Disease Information

General Information of the Disease (ID: DIS00008)

• Name: Pain
• ICD: ICD-11: MG30

Type(s) of Resistant Mechanism of This Disease

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Dezocine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-124-3p [1]

• Resistant Disease: Pain [ICD-11: MG30.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Dezocine
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: Western blot analysis; Quantitative reverse-transcription PCR assay
• Mechanism Description: miR-124-3p alleviates the dezocine tolerance against pain by regulating TRAF6 in a rat model. miR-124-3p expression was highly downregulated in a dezocine-resistant model. miR-124-3p overexpression could alleviate dezocine tolerance in rats. TRAF6 expression was significantly upregulated in a dezocine-resistant model. miR-124-3p targeted TRAF6 and TRAF6 was negatively modulated by miR-124-3p. In addition, overexpression of TRAF6 could reverse the inhibitory effects of miR-124-3p on dezocine tolerance. Overexpression of miR-124-3p alleviates dezocine tolerance against pain via regulating TRAF6 in a rat model, providing a possible solution to address dezocine tolerance in clinical.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: TNF receptor-associated factor 6 (TRAF6) [1]

• Resistant Disease: Pain [ICD-11: MG30.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Dezocine
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: Western blot analysis; Quantitative reverse-transcription PCR assay
• Mechanism Description: miR-124-3p alleviates the dezocine tolerance against pain by regulating TRAF6 in a rat model. miR-124-3p expression was highly downregulated in a dezocine-resistant model. miR-124-3p overexpression could alleviate dezocine tolerance in rats. TRAF6 expression was significantly upregulated in a dezocine-resistant model. miR-124-3p targeted TRAF6 and TRAF6 was negatively modulated by miR-124-3p. In addition, overexpression of TRAF6 could reverse the inhibitory effects of miR-124-3p on dezocine tolerance. Overexpression of miR-124-3p alleviates dezocine tolerance against pain via regulating TRAF6 in a rat model, providing a possible solution to address dezocine tolerance in clinical.

Loperamide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [2]

• Sensitive Disease: Pain [ICD-11: MG30.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Loperamide
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: ATPase activity assay
• Mechanism Description: P-glycoprotein (Pgp) is a multidrug resistance transporter that limits the penetration of a wide range of neurotherapeutics into the brain including opioids. Pgp-knockout mice had more than a 10-fold higher level of loperamide in their brains than wild-type. Both rats and humans have shown elevated levels of loperamide in the presence of the Pgp-specific inhibitor cyclosporine A.

Methadone

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [2]

• Sensitive Disease: Pain [ICD-11: MG30.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Methadone
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: ATPase activity assay
• Mechanism Description: P-glycoprotein (Pgp) is a multidrug resistance transporter that limits the penetration of a wide range of neurotherapeutics into the brain including opioids. Pgp-knockout mice had more than a 10-fold higher level of loperamide in their brains than wild-type. Both rats and humans have shown elevated levels of loperamide in the presence of the Pgp-specific inhibitor cyclosporine A.

References

• Ref 1: MiR-124-3p alleviates the dezocine tolerance against pain by regulating TRAF6 in a rat model .Neuroreport. 2021 Jan 6;32(1):44-51. doi: 10.1097/WNR.0000000000001559. 10.1097/WNR.0000000000001559
• Ref 2: A Conformationally Gated Model of Methadone and Loperamide Transport by P-Glycoprotein. J Pharm Sci. 2018 Jul;107(7):1937-1947. doi: 10.1016/j.xphs.2018.02.019. Epub 2018 Feb 28.