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Updated: Mar 9, 2026
Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
miR-15b mediates oxaliplatin-induced chronic neuropathic pain through BACE1 down-regulation
Naomi Ito1,2, Atsushi Sakai1, Noriko Miyake3
1Department of Pharmacology, Nippon Medical School, Tokyo, Japan.
Background And Purpose:
Although oxaliplatin is an effective anti-cancer platinum compound, it can cause painful chronic neuropathy, and its molecular mechanisms are poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Although miRNAs have been increasingly recognized as important modulators in a variety of pain conditions, their involvement in chemotherapy-induced neuropathic pain is unknown.
Experimental Approach:
Oxaliplatin-induced chronic neuropathic pain was induced in rats by i.p. injections of oxaliplatin (2 mg·kg-1 ) for five consecutive days. The expression levels of miR-15b and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1 also known as β-secretase 1) were examined in the dorsal root ganglion (DRG). To examine the function of miR-15b, an adeno-associated viral vector encoding miR-15b was injected into the DRG in vivo.
Key Results:
Among the miRNAs examined in the DRG in the late phase of oxaliplatin-induced neuropathic pain, miR-15b was most robustly increased. Our in vitro assay results determined that BACE1 was a target of miR-15b. BACE1 and miR-15b were co-expressed in putative myelinated and unmyelinated DRG neurons. Overexpression of miR-15b in DRG neurons caused mechanical allodynia in association with reduced expression of BACE1. Consistent with these results, a BACE1 inhibitor dose-dependently induced significant mechanical allodynia.
Conclusions And Implications:
These findings suggest that miR-15b contributes to oxaliplatin-induced chronic neuropathic pain at least in part through the down-regulation of BACE1.
Insights
MicroRNAs (miRNAs) like miR-15b are involved in oxaliplatin-induced neuropathic pain. Upregulation of miR-15b in the dorsal root ganglion leads to pain by down-regulating BACE1.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Oxaliplatin is an effective chemotherapy drug but causes painful neuropathy.
- The molecular mechanisms underlying oxaliplatin-induced neuropathic pain are not well understood.
- MicroRNAs (miRNAs) regulate gene expression and are implicated in pain, but their role in chemotherapy-induced pain is unknown.
Purpose of the Study:
- To investigate the role of specific microRNAs (miRNAs) in oxaliplatin-induced neuropathic pain.
- To identify the molecular targets of relevant miRNAs in the dorsal root ganglion (DRG).
Main Methods:
- Oxaliplatin-induced neuropathic pain was modeled in rats.
- Expression levels of miR-15b and BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1) were measured in the DRG.
- An adeno-associated viral vector was used to overexpress miR-15b in the DRG.
Main Results:
- miR-15b expression was significantly increased in the DRG during oxaliplatin-induced neuropathic pain.
- BACE1 was identified as a direct target of miR-15b.
- Overexpression of miR-15b in DRG neurons induced mechanical allodynia (pain hypersensitivity) and reduced BACE1 expression.
- Inhibition of BACE1 also resulted in mechanical allodynia.
Conclusions:
- miR-15b plays a significant role in the development of oxaliplatin-induced chronic neuropathic pain.
- The mechanism involves the down-regulation of BACE1 by miR-15b in DRG neurons.
- These findings identify a novel miRNA-mediated pathway contributing to chemotherapy-induced pain.
