacotherapy side effects. Poorer outcomes are associated with higher amounts of weight loss (>5%) and lower levels of fat free mass. When pharmacotherapy is no longer effective for symptom control, deep-brain stimulation (DBS) surgery may be considered. People with PD scheduled for DBS surgery were recruited from a Brisbane neurological clinic (n=11 out of 16). The Scale for Outcomes of Parkinson’s disease –Autonomic (SCOPA-AUT), Modified Constipation Assessment Scale (MCAS), and a 3-day food diary were mailed to participants’ homes for completion prior to hospital admission. During admission, the Patient-Generated Subjective Global Assessment (PG-SGA), weight, height and body composition were assessed. Mean(±s.d.) PD duration from diagnosis and time since occurrence of PD symptoms was 9.0(±8.0) and 12(±8.8) years, respectively. Five participants reported unintentional weight loss (average loss of 15.6%). PD duration but not years since symptom onset significantly predicted PG-SGA scores (β=4.2, t(8)=2.7, p<.05). Both were positively correlated with PG-SGA score (r = .667, r=.587). On average, participants classified as well-nourished (SGA-A) (n=4) were younger, had shorter disease durations, lower PG-SGA scores, higher body mass (BMI) and fat free mass (FFMI) indices when compared to malnourished participants (SGA-B) (n=7). They also reported fewer non-motor symptoms on the SCOPA-AUT and MCAS. Three participants had previously received dietetic advice but not in relation to PD. These findings demonstrate that malnutrition remains unrecognised and untreated in this group despite unintentional weight loss and a high prevalence of malnutrition.

The stimulation of healing within a rat calvarial defect by mPCL–TCP/collagen scaffolds loaded with rhBMP-2

Bone morphogenetic proteins (BMPs) have been widely investigated for their clinical use in bone repair and it is known that a suitable carrier matrix to deliver them is essential for optimal bone regeneration within a specific defect site. Fused deposited modeling (FDM) allows for the fabrication of medical grade poly 3-caprolactone/tricalcium phosphate (mPCL–TCP) scaffolds with high reproducibility and tailor designed dimensions. Here we loaded FDM fabricated mPCL–TCP/collagen scaffolds with 5 mg recombinant human (rh)BMP-2 and evaluated bone healing within a rat calvarial critical-sized defect. Using a comprehensive approach, this study assessed the newly regenerated bone employing microcomputed tomography (mCT), histology/histomorphometry, and mechanical assessments. By 15 weeks, mPCL–TCP/collagen/rhBMP-2 defects exhibited complete healing of the calvarium whereas the non- BMP-2-loaded scaffolds showed significant less bone ingrowth, as confirmed by mCT. Histomorphometry revealed significantly increased bone healing amongst the rhBMP-2 groups compared to non-treated scaffolds at 4 and 15 weeks, although the % BV/TV did not indicate complete mineralisation of the entire defect site. Hence, our study confirms that it is important to combine microCt and histomorphometry to be able to study bone regeneration comprehensively in 3D. A significant up-regulation of the osteogenic proteins, type I collagen and osteocalcin, was evident at both time points in rhBMP-2 groups. Although mineral apposition rates at 15 weeks were statistically equivalent amongst treatment groups, microcompression and push-out strengths indicated superior bone quality at 15 weeks for defects treated with mPCL–TCP/collagen/rhBMP-2. Consistently over all modalities, the progression of healing was from empty defect < mPCL–TCP/collagen < mPCL–TCP/collagen/rhBMP-2, providing substantiating data to support the hypothesis that the release of rhBMP-2 from FDM-created mPCL–TCP/collagen scaffolds is a clinically relevant approach to repair and regenerate critically-sized craniofacial bone defects. Crown Copyright 2008 Published by Elsevier Ltd. All rights reserved.