scholarly journals Transient decrease in nociceptor GRK2 expression produces long-term enhancement in inflammatory pain

Neuroscience ◽  
2012 ◽  
Vol 222 ◽  
pp. 392-403 ◽  
Author(s):  
L.F. Ferrari ◽  
O. Bogen ◽  
N. Alessandri-Haber ◽  
E. Levine ◽  
R.W. Gear ◽  
...  
Author(s):  
Vojtěch Šimon

Abstract This analysis of the long-term optical activity of the propellers AE Aqr and AR Sco uses data from the Catalina Real-time Transient Survey, DASCH, and AAVSO. The site and character of the emissions from the phenomena caused by the magnetic field of the white dwarf (WD) vary from system to system. The histogram of intensities of the ensemble of flares of AE Aqr suggests that the long-term activity consists of a large variety of the peak magnitudes of the flares, with the probability of their detection gradually decreasing with increasing intensity. Any increase of activity only leads to an increase of the number of blobs of the transferring matter. We also detected a season with a transient decrease or even a cessation of the mass outflow from the donor to the lobe of the WD. The very strong orbital modulation of AR Sco is most stable in the phases of the extrema of brightness for about a century; its minor changes suggest that the trailing side of the synchrotron-emitting region is more unstable than the leading side.


2020 ◽  
Vol 21 (9) ◽  
pp. 3312 ◽  
Author(s):  
Chanya Inprasit ◽  
Yi-Wen Lin

Inflammatory pain sensation is an important symptom which protects the body against additional tissue damage and promotes healing. Discovering long-term and effective treatments for pain remains crucial in providing efficient healthcare. Electroacupuncture (EA) is a successful therapy used for pain relief. We aimed to investigate effects and mechanisms of Complete Freund’s Adjuvant (CFA)-inducing inflammatory pain in the cerebellum, and the inhibition of this inflammatory hyperalgesia using EA at Zusanli acupoint (ST36). The results display a significant increase in mechanical and thermal sensitivities in the CFA and CFA + SHAM groups, which was significantly reduced in the CFA+EA and CFA + KO groups. This evidence was substantiated in the protein levels observed using immunoblotting, and presented with significant escalations after CFA inducing inflammatory hyperalgesia in CFA and CFA + SHAM groups. Then, they were significantly attenuated by EA in the CFA + EA group. Furthermore, the CFA + transient receptor vanilloid member 1 (TRPV1)−/− group indicated similar significant decreases of protein expression. Additionally, a concomitant overexpression in lobule VIa was also observed in immunofluorescence. These consequences suggest that CFA-induced inflammatory pain provokes modifications in cerebellum lobules V, VIa and VII, which can subsequently be regulated by EA treatment at the ST36 through its action on TRPV1 and related molecular pathways.


2017 ◽  
Vol 4 (20;4) ◽  
pp. E575-584 ◽  
Author(s):  
Ya-Qun Zhao

The non-steroidal anti-inflammatory drug celecoxib has long been used for reducing pain, in spite of moderate gastrointestinal side effects. In previous studies, it has been shown that celecoxib can inhibit formalin-induced spontaneous pain and secondary hyperalgesia. Injecting formalin into a rodent’s hind paw not only induces acute pain behaviors, but also produces long-lasting hyperalgesia. Whether celecoxib can also have long-lasting effects is still unknown. Our results show that pretreatment with an intraperitoneal injection of celecoxib at one hour before formalin injection induced inhibition on the spontaneous flinch and licking behaviors in the second phase but not the first phase. Meanwhile, FOS expressions were also reduced with celecoxib pretreatment. Consecutive administration of celecoxib also protects the hind paw from hypoalgesia and relieves formalininduced, long-lasting hyperalgesia in the ipsilateral hind paw. These analgesic effects may be related to suppression of the activation of neurons and astrocytes indicated by FOS and GFAP expressions. Based on the above findings, celecoxib demonstrated analgesic effects not only on acute spontaneous pain behavior but also on long-lasting hyperalgesia induced by formalin injection. The inhibition of neurons and astrocytes by celecoxib may be possible reasons for its analgesia. Key words: Formalin test, celecoxib, FOS, GFAP, hyperalgesia


2021 ◽  
Author(s):  
Manon Bohic ◽  
Luke A. Pattison ◽  
Z. Anissa Jhumka ◽  
Heather Rossi ◽  
Joshua K. Thackray ◽  
...  

Inflammatory pain represents a complex state involving sensitization of peripheral and central neuronal signaling. Resolving this high-dimensional interplay at the cellular and behavioral level is key to effective therapeutic development. Here, using the carrageenan model of local inflammation of the hind paw, we determine how carrageenan alters both the physiological state of sensory neurons and behaviors at rapid and continuous timescales. We identify higher excitability of sensory neurons innervating the site of inflammation by profiling their physiological state at different time points. To identify millisecond-resolved sensory-reflexive signatures evoked by inflammatory pain, we used a combination of supervised and unsupervised algorithms, and uncovered abnormal paw placement as a defining behavioral feature. For long-term detection and characterization of spontaneous behavioral signatures representative of affective-motivational pain states, we use computer vision coupled to unsupervised machine learning in an open arena. Using the non-steroidal anti-inflammatory drug meloxicam to characterize analgesic states during rapid and ongoing timescales, we identify a return to pre-injury states of some sensory-reflexive behaviors, but by and large, many spontaneous, affective-motivational pain behaviors remain unaffected. Taken together, this comprehensive exploration across cellular and behavioral dimensions reveals peripheral versus centrally mediated pain signatures that define the inflamed state, providing a framework for scaling the pain experience at unprecedented resolution.


Pain ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Dominika J. Burek ◽  
Nicolas Massaly ◽  
Michelle Doering ◽  
Azra Zec ◽  
Jordan Gaelen ◽  
...  

1990 ◽  
Vol 10 (2) ◽  
pp. 486-491
Author(s):  
K Kato ◽  
A Kanamori ◽  
H Kondoh

The level of expression of N-myc in mouse teratocarcinoma stem cells is very high. Previous studies have shown that N-myc expression significantly decreases when the stem cells are subjected to long-term induction for differentiation by retinoic acid (RA). We found that in a stem cell line, OTF9, a steep yet transient decrease of N-myc expression takes place much earlier, immediately after induction by RA. To examine whether this decrease is responsible for differentiation, we constructed a gene, miwNmyc, to express N-myc cDNA constitutively and transformed OTF9 cells with this gene construct. Transformants under the constitutive expression of miwNmyc differentiated normally, as judged by morphological changes and by modulation of c-myc, Hox1.1, and laminin B1 expression. Therefore, transient decrease of N-myc expression may be the consequence of RA-induced differentiation, even though it occurs very early in the process. Alternatively, in addition to N-myc decrease, there may be redundant mechanisms which lead to OTF9 differentiation after induction by RA, so that suppression of N-myc decrease is bypassed by at least one other mechanism.


2020 ◽  
Vol 8 (12) ◽  
Author(s):  
Soo Seo ◽  
Ronny Priefer

Since the very first medical use of dexamethasone (DEX) in 1958, this glucocorticoid (GC) has been widely used in various clinical applications. Compared to other GCs, DEX is highly potent and comes in multiple formulations for ease of local and systemic administrations. Recently, DEX has a new application for treating COVID-19 patients. DEX mainly inhibits expressions of inflammatory proteins and transcription factors necessarily for cell proliferation. DEX can both upregulate and downregulate expressions of the genes that facilitates anti- inflammatory effects and immunosuppression. Key proteins involved in DEX pathways are NF- B, AP-1, COX-2, and annexin A1. When used appropriately, DEX can minimize inflammatory pain and damage but it can also delay patient recovery by immunosuppression. Due to this duality, DEX should be used with caution for treatment considerations. Long-term systemic use could lead to debilitating adverse reactions and firm recommendations should be established in treating both acute and chronic disease with DEX.


1990 ◽  
Vol 10 (2) ◽  
pp. 486-491 ◽  
Author(s):  
K Kato ◽  
A Kanamori ◽  
H Kondoh

The level of expression of N-myc in mouse teratocarcinoma stem cells is very high. Previous studies have shown that N-myc expression significantly decreases when the stem cells are subjected to long-term induction for differentiation by retinoic acid (RA). We found that in a stem cell line, OTF9, a steep yet transient decrease of N-myc expression takes place much earlier, immediately after induction by RA. To examine whether this decrease is responsible for differentiation, we constructed a gene, miwNmyc, to express N-myc cDNA constitutively and transformed OTF9 cells with this gene construct. Transformants under the constitutive expression of miwNmyc differentiated normally, as judged by morphological changes and by modulation of c-myc, Hox1.1, and laminin B1 expression. Therefore, transient decrease of N-myc expression may be the consequence of RA-induced differentiation, even though it occurs very early in the process. Alternatively, in addition to N-myc decrease, there may be redundant mechanisms which lead to OTF9 differentiation after induction by RA, so that suppression of N-myc decrease is bypassed by at least one other mechanism.


2013 ◽  
Vol 305 (8) ◽  
pp. H1111-H1119 ◽  
Author(s):  
Wenjuan Xing ◽  
Youyou Li ◽  
Haifeng Zhang ◽  
Chunjuan Mi ◽  
Zuoxu Hou ◽  
...  

Exercise training lowers blood pressure and is a recommended nonpharmacological strategy and useful adjunctive therapy for hypertensive patients. Studies demonstrate that physical activity attenuates progression of hypertension. However, underlying mechanisms remain elusive. Vascular insulin resistance and endothelial dysfunction plays a critical role in the development of hypertension. The present study investigated whether long-term physical exercise starting during the prehypertensive period prevents the development of hypertension via improving vascular insulin sensitivity. Young (4 wk old) prehypertensive spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) control rats were subjected to a 10-wk free-of-loading swim training session (60 min/day, 5 days/wk). Blood pressure, mesenteric arteriolar vasorelaxation, G protein-coupled receptor kinase-2 (GRK2) expression and activity, and insulin-stimulated Akt/endothelial nitric oxide synthase (eNOS) activation were determined. SHRs had higher systolic blood pressure, systemic insulin resistance, and impaired vasodilator actions of insulin in resistance vessels when compared with WKY rats. Systolic blood pressure in SHRs postexercise was significantly lower than that in sedentary rats. Vascular insulin sensitivity in mesenteric arteries was improved after exercise training as evidenced by an increased vasodilator response to insulin. In addition, exercise downregulated vascular GRK2 expression and activity, which further increased insulin-stimulated vascular Akt/eNOS activation in exercised SHRs. Specific small interfering RNA knockdown of GRK2 in endothelium mimicked the effect of exercise-enhanced vascular insulin sensitivity. Likewise, upregulation of GRK2 by Chariot-mediated delivery opposed exercise-induced vascular insulin sensitization. Taken together, our results suggest that long-term exercise beginning at the prehypertensive stage improves vascular insulin sensitivity via downregulation of vascular GRK2 that may help to limit the progression of hypertension.


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