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. 2021 Oct 15;134(1):204–215. doi: 10.1213/ANE.0000000000005768

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Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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Figure 1. — Overexpression of neuronal GRK2 in spinal cord–alleviated cisplatin-induced peripheral neuropathy. A, Western blot analysis of GRK2 after 5 injections of cisplatin. Results are normalized to β-actin and shown as ratios to saline-treated mice. Values are mean ± SEM. *P < .05, P = .0259. B, Experimental strategy for neuronal GRK2 overexpression. Neuron-specific promoter hSyn targeted Cre-ERT2 recombination activated by tamoxifen. C, Tamoxifen-activated Cre-ERT2 upregulated the expression of GRK2 in the spinal cord. Results are normalized to β-actin. Values are mean ± SEM. *P < .05, P = .0334. D, Representative images show NeuN labeling (red) and eGFP-tagged (green) AAV-GRK2 in the spinal cord. Scale bar, 100 μm. E, Upregulation of neuronal GRK2 prevented cisplatin-induced reduction of PWT. Values are mean ± SEM. *P < .05, **P < .01. Saline versus cisplatin P = .0011; cis + AAV-eGFP versus cis + AAV-GRK2 P = .0198; cisplatin versus cis + AAV-GRK2 P = .0024. F, Upregulation of neuronal GRK2 shortened cisplatin-induced prolonged responsive time. Values are mean ± SEM. *P < .05, **P < .01. Saline versus cisplatin P = .0016; cis + AAV-eGFP versus cis + AAV-GRK2 P = .0178; cisplatin versus cis + AAV-GRK2 P = .0014. G, Immunofluorescence staining of PGP 9.5 positive nerve fibers (white arrow) in the hind paw (scale bar =100 mm). H, Upregulation of neuronal GRK2 inhibited cisplatin-induced IENFs loss. Values are mean ± SEM. **P < .01, ***P < .001. Saline versus cisplatin P = .0027; cis + AAV-eGFP versus cis + AAV-GRK2 P = .0002; cisplatin versus cis + AAV-GRK2 P = .0004. AAV indicates adeno-associated virus; Cre-ERT2, cyclization recombinase estrogen receptor tamoxifen 2; eGFP, enhanced green fluorescent protein; GRK2, G protein–coupled receptor kinase 2; hSyn, human synapsin; IENFs, intraepidermal nerve fibers; NeuN, neuronal nuclei; PCR, polymerase chain reaction; PGP, protein gene product; PWT, paw withdrawal threshold; SEM, standard error of the mean; WB, Western blot.