| First Author | Nieto FR | Year | 2014 |
| Journal | Mol Pain | Volume | 10 |
| Pages | 11 | PubMed ID | 24517272 |
| Mgi Jnum | J:225243 | Mgi Id | MGI:5691894 |
| Doi | 10.1186/1744-8069-10-11 | Citation | Nieto FR, et al. (2014) Genetic inactivation and pharmacological blockade of sigma-1 receptors prevent paclitaxel-induced sensory-nerve mitochondrial abnormalities and neuropathic pain in mice. Mol Pain 10:11 |
| abstractText | BACKGROUND: Paclitaxel, a widely-used antineoplastic drug, produces a painful peripheral neuropathy that in rodents is associated with peripheral-nerve mitochondrial alterations. The sigma-1 receptor (sigma1R) is a ligand-regulated molecular chaperone involved in mitochondrial calcium homeostasis and pain hypersensitivity. This receptor plays a key role in paclitaxel-induced neuropathic pain, but it is not known whether it also modulates mitochondrial abnormalities.In this study, we used a mouse model of paclitaxel-induced neuropathic pain to test the involvement of the sigma1R in the mitochondrial abnormalities associated with paclitaxel, by using genetic (sigma1R knockout mice) and pharmacological (sigma1R antagonist) approaches. RESULTS: Paclitaxel administration to wild-type (WT) mice produced cold- and mechanical-allodynia, and an increase in the frequency of swollen and vacuolated mitochondria in myelinated A-fibers, but not in C-fibers, of the saphenous nerve. Behavioral and mitochondrial alterations were marked at 10 days after paclitaxel-administration and had resolved at day 28. In contrast, paclitaxel treatment did not induce allodynia or mitochondrial abnormalities in sigma1R knockout mice. Moreover, the prophylactic treatment of WT mice with BD-1063 also prevented the neuropathic pain and mitochondrial abnormalities induced by paclitaxel. CONCLUSIONS: These results suggest that activation of the sigma1R is necessary for development of the sensory nerve mitochondrial damage and neuropathic pain produced by paclitaxel. Therefore, sigma1R antagonists might have therapeutic value for the prevention of paclitaxel-induced neuropathy. |
