Intranasal delivery of siRNA targeting NR2B attenuates cancer-associated neuropathic pain
- Authors
- Chung, Kunho; Ko, Hyoung-Gon; Yi, Yujong; Chung, Seong-Eun; Lim, Jaeyeoung; Park, Seongjun; Pyun, Seon-Hong; Ullah, Irfan; Lee, Jongkil; Kaang, Bong-Kiun; Lee, Sang-Kyung
- Issue Date
- Jul-2024
- Publisher
- 한국약제학회
- Keywords
- Cancer-associated neuropathic pain; Intranasal delivery; NMDA receptor; siNR2B; RVG9R peptide
- Citation
- Journal of Pharmaceutical Investigation, v.54, no.4, pp 483 - 495
- Pages
- 13
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- Journal of Pharmaceutical Investigation
- Volume
- 54
- Number
- 4
- Start Page
- 483
- End Page
- 495
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/194926
- DOI
- 10.1007/s40005-024-00667-w
- ISSN
- 2093-5552
2093-6214
- Abstract
- PurposeThis study aimed to reduce cancer-associated pain by blocking pain signals through the intranasal administration of siRNA targeting the NMDA subunit NR2B (siNR2B).MethodsCancer pain models were established by injecting 3 x 105 B16F10 melanoma cells into the left hind paws of C57BL/6 mice. To evaluate pain reduction, 600 pmol of siNR2B was complexed with the RVG9R peptide at a 20:1 molar ratio, or 5 mg/kg NR2B receptor antagonist Ro25-6981 was used as a positive control. Melanoma-xenografted mice were intranasally administered the peptide/siRNA complex or intraperitoneally inoculated with Ro25-6981 three times a week for 3 weeks. The mechanical withdrawal threshold was determined using an electronic von Frey apparatus.ResultsThe therapeutic effect of intranasally administered siNR2B was observed 21 days after cancer cell implantation in a hind paw melanoma model. NR2B expression in the cancer model was approximately twice that in the normal animals. The groups treated with siNR2B or Ro25-6981 exhibited approximately 60 and 50% of NR2B expression in the thalamus, respectively. This reduced pain signaling in the thalamic region, as evidenced by a decrease in phosphorylated extracellular signal-regulated kinase. In addition, the siNR2B-treated group displayed significant behavioral improvements, a marked reduction in cancer-induced pain, compared with controls. siNR2B treatment in a cancer-induced murine model did not affect the general cognitive function.ConclusionThis study demonstrated that the intranasal delivery of siNR2B in a murine model effectively reduced cancer-induced neuropathic pain by downregulating overexpressed NMDA receptor-mediated pain signaling in the thalamus.
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