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Application of cytochrome cyp26a1 in preparation of medicine for treating neuropathic pain

A technology of CYP26A1 and cytochrome, which is applied in the field of medicine to achieve the effect of promoting the maintenance of development and alleviating neuropathic pain

Active Publication Date: 2022-04-22
NANTONG UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few reports on the direct involvement of CYP450 superfamily members in regulating the occurrence and development of neuropathic pain.

Method used

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  • Application of cytochrome cyp26a1 in preparation of medicine for treating neuropathic pain
  • Application of cytochrome cyp26a1 in preparation of medicine for treating neuropathic pain
  • Application of cytochrome cyp26a1 in preparation of medicine for treating neuropathic pain

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] CYP26A1 expression is increased during the maintenance phase of SNL-induced neuropathic pain

[0032] 1. Experimental method

[0033] (1) Establishment of mouse spinal nerve ligation (Spinal Nerve Ligation, SNL) neuropathic pain model

[0034]SPF grade 8-week-old male ICR mice were intraperitoneally injected with compound anesthetics, the hair on the back of the waist was shaved with a shaver, and after disinfection with iodine alcohol, a longitudinal incision was made about 5 mm in the left lateral side of the posterior midline, about 1 cm in length, 2 The / 3 incision is made above the iliac crest. Then cut the thoracolumbar fascia, bluntly separate the erector spinae and pull it outward, reveal the transverse process of the 6th lumbar vertebra under the operating microscope and bite off, gently separate the L5 spinal nerve with a glass minute needle, and use a 6-0 gauge Tightly ligate the L5 spinal nerve with silk thread, and then suture the incision layer by layer....

Embodiment 2

[0056] Inhibition of CYP26A1 expression can alleviate SNL-induced mechanical allodynia

[0057] 1. Experimental method:

[0058] (1) Primary astrocyte culture

[0059] Take the neonatal 1-2 day old mouse cerebral cortex in a small petri dish filled with pre-cooled D-Hanks solution, peel off the meninges under a dissecting microscope, collect the cerebral cortex after peeling off the membrane, cut the tissue with scissors, and use a pipette Blow the tissue until there are no fragments, and filter through a 100 μm pore size mesh sieve. Centrifuge at 4°C, 3000g, 5min. Discard the supernatant, add complete medium to resuspend the cells, and filter through a 10 μm pore size filter. Take 2×10 6 (unit / well) The number of cells was inoculated in a 6-well plate, and the medium was changed the next day, and then every 3-4 days. When the confluence of cell growth reached 95%, add d-cAMP (final concentration 150 μM) to induce star formation Glial cells were differentiated and matured...

Embodiment 3

[0077] Inhibition of CYP26A1 function alleviates SNL-induced mechanical allodynia

[0078] 1. Experimental method:

[0079] In the early (3 days) and maintenance (7 days) stages of pain induced by spinal nerve ligation (SNL), intrathecal injection (method is the same as in Example 2) different doses of CYP26A1 inhibitor Talarozole: 0.1ug, 0.5ug , 1ug, behavioral detection of changes in the pain threshold of mice mechanically evoked by touch. Talarazole used in the examples was purchased from MedChem Expree (NJ08852, USA). Talarozole (Talarozole) is an oral all-trans retinoic acid metabolism blocker, which can effectively and selectively inhibit CYP26A1 and CYP26B1, and increase the intracellular level of endogenous all-trans retinoic acid (RA). Treats psoriasis and acne.

[0080] 2. Experimental results: CYP26A1 inhibitor Talarozole can relieve SNL-induced mechanical allodynia

[0081] On the 3rd and 7th day of SNL, intrathecal injection of Talarozole inhibited the functio...

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Abstract

The invention discloses the application of cytochrome enzyme CYP26A1 as a target in preparing a drug for treating neuropathic pain. In the present invention, neuropathic pain is induced by the method of mouse lumbar 5 spinal nerve ligation (SNL), and 10 days after the operation, the mRNA of the lumbar 5 segment of the spinal cord of the mice in the model group and the sham operation group is extracted for gene chip detection, and the neuropathic pain-related genes are screened. , to find potential targets for the development of drugs for the treatment of neuropathic pain. The results showed that the expression of CYP26A1 was increased in the maintenance stage of neuropathic pain, promoting the maintenance and development of neuropathic pain, and inhibiting its expression or function could effectively relieve neuropathic pain. Based on this, with the cytochrome enzyme CYP26A1 as the target, the inhibitor that inhibits its expression and function can be used to screen neuropathic pain treatment drugs, prepare neuropathic pain treatment drugs or prepare neuropathic pain diagnosis drugs.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to the application of cytochrome CYP26A1 as a target in the preparation of drugs for treating neuropathic pain. Background technique [0002] Pain, as a kind of bodily sensation, can act as a warning when the body is injured, triggering a series of defensive protective reactions in the body to avoid further damage. However, when pain loses its normal protective function and persists for several months or years, it becomes pathological pain (chronic pain) that endangers physical and mental health. According to the World Health Organization, chronic pain is the most common condition with the highest disease burden. According to statistics, about 30% of adults suffer from chronic pain. Neuropathic pain (neuropathic pain) is a category of chronic pain, common clinical inflammation, surgery, nerve trauma, viral infection (such as herpes zoster), cancer, metabolic diseases (...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6883A61K45/00A61K31/428A61P25/00A61P29/00
CPCC12Q1/6883A61K45/00A61K31/428A61P25/00A61P29/00C12Q2600/158
Inventor 曹德利高永静姜保春
Owner NANTONG UNIVERSITY