Background
Diffuse noxious inhibitory controls (DNIC) as measured in rat and conditioned pain modulation (CPM), the supposed psychophysical paradigm of DNIC measured in humans, are unique ...manifestations of an endogenous descending modulatory pathway that is activated by the application of a noxious conditioning stimulus. The predictive value of the human CPM processing is crucial when deliberating the translational worth of the two phenomena.
Methods
For CPM or DNIC measurement, test and conditioning stimuli were delivered using a computer‐controlled cuff algometry system or manual inflation of neonate blood pressure cuffs, respectively. In humans (n = 20), cuff pain intensity (for pain detection and pain tolerance thresholds) was measured using an electronic visual analogue scale. In isoflurane‐anaesthetized naïve rats, nociception was measured by recording deep dorsal horn wide dynamic range (WDR) neuronal firing rates (n = 7) using in vivo electrophysiology.
Results
A painful cuff‐pressure conditioning stimulus on the leg increased pain detection and pain tolerance thresholds recorded by cuff stimulation on the contralateral leg in humans by 32% ± 3% and 24% ± 2% (mean ± SEM) of baseline responses, respectively (p < .001). This finding was back‐translated by revealing that a comparable cuff‐pressure conditioning stimulus (40 kPa) on the hind paw inhibited the responses of WDR neurons to noxious contralateral cuff test stimulation to 42% ± 9% of the baseline neuronal response (p = .003).
Conclusions
These data substantiate that the noxious cuff pressure paradigm activates the descending pain modulatory system in rodent (DNIC) and man (CPM), respectively. Future back and forward translational studies using cuff pressure algometry may reveal novel mechanisms in varied chronic pain states.
Significance
This study provides novel evidence that a comparable noxious cuff pressure paradigm activates a unique form of endogenous inhibitory control in healthy rat and man. This has important implications for the forward translation of bench and experimental pain research findings to the clinical domain. If translatable mechanisms underlying dysfunctional endogenous inhibitory descending pathway expression (previously evidenced in painful states in rat and man) were revealed using cuff pressure algometry, the identification of new analgesic targets could be expedited.
Bulbospinal pathways regulate nociceptive processing, and inhibitory modulation of nociception can be achieved via the activity of diffuse noxious inhibitory controls (DNIC), a unique descending ...pathway activated upon application of a conditioning stimulus (CS). Numerous studies have investigated the effects of varied pharmacological systems on the expression status of a) DNIC (as measured in anaesthetised animals) and b) the descending control of nociception (DCN), a surrogate measure of DNIC-like effects in conscious animals. However, the complexity of the underlying circuitry that governs initiation of a top-down inhibitory response in reaction to a CS, coupled with the methodological limitations associated with using pharmacological tools for its study, has often obscured the exact role(s) of a given drug. In this literature review, we discuss the pharmacological manipulation interrogation strategies that have hitherto been used to examine the functionality of DNIC and DCN. Discreet administration of a substance in the spinal cord or brain is considered in the context of action on one of four hypothetical systems that underlie the functionality of DNIC/DCN, where interpreting the outcome is often complicated by overlapping qualities. Systemic pharmacological modulation of DNIC/DCN is also discussed despite the fact that the precise location of drug action(s) cannot be pinpointed. Chiefly, modulation of the noradrenergic, serotonergic and opioidergic transmission systems impacts DNIC/DCN in a manner that relates to drug class, route of administration and health/disease state implicated. The advent of increasingly sophisticated interrogation tools will expedite our full understanding of the circuitries that modulate naturally occurring pain-inhibiting pathways.
The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch, and skin temperature. Despite its ...importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here, we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters of ALS neurons (ALS1-5) and document their laminar distribution in the spinal cord using in situ hybridization. We identify three clusters of neurons located predominantly in laminae I-III of the dorsal horn (ALS1-3) and two clusters with cell bodies located in deeper laminae (ALS4 and ALS5). Our findings reveal the transcriptional logic that underlies ALS neuronal diversity in the adult mouse and uncover the molecular identity of two previously identified classes of projection neurons. We also show that these molecular signatures can be used to target groups of ALS neurons using retrograde viral tracing. Overall, our findings provide a valuable resource for studying somatosensory biology and targeting subclasses of ALS neurons.
Embryonic development of lower vertebrates can be influenced by many factors, especially when outside of the mother's body and under the influence of variable abiotic and biotic factors. In this ...study, the effects of fertilization of post-ovulatory aged (overmature) oocytes of ide Leuciscus idus on the risk of developing anomalies in ide larvae were assessed under controlled conditions. There was a negative effect of delayed fertilization of post-ovulatory aged (overmature) oocytes in the ovary on the quality of offspring, which caused reduced survival 3 days post-fertilization and at the hatching stage (68.3 vs. 81.2% and 47.2 vs. 79.7% for the overmature and mature groups, respectively). It also increased the occurrence of numerous developmental defects (19.3 vs. 0.8% for the overmature and mature groups, respectively), including the development of Siamese twins. This is the first reported case of the occurrence of Siamese twins in ide. The ide Siamese twins look like hen eggs with 2 heads and are different from 'typical' Siamese twins in fish.
The burbot (Lota L.) is one of the most promising freshwater new fish species for cold-water aquaculture. Due to the lack of availability of wild spawners, it is imperative to breed cultured ...spawners. In the present study, artificial reproduction of a cultured stock of burbot was carried out and then compared with wild fish reproduction results. Patterns of burbot final oocyte maturation were developed and they were compared during artificial reproduction of wild and cultured burbot. For the first time, a model of final oocyte maturation (FOM) was formulated in a hormonally stimulated female burbot. The relationship between the oocyte maturity stage is straightforward and, at a water temperature of 2 °C, progress by the next stage was observed in two-day intervals. This model was tested on a group of wild and cultured fish (generation F1) originating from the Vistula Lagoon (Northern Poland). In both cases, the very high utility of the proposed model in the artificial reproduction of burbot was confirmed. The fertilization was very high. In wild and cultured forms was similar and was over 95% (95.4 ± 0.3 and 95.3 ± 0.3 as mean ± SD for wild and cultured, respectively). The differences in the survival to eyed-egg-stage (92.2 ± 0.8 and 91.9 ± 0.7 for wild and cultured, respectively) and hatchability of eggs (91.1 ± 0.9 and 90.9 ± 0.8 for wild and cultured, respectively) were statistically insignificant. In summary, a cultured stock of burbot spawners can be successfully used for the stable production of the stocking material of this species.
•A cultured stock can stabilize the production of burbot fry under hatchery conditions.•Burbot can be spawned in a selected period using appropriate stimulation with environmental conditions.•The method of oocyte maturity assessment used in Eurasian perch and pikeperch can be successfully used in burbot.
Abstract
In 2018, a test run with muons in the North Area at CERN was
performed, running parasitically downstream of the COMPASS
spectrometer. The aim of the test was to investigate the elastic
...interactions of muons on atomic electrons, in an experimental
configuration similar to the one proposed by the project MUonE,
which plans to perform a very precise measurement of the
differential cross-section of the elastic interactions.
COMPASS was taking data with a 190 GeV π beam, stopped in a
tungsten beam dump: the muons from these π decays passed through
a setup including a graphite target followed by 10 planes of Si
tracker and a BGO crystal electromagnetic calorimeter placed at the
end of the tracker. The elastic scattering events were selected and
analysed, and compared to expectations from MonteCarlo
simulation. The agreement found was satisfactory and demonstrated
that measuring the angles of the outgoing particles, a clean sample
of elastic interaction could be identified.
Hopes for the Future of Pain Control Bannister, Kirsty; Kucharczyk, Mateusz; Dickenson, Anthony H.
Pain and therapy,
12/2017, Letnik:
6, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Here we aim to present an accessible review of the pharmacological targets for pain management, and succinctly discuss the newest trends in pain therapy. A key task for current pain pharmacotherapy ...is the identification of receptors and channels orchestrating nociception. Notwithstanding peripheral alterations in the receptors and channels following pathophysiological events, the modulatory mechanisms in the central nervous system are also fundamental to the regulation of pain perception. Bridging preclinical and clinical studies of peripheral and central components of pain modulation, we present the different types of pain and relate these to pharmacological interventions. We firstly highlight the roles of several peripheral nociceptors, such as NGF, CGRP, sodium channels, and TRP-family channels that may become novel targets for therapies. In the central nervous system, the roles of calcium channels and gabapentinoids as well as NMDA receptors in generating excitability are covered including ideas on central sensitization. We then turn to central modulatory systems and discuss opioids and monoamines. We aim to explain the importance of central sensitization and the dialogue of the spinal circuits with the brain descending modulatory controls before discussing a mechanism-based effectiveness of antidepressants in pain therapy and their potential to modulate the descending controls. Emphasizing the roles of conditioned pain modulation and its animal’s equivalent, diffuse noxious inhibitory controls, we discuss these unique descending modulations as a potential tool for understanding mechanisms in patients suffering from pain. Mechanism-based therapy is the key to picking the correct treatments and recent clinical studies using sensory symptoms of patients as surrogates for underlying mechanisms can be used to subgroup patients and reveal actions of drugs that may be lost when studying heterogenous groups of patients. Key advances in the understanding of basic pain principles will impact our thinking about therapy targets. The complexity of pain syndromes will require tailored pharmacological drugs, often in combination or through drugs with more than one action, and often psychotherapy, to fully control pain.
This study aimed to determine the dietary effects of honeybee pollen (BP) on growth parameters, intestinal microbiota, hepatic histoarchitecture, and intestinal histomorphometry of African catfish ...Clarias gariepinus juveniles. The feeding experiment was carried out in a recirculating aquaculture system under controlled conditions for 21 days to achieve more than a 10-fold increase in weight in fish from the control group. Fish were fed well-balanced commercial feed without any supplements and served as a reference group (group C) and other diets enriched with varying BP levels as 1% (BP1), 2% (BP2), and 3% (BP3). Results showed a significant (p < 0.05) effect of the dietary BP not only on the growth parameters (such as final body weight: 5.0 g to 6.6−7.5 g, weight gain: 0.23 g/d to 0.31−0.35 g/d, body length: 84.7 mm to 93.8−95.9 mm, and specific growth rate: 11.7%/d to 13.1−13.7%/d, group C vs. experimental groups, respectively) but also on the development of beneficially important gut microbiota, such as lactic acid-producing bacteria. In BP-enriched groups, an average of 45% higher body weight gain was observed compared to those reared in the control group. The histological analysis showed that dietary BP may have a positive effect on the development of the intestinal tract and may enhance the absorption of nutrients with the potential ability to maintain a normal hepatic histoarchitecture of the treated African catfish. The results obtained suggest the optimum level of BP additive to feed for African catfish should be 1%.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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