Chronic pain syndromes encompass several clinical entities that frequently affect the individuals' emotional and cognitive behaviours which, in turn, can also alter pain perception. Additionally, both pain perception and motivational-affective behaviours change with increasing age. In order to evaluate the influence of age upon the interaction between chronic pain and affective/cognitive behaviours, 3-, 10- and 22-month-old rats with 1 month neuropathy (spared nerve injury, SNI model) were compared with age-matched sham-operated controls in the open field (OF; locomotor and exploratory behaviours), elevated plus-maze (EPM; anxiety-like behaviour), forced swimming (FST; depressive-like behaviour), working memory water maze (WM; spatial short-term memory), Morris water maze (MWM; spatial reference memory) and spatial reversal (behavioural flexibility) tests. Locomotor and exploratory activities decreased steadily with age and were further reduced by SNI. Aging was associated with increased anxiety-like behaviour, which was potentiated by SNI in both 3- and 22-month-old rats. The performance in the FST was affected by SNI but only in mid-aged animals. Cognitive performances in the MWM and spatial reversal tests deteriorated with age; however, the SNI lesion was only detrimental in the reversal task to mid-aged animals. Our data demonstrate that the influence of neuropathic pain on affective and cognitive behaviours is age dependent and varies with the behavioural domain that is tested. Importantly, mid-aged animals seem to be more susceptible to depression and cognitive deterioration associated to chronic pain than young and old groups.
Spinal cord injury (SCI) represents a significant health and social problem, and therefore it is vital to develop novel strategies that can specifically target it. In this context, the objective of the present work was to develop a new range of three-dimensional (3D) tubular structures aimed at inducing the regeneration within SCI sites. Up to six different 3D tubular structures were initially developed by rapid prototyping: 3D bioplotting-based on a biodegradable blend of starch. These structures were then further complemented by injecting Gellan Gum, a polysaccharide-based hydrogel, in the central area of structures. The mechanical properties of these structures were assessed using dynamic mechanical analysis, under both dry and wet conditions, and their morphologies/porosities were analyzed using micro-computed tomography and scanning electron microscopy. Biological evaluation was carried out to determine their cytotoxicity, using both minimum essential medium (MEM) extraction and MTS tests, as well as by encapsulation of an oligodendrocyte-like cell (M03-13 cell line) within the hydrogel phase. The histomorphometric analysis showed a fully interconnected network of pores with porosity ranging from 70% to 85%. Scaffolds presented compressive modulus ranging from 17.4 to 62.0 MPa and 4.42 to 27.4 MPa under dry and wet conditions, respectively. Cytotoxicity assays revealed that the hybrid starch/poly-epsilon-caprolactone/Gellan Gum scaffolds were noncytotoxic, as they did not cause major alterations on cell morphology, proliferation, and metabolic viability. Moreover, preliminary cell encapsulation assays showed that the hybrid scaffolds could support the in vitro culture of oligodendrocyte-like cells. Finally, preliminary in vivo studies conducted in a hemisection rat SCI model revealed that the above-referred structures were well integrated within the injury and did not trigger chronic inflammatory processes. The results herein presented indicate that these 3D systems might be of use in future SCI regeneration approaches.
Chronic pain is frequently accompanied by a deterioration of emotional behavior and cognitive function. A small number of studies in humans concluded that pain-associated negative affect is more pronounced when pain is localized in the left side of the body. It has been suggested that such side bias results from cortical function lateralization. It is not known, however, if other pain-associated behavioral changes are differentially affected by left- and right-sided pain. To test this hypothesis, the performance of rats with a unilateral spared nerve injury neuropathy installed in the left (SNI-L) or in the right (SNI-R) side was compared in anxiety (elevated-plus maze) and cognitive (spatial working and reference memory, attentional set-shifting task, and delay-to-signal impulsivity task) behavioral paradigms. Results show that SNI-L animals presented an increased anxiety-like profile while maintaining preserved cognitive function. On the contrary, SNI-R animals presented cognitive deficits in all tasks except in the reference memory, but displayed a normal anxiety-like profile. Our results show that left- and right-sided neuropathic pain differentially affects emotional behavior, which is in accordance with previous observations in human subjects, both in experimentally induced pain and in chronic pain conditions. Additionally, our results demonstrate that the cognitive function deterioration associated with unilateral neuropathic chronic pain conditions is also differentially affected.
The control and manipulation of cells that trigger secondary mechanisms following spinal cord injury (SCI) is one of the first opportunities to minimize its highly detrimental outcomes. Herein, the ability of surface-engineered carboxymethylchitosan/polyamidoamine (CMCht/PAMAM) dendrimer nanoparticles to intracellularly deliver methylprednisolone (MP) to glial cells, allowing a controlled and sustained release of this corticosteroid in the injury site, is investigated. The negatively charged MP-loaded CMCht/PAMAM dendrimer nanoparticles with sizes of 109 nm enable a MP sustained release, which is detected for a period of 14 days by HPLC. In vitro studies in glial primary cultures show that incubation with 200 μg mL(-1) nanoparticles do not affect the cells' viability or proliferation, while allowing the entire population to internalize the nanoparticles. At higher concentrations, microglial cell viability is proven to be affected in response to the MP amount released. Following lateral hemisection lesions in rats, nanoparticle uptake by the spinal tissue is observed 3 h after administration. Moreover, significant differences in the locomotor output between the controls and the MP-loaded nanoparticle-treated animals one month after the lesion are observed. Therefore, MP-loaded CMCht/PAMAM dendrimer nanoparticles may prove to be useful in the reduction of the secondary injury following SCI.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.