scholarly journals Insulin Within the Arcuate Nucleus Has Paradoxical Effects on Nociception in Healthy and Diabetic Rats

2020 ◽  
Vol 11 (6) ◽  
pp. 727-736
Author(s):  
Hossein Khaleghzadeh-Ahangar ◽  
◽  
Forouzan Sadeghimahalli ◽  
Shaghayegh Khandan ◽  
Sima Shahabi ◽  
...  

Introduction: Broad neural circuits originate from the hypothalamic arcuate nucleus and project to many parts of the brain which are related to pain perception. Insulin receptors are found in the arcuate nucleus. Since nociception may be affected in type 1 diabetes, the present study aimed to investigate the intra-arcuate nucleus insulin role in pain perception in streptozotocin (STZ)-induced diabetic and healthy rats. Methods: Regular insulin was microinjected within the arcuate nucleus and the pain tolerance was measured using the hot plate and the tail-flick apparatus in diabetic rats. Results: The results showed that the arcuate nucleus suppression with lidocaine could increase thermal nociception in non-diabetic animals. Also, insulin within the arcuate nucleus decreased the acute thermal pain perception in these animals. STZ-induced diabetes produced hypoalgesia which the latency of these tests, progressively increased over time after induction of diabetes. Also, in the same animal group, intra-arcuate injection of insulin reduced the latency of nociception. Conclusion: Intra-arcuate insulin has paradoxical and controversial effects in healthy and diabetic rats’ nociception. These effects seem to be due to the insulin effect on releasing pro-opiomelanocortin and its deriv

Crisis ◽  
2019 ◽  
Vol 40 (6) ◽  
pp. 413-421 ◽  
Author(s):  
Megan L. Rogers ◽  
Thomas E. Joiner

Abstract. Background: Acute suicidal affective disturbance (ASAD) has been proposed as a suicide-specific entity that confers risk for imminent suicidal behavior. Preliminary evidence suggests that ASAD is associated with suicidal behavior beyond a number of factors; however, no study to date has examined potential moderating variables.  Aims: The present study tested the hypotheses that physical pain persistence would moderate the relationship between ASAD and (1) lifetime suicide attempts and (2) attempt lethality. Method: Students ( N = 167) with a history of suicidality completed self-report measures assessing the lifetime worst-point ASAD episode and the presence of a lifetime suicide attempt, a clinical interview about attempt lethality, and a physical pain tolerance task. Results: Physical pain persistence was a significant moderator of the association between ASAD and lifetime suicide attempts ( B = 0.00001, SE = 0.000004, p = .032), such that the relationship between ASAD and suicide attempts strengthened at increasing levels of pain persistence. The interaction between ASAD and pain persistence in relation to attempt lethality was nonsignificant ( B = 0.000004, SE = 0.00001, p = .765). Limitations: This study included a cross-sectional/retrospective analysis of worst-point ASAD symptoms, current physical pain perception, and lifetime suicide attempts. Conclusion: ASAD may confer risk for suicidal behavior most strongly at higher levels of pain persistence, whereas ASAD and pain perception do not influence attempt lethality.


2020 ◽  
Vol 8 (3) ◽  
pp. 239-254 ◽  
Author(s):  
Reza Mahjub ◽  
Farzane K. Najafabadi ◽  
Narges Dehkhodaei ◽  
Nejat Kheiripour ◽  
Amir N. Ahmadabadi ◽  
...  

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ioana-Mirela Vasincu ◽  
Maria Apotrosoaei ◽  
Sandra Constantin ◽  
Maria Butnaru ◽  
Liliana Vereștiuc ◽  
...  

Abstract Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cytotoxicity and toxicity degree on mice, revealed that the ibuprofen derivatives (4a-n) are non-cytotoxic at 2 μg/ml. In addition, ibuprofen derivatives reduced carrageenan-induced paw edema in rats, for most of them the maximum effect was recorded at 4 h after administration which means they have medium action latency, similar to that of ibuprofen. Moreover, for compound 4d the effect was higher than that of ibuprofen, even after 24 h of administration. The analgesic effect evaluation highlighted that 4 h showed increased pain inhibition in reference to ibuprofen in thermal (tail-flick assay) and visceral (writhing assay) nociception models. Conclusions The study revealed for ibuprofen derivatives, noted as 4 m, 4 k, 4e, 4d, a good anti-inflammatory and analgesic effect and also a safer profile compared with ibuprofen. These findings could suggest the promising potential use of them in the treatment of inflammatory pain conditions.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Krzysztof Basiński ◽  
Agata Zdun-Ryżewska ◽  
David M. Greenberg ◽  
Mikołaj Majkowicz

AbstractMusic-induced analgesia (MIA) is a phenomenon that describes a situation in which listening to music influences pain perception. The heterogeneity of music used in MIA studies leads to a problem of a specific effect for an unspecified stimulus. To address this, we use a previously established model of musical preferences that categorizes the multidimensional sonic space of music into three basic dimensions: arousal, valence and depth. Participants entered an experimental pain stimulation while listening to compilations of short musical excerpts characteristic of each of the three attribute dimensions. The results showed an effect on the part of music attribute preferences on average pain, maximal pain, and pain tolerance after controlling for musical attributes and order effects. This suggests that individual preferences for music attributes play a significant role in MIA and that, in clinical contexts, music should not be chosen arbitrarily but according to individual preferences.


2021 ◽  
pp. 003329412098809
Author(s):  
Paul K. Miller ◽  
Sophie Van Der Zee ◽  
David Elliott

In recent years a considerable body of psychological research has explored the relationship between membership of socio-cultural groups and personal pain perception. Rather less systematic attention has, however, been accorded to how such group membership(s) might influence individual attitudes towards the pain of others. In this paper, immersion in the culture of competitive sport, widely regarded as being exaggeratedly tolerant of risky behaviours around pain, is taken as a case-in-point with students of Physical Education (PE) in tertiary education as the key focus. PE students are highly-immersed in competitive sporting culture both academically and (typically) practically, and also represent a key nexus of cross-generational transmission regarding the norms of sport itself. Their attitudes towards the pain that others should reasonably tolerate during a range of activities, sporting and otherwise, were evaluated through a direct comparison with those of peers much less immersed in competitive sporting culture. In total, N=301 (144 PE, 157 non-PE) undergraduate students in the UK responded to a vignette-based survey. Therein, all participants were required to rate the pain (on a standard 0-10 scale) at which a standardised “other” should desist engagement with a set of five defined sporting and non-sporting tasks, each with weak and strong task severities. Results indicated that PE students were significantly more likely to expect others to persevere through higher levels of pain than their non-PE peers, but only during the sport-related tasks – an effect further magnified when task severity was high. In other tasks, there was no significant difference between groups, or valence of the effect was actually reversed. It is argued that the findings underscore some extant knowledge about the relationship between acculturated attitudes to pain, while also having practical implications for understanding sport-based pedagogy, and its potentially problematic role in the ongoing reproduction of a “culture of risk.”


2011 ◽  
Vol 02 (02) ◽  
pp. 130-136 ◽  
Author(s):  
Keshab Raj Paudel ◽  
SK Bhattacharya ◽  
GP Rauniar ◽  
BP Das

ABSTRACT Introduction: Newer anticonvulsants have a neuromodulatory effect on pain perception mechanisms in a hyperexcitable and damaged nervous system. Aim: This study was designed to study the analgesic effects of gabapentin alone and in combination with lamotrigine and topiramate in experimental pain models. Materials and Methods: Adult albino mice (n = 490) weighing 20–30 g and rats (n = 130) weighing 100–200 g were injected intraperitoneally with gabapentin, lamotrigine, and topiramate alone and in different dose combinations. The hot-plate method, tail-flick method, capsaicin-induced mechanical hyperalgesia, and formalin assay were used to assess the antinociceptive effects. Results: Of the three antiepileptic drugs, when given separately, gabapentin was more efficacious than either topiramate or lamotrigine in all the pain models. Combination of 25 mg/kg gabapentin with 25 mg/kg topiramate was more efficacious (P <.05) than 50 mg/kg gabapentin alone in the capsaicin-induced mechanical hyperalgesia test. Similarly, 50 mg/kg gabapentin with 50 mg/kg topiramate or 5 mg/kg lamotrigine was more efficacious (P <.05) than 50 or 100 mg/kg gabapentin alone in late-phase formalin-induced behaviors. Conclusions: Combination of gabapentin with either lamotrigine or topiramate produced better results than gabapentin alone in capsaicin-induced mechanical hyperalgesia test and in late-phase formalin-induced behaviors.


2019 ◽  
Author(s):  
Richard Stephens ◽  
Olly May Robertson

Background: This pre-registered study extends previous findings that swearing alleviates pain tolerance by assessing the effects of a conventional swear word (“fuck”) and two new “swear” words, “fouch” and “twizpipe”.Method: A mixed sex group of participants (N = 92) completed a repeated measures experimental design augmented by mediation analysis. The independent variable was Word with the levels, “fuck” v. “fouch” v. “twizpipe” v. a neutral word. The dependent variables were emotion rating, humour rating, distraction rating, cold pressor pain threshold, cold pressor pain tolerance, pain perception score and change from resting heart rate. Possible mediation effects were assessed for emotion, humour and distraction ratings. Results: For conventional swearing (“fuck”), confirmatory analyses found a 32% increase in pain threshold and a 33% increase in pain tolerance, accompanied by increased ratings for emotion, humour and distraction, relative to the neutral word condition. The new “swear” words, “fouch” and “twizpipe” were rated higher than the neutral word for emotion and humour although these words did not affect pain threshold or tolerance. Changes in heart rate, pain perception and were absent, as were mediation effects.Conclusions: Our data replicate previous findings that repeating a swear word at a steady pace and volume benefits pain tolerance, extending this finding to pain threshold. Our data cannot explain how such effects are manifest, although distraction appears to be of little importance, and emotion is worthy of future study. The new “swear” words did not alleviate pain even though participants rated them as emotion evoking and humorous.


Author(s):  
Siamak Shahidi ◽  
◽  
Alireza Komaki ◽  
Safoura Raoufi ◽  
Iraj Salehi ◽  
...  

Background/Aim: Hyperalgesia is one of the current complications of diabetes mellitus that Oxidative stress and inflammation have principal role in its development. Ellagic Acid (EA) as a herbal component, has some biological activities, including antioxidant and anti-inflammatory effects. This study was designed to evaluate the possible beneficial effect of EA on hyperalgesia in streptozotocin (STZ)-induced diabetic rat. Materials and Methods: Rats were divided into control(vehicle received), diabetic, EA (25, 50 mg/kg)-treated control and EA(25, 50 mg/kg)-treated diabetic groups. Diabetes was induced by a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg/Kg). EA was administered daily by oral gavage for 4 weeks. Hyperalgesia was assessed using tail flick (TF) and hot plate (HP) tests. Also, oxidative stress markers including malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant capacity (TAC) in the serum were evaluated. Results: Diabetic animals showed marked reductions in TF and HP latencies, elevation of serum MDA level and TOS and diminution of serum TAC compared to controls significantly. Treatment of Diabetic rats with EA ameliorated reduction of TF latency at the dose of 25 mg/kg and HP latency at the dose of 50 mg/kg. Furthermore EA significantly increased TAC and decreased MDA level at dose of 50 mg/kg and reduced TOS at both doses in the serum of diabetic animals. In EA treated normal rats we could see no significant alterations in the parameters studied. Conclusion: These results displayed potent antinociceptive effect of EA in diabetic rats via attenuating oxidative stress. This proposes therapeutic potential of EA for damping diabetic hyperalgesia.


2019 ◽  
Vol 10 (4) ◽  
pp. 313-322
Author(s):  
Farshid Etaee ◽  
◽  
Arezoo Rezvani-Kamran ◽  
Mohammad Taheri ◽  
Ghazaleh Omidi ◽  
...  

Introduction: Methamphetamine (Meth) and Buprenorphine (BUP) modulate pain perception. However, the antinociceptive effects of their interactions, which affect through different systems, are unclear in rats. This study aimed to compare the analgesic effects of Meth, BUP, and their coadministration, as well as the effect of withdrawal from these substances on nociception in male rats. Methods: In this experiment, 40 male Wistar rats (weight: 250-300 g) were categorized into four groups: control, Meth, BUP, or BUP+Meth. After seven days of treatments, the antinociceptive effects were assessed using the hot plate and the tail flick tests. The differences among the groups were analyzed with ANOVA and Tukey’s post hoc tests. P values less than 0.05 were considered significant. Results: Meth and BUP increased the reaction times during the hot plate and tail flick tests. The combination of Meth and BUP increased reaction time more than Meth or BUP alone.  Conclusion: The significantly high reaction times in rats treated with Meth and BUP indicate that these substances have antinociceptive effects. In addition, Meth enhanced the antinociceptive effects of BUP. These synergistic effects might occur through the dopaminergic, serotonergic, and or adrenergic systems.


Author(s):  
KAMNI RAJPUT ◽  
RAMESH CHANDRA DUBEY

Objective: In vitro antioxidant activity, in vivo antidiabetic property and intestinal attachment by two potential probiotic bacterial strains, namely, Enterococcus faecium and Enterococcus hirae were studied using albino rats. Methods: Antioxidant the activity was assessed using 2,2-Diphenyl-1-picrylhydrazyl radicals scavenging assay. Alloxan was administered intraperitoneally to induce diabetic conditions in experimental rats. Animals were treated with oral administration of Enterococcus spp., such as E. faecium, and E. hirae isolated from goat and sheep milk. The control animal group received normal saline for the same days. Glibenclamide drug was used as a positive control against probiotic bacterial cells. Results: However, administration of probiotic bacterial strains E. faecium and E. hirae, in albino rats significantly (p<0.05) at varying doses lowered blood glucose levels in diabetic rats as compared to the diabetic control group. Both the species of Enterococcus increased the bodyweight of experimental rats. However, E. faecium was the best antidiabetic strain having the antioxidant activities also in comparison to E. hirae. The attachment of probiotic bacterial cells E. faecium on the rat’s intestine wall against pathogens was examined. Furthermore, E. faecium showed its aggregation with pathogens by attachment of the intestines of albino rats. This showed that both the bacterial strains exhibited in vivo antidiabetic effect. Conclusion: The results of this study showed that probiotic bacteria possess antioxidant, antidiabetic activities, and attachment of intestine.


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