Name	Pain disorders
ICD	ICD-11: 8E43

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	FTO contributes to neuropathic pain through stabilizing nerve injury-induced upregulation of Histone-lysine N-methyltransferase EHMT2 (G9a), a neuropathic pain initiator, in primary sensory neurons.
Responsed Disease	Neuropathic Pain [ICD-11: 8E43.0]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	PC12	Rat adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_0481
In-vivo Model	After the animal was anesthetized with isoflurane, a midline incision in the lower lumbar back region was made and the lumbar articular process was exposed and then removed. The exposed DRG was injected with viral solution (1-1.5 ul in rats and 0.5-1 ul in mice) through a glass micropipette connected to a Hamilton syringe. The pipette was retained for 10 min after injection. Animals showing signs of paresis or other abnormalities were excluded. The injected DRGs were stained with hematoxylin/eosin to examine the integrity of their structure and whether they contained visible leukocytes.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	FTO was colocalized with Matrix metalloproteinase-24 (MMP24) in spinal neurons and shown increased binding to the Mmp24 mRNA in the spinal cord after SNL. SNL promoted the m6A eraser FTO binding to the Mmp24 mRNA, which subsequently facilitated the translation of MMP24 in the spinal cord, and ultimately contributed to neuropathic pain genesis.
Responsed Disease	Neuropathic Pain [ICD-11: 8E43.0]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vivo Model	Mice were anesthetized with Nembutal. The lower back was dissected until the transverse lumbar process was exposed. After the process was removed, the underneath L4 spinal nerve was ligated with a silk 6-0 thread. A slight distal location was chosen for transection around the ligation site. Subsequent layers of muscle and skin were closed. The sham groups undertook identical procedures, but without the transection or ligature of the corresponding nerve. The intraspinal injection was performed as described previously. In short, after anesthetized with Nembutal, mice underwent hemilaminectomy at the L1-L2 vertebral segments. The intraspinal injection was carried out ipsilaterally on the left side. By using a glass micropipette, each animal received two injections (5 × 105 TU per injection, 0.8 mm from the midline, 0.5 mm apart in rostrocaudal axis, 0.5 mm deep) of lentivirus following the L3-L4 dorsal root entry zone after exposure of spinal cord. The tip of glass micropipette should reach a depth of lamina II-IV of the spinal cord. Finally, the dorsal muscle and skin were sutured layer by layer.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Enhanced METTL3 promoted the m6A methylation in total RNAs and inhibited neuropathic pain (NP) progression. Mechanistically, METTL3 accelerated microRNA 150 (MIR150) maturation via mediating m6A methylation of primiR-150 at locus 498, cooperating with the "m6A reader" YTHDF2. Therefore, the METTL3/miR-150/BDNF pathway is a promising therapeutic target for NP patients.
Responsed Disease	Neuropathic Pain [ICD-11: 8E43.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	RN-sc (The rat neuron cell line RN-sc was purchased from ScienCell)
In-vivo Model	Based on our study design, the enrolled animals were blindingly grouped and received the following treatments: (1)Sham-NC vectors, (2)Sham-sh-METTL3, (3)Sham-sh-METTL3 + miR-150, (4)Sham-sh-METTL3 + Lv-YTHDF2, (5)Sham-sh-METTL3 + sh-BDNF, (6)Sham-anti-miR150, (7)Sham-anti-miR150+sh-BDNF, (8)SNI-Lv-METTL3, (9)SNI-Lv-METTL3 + anti-miR-150, (10)SNI-Lv-METTL3 + sh-YTHDF2, (11)SNI-Lv-METTL3 + Lv-BDNF, (12)SNI-miR150, (13)SNI-miR150+Lv-BDNF. The pain behaviors were detected in the respective time points and the expressions of METTL3 and miR-150 were determined at day 14 after the rats were sacrificed.

Ref 1	N(6)-Methyladenosine Demethylase FTO Contributes to Neuropathic Pain by Stabilizing G9a Expression in Primary Sensory Neurons. Adv Sci (Weinh). 2020 May 27;7(13):1902402. doi: 10.1002/advs.201902402. eCollection 2020 Jul.
Ref 2	MMP24 Contributes to Neuropathic Pain in an FTO-Dependent Manner in the Spinal Cord Neurons. Front Pharmacol. 2021 Apr 29;12:673831. doi: 10.3389/fphar.2021.673831. eCollection 2021.
Ref 3	Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51. doi: 10.1074/jbc.M301358200. Epub 2003 Mar 28.
Ref 4	METTL3 suppresses neuropathic pain via modulating N6-methyladenosine-dependent primary miR-150 processing. Cell Death Discov. 2022 Feb 24;8(1):80. doi: 10.1038/s41420-022-00880-2.
Ref 5	A novel asymmetrical anti-HER2/CD3 bispecific antibody exhibits potent cytotoxicity for HER2-positive tumor cells. J Exp Clin Cancer Res. 2019 Aug 14;38(1):355. doi: 10.1186/s13046-019-1354-1.
Ref 6	Clinical pipeline report, company report or official report of vTv Therapeutics.
Ref 7	Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid. Biochem Biophys Res Commun. 2006 Dec 15;351(2):424-30. doi: 10.1016/j.bbrc.2006.10.054. Epub 2006 Oct 17.