22 research outputs found
Practical synthesis of 5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin-5-ol (cotarnine)
Upregulation of ERK phosphorylation in rat dorsal root ganglion neurons contributes to oxaliplatin-induced chronic neuropathic pain.
Oxaliplatin is the first-line chemotherapy for metastatic colorectal cancer. Unlike other platinum anticancer agents, oxaliplatin does not result in significant renal impairment and ototoxicity. Oxaliplatin, however, has been associated with acute and chronic peripheral neuropathies. Despite the awareness of these side-effects, the underlying mechanisms are yet to be clearly established. Therefore, in this study, we aimed to understand the factors involved in the generation of chronic neuropathy elicited by oxaliplatin treatment. We established a rat model of oxaliplatin-induced neuropathic pain (4 mg kg-1 intraperitoneally). The paw withdrawal thresholds were assessed at different time-points after the treatment, and a significant decrease was observed 3 and 4 weeks after oxaliplatin treatment as compared to the vehicle treatment (4.4 ± 1.0 vs. 16.0 ± 4.1 g; P < 0.05 and 4.4 ± 0.7 vs. 14.8 ± 3.1 g; P < 0.05, respectively). We further evaluated the role of different mitogen-activated protein kinases (MAPKs) pathways in the pathophysiology of neuropathic pain. Although the levels of total extracellular signal-regulated kinase (ERK) 1/2 in the dorsal root ganglia (DRG) were not different between oxaliplatin and vehicle treatment groups, phosphorylated ERK (p-ERK) 1/2 was up-regulated up to 4.5-fold in the oxaliplatin group. Administration of ERK inhibitor PD98059 (6 μg day-1 intrathecally) inhibited oxaliplatin-induced ERK phosphorylation and neuropathic pain. Therefore, upregulation of p-ERK by oxaliplatin in rat DRG and inhibition of mechanical allodynia by an ERK inhibitor in the present study may provide a better understanding of intracellular molecular alterations associated with oxaliplatin-induced neuropathic pain and help in the development of potential therapeutics
Neuromedin U Depolarizes Rat Hypothalamic Paraventricular Nucleus Neurons In Vitro by Enhancing I
Nociceptin modulates renal sympathetic nerve activity through a central action in conscious rats
Distribution of ChR2-EYFP channels in DRG.
The green fluorescent signal represents the direct fluorescence of ChR2-EYFP. (a) 20× and (b) 40×. (PPTX)</p
Fig 1 -
Schematic diagram of the Scn9aiCre knock-in allele (a) and PCR for genotyping founder mice (b). (a)The last exon of Scn9a is illustrated. The P2A-iCre sequence was inserted immediately after the stop codon of Scn9a. (b) The detection of the insert upstream of the 5′- and 3′-homology arm and the random integration of pX330-mC and piCre-Scn9a. Six founder mice were determined to carry the designed knock-in mutation. M, marker; P, positive control; N, negative control.</p