Rescue of HSP70 in Spinal Neurons Alleviates Opioids-Induced Hyperalgesia via the Suppression of Endoplasmic Reticulum Stress in Rodents

Lin, Tongtong; Qu, Jie; Wang, Chao-Yu; Yang, Xing; Hu, Fan; Hu, Liang; Wu, Xuefeng; Jiang, Chun-Yi; Li, Wentao; Han, Yuan

doi:10.3389/fcell.2020.00269

Cited by 17 publications

(11 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hua et al [ 57 ] administered mesenchymal stem cells (MSC) either 1 day before, 7 days before, or 14 days after morphine administration. Lin et al [ 58 ] administered heat shock protein 70 (HSP70) using an adenovirus 24 h before, 24 h after, and 72 h after the first morphine injection during a twice a day morphine injection regimen that lasted 6 days. The trial lengths of morphine trials were very variable.…”

Section: Resultsmentioning

confidence: 99%

“…Only four combination interventions were investigated: ketamine and gabapentin, hydrogen-rich saline and Ro 25-6981, PHA-543613 and PNU-120596, and ketamine and KN93. Furthermore, only 17 trials investigated more than one intervention, and only Doyle et al [ 27 ] and Lin et al [ 58 ] investigated more than three interventions. These 17 trials can provide direct comparisons of interventions, although some of the trials slightly varied their experimental methodology between the interventions they tested.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological Interventions for Opioid-Induced Hyperalgesia: A Scoping Review of Preclinical Trials

Koponen

Forget

2022

JCM

View full text Add to dashboard Cite

Background: Opioid analgesics are the most effective pharmacological agents for moderate and severe pain. However, opioid use has several limitations such as opioid-induced hyperalgesia (OIH), which refers to the increased pain sensitivity that occurs once analgesia wears off after opioid administration. Several pharmacological interventions have been suggested for OIH, but the current literature does not provide guidelines on which interventions are the most effective and whether they differ depending on the opioid that induces hyperalgesia. This scoping review aimed to identify and describe all the preclinical trials investigating pharmacological interventions for OIH caused by remifentanil, fentanyl, or morphine as the first step towards evaluating whether the most effective OIH interventions are different for different opioids. Methods: Electronic database searches were carried out in Embase, PubMed, and Web of Science. Detailed data extraction was conducted on the eligible trials. Results: 72 trials were eligible for the review. Of these, 27 trials investigated remifentanil, 14 trials investigated fentanyl, and 31 trials investigated morphine. A total of 82 interventions were identified. The most studied interventions were ketamine (eight trials) and gabapentin (four trials). The majority of the interventions were studied in only one trial. The most common mechanism suggested for the interventions was inhibition of N-methyl-D-aspartate (NMDA) receptors. Conclusion: This scoping review identified plenty of preclinical trials investigating pharmacological interventions for OIH. Using the current literature, it is not possible to directly compare the effectiveness of the interventions. Hence, to identify the most effective interventions for each opioid, the interventions must be indirectly compared in a meta-analysis.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pharmacological Interventions for Opioid-Induced Hyperalgesia: A Scoping Review of Preclinical Trials

Koponen

Forget

2022

JCM

View full text Add to dashboard Cite

show abstract

“…Our RNA sequencing data showed that while this gene was expressed in both sexes, it was specifically upregulated only in males post tumor growth. Interestingly, hsp70 has been demonstrated to have a protective role in pain during nerve damage (99,100), migraine (101) and opioid-induced hyperalgesia (102).Therefore, upregulation of Hsp70 in males post-tumor growth might indicate that male neurons might express an endogenous feedback mechanism to suppress pain that may be lacking in females. In addition to the common BPs, sex-selective BPs were identified post-tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice

Ibrahim

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

While sex-specific prevalence of orofacial pain is established, mechanisms of sex-dependent orofacial pain are widely understudied. To this end, a significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of males and females. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naive as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: 1) Tongue tissue of female mice was innervated with higher number of trigeminal neurons compared to males; 2) Naive female neurons innervating the tongue exclusively expressed immune cell markers such as Csf1R, C1qa and others, that werent expressed in males. This was validated by Immunohistochemistry. 3) Male neurons were more tightly regulated than female neurons upon tumor growth; 4) While very few differentially expressed genes (DEGs) overlapped between males and females post-tumor growth, several biological processes (BPs) were similar between two sexes. However, additional distinct processes were sex-specific; 5) Post-tumor growth, male DEGs contained an equal mix of transcription factors, ligands, growth factors, receptors and channels, whereas female DEGs predominantly contained channels/receptors, enzymes, cytokines and chemokines. Taken together, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, biological pathways and molecular function of tongue-innervating sensory neurons.

show abstract

“…It is well-accepted that chronic morphine administration leads to neuroinflammatory responses in the spinal cord, characterized by the release of proinflammatory cytokines [ 2 ]. In morphine-evoked neuroinflammation, N -methyl- d -aspartate receptor (NMDA-R)-mediated central hyperalgesia plays a vital role in the development of morphine tolerance [ 26 , 27 ]. It was reported that NMDA-R/nitric oxide (NO) pathway antagonists could enhance the antinociceptive effect of morphine.…”

Section: Discussionmentioning

confidence: 99%

AMPK-autophagy-mediated inhibition of microRNA-30a-5p alleviates morphine tolerance via SOCS3-dependent neuroinflammation suppression

Wan

Jia

et al. 2022

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

Background The development of morphine tolerance is a clinical challenge for managing severe pain. Studies have shown that neuroinflammation is a critical aspect for the development of analgesic tolerance. We found that AMPK-autophagy activation could suppress neuroinflammation and improve morphine tolerance via the upregulation of suppressor of cytokine signaling 3 (SOCS3) by inhibiting the processing and maturation of microRNA-30a-5p. Methods CD-1 mice were utilized for the tail-flick test to evaluate morphine tolerance. The microglial cell line BV-2 was utilized to investigate the mechanism of AMPK-autophagy-mediated posttranscriptional regulation of SOCS3. Proinflammatory cytokines were measured by western blotting and real-time PCR. The levels of SOCS3 and miRNA-processing enzymes were evaluated by western blotting, real-time PCR and immunofluorescence staining. Results Based on experimental verification, miRNA-30a-5p could negatively regulate SOCS3. The AMPK activators AICAR, resveratrol and metformin downregulated miRNA-30a-5p. We found that AMPK activators specifically inhibited the processing and maturation of miRNA-30a-5p in microglia by degrading DICER and AGO2 via autophagy. Furthermore, a miRNA-30a-5p inhibitor significantly improved morphine tolerance via upregulation of SCOS3 in mice. It markedly increased the level of SOCS3 in the spinal cord of mice and subsequently inhibited morphine-induced phosphorylation of NF-κB p65. In addition, a miRNA-30a-5p inhibitor decreased the levels of IL-1β and TNF-α caused by morphine in microglia. Conclusion AMPK-autophagy activation suppresses neuroinflammation and improves morphine tolerance via the upregulation of SOCS3 by inhibiting miRNA-30a-5p.

show abstract

Rescue of HSP70 in Spinal Neurons Alleviates Opioids-Induced Hyperalgesia via the Suppression of Endoplasmic Reticulum Stress in Rodents

Cited by 17 publications

References 55 publications

Pharmacological Interventions for Opioid-Induced Hyperalgesia: A Scoping Review of Preclinical Trials

Pharmacological Interventions for Opioid-Induced Hyperalgesia: A Scoping Review of Preclinical Trials

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice

AMPK-autophagy-mediated inhibition of microRNA-30a-5p alleviates morphine tolerance via SOCS3-dependent neuroinflammation suppression

Contact Info

Product

Resources

About