Comparison of sensory tests and neuronal quantity of peripheral nerves between streptozotocin (STZ)-induced diabetic rats and paclitaxel (PAC)-treated rats

Abstract

Although diabetic peripheral neuropathy (DPN) and chemotherapy-induced peripheral neuropathy (CIPN) are different disease entities, they share similar neuropathic symptoms that impede quality of life for these patients. Despite having very similar downstream effects, there have been no direct comparisons between DPN and CIPN with respect to symptom severity and therapeutic responses. We compared peripheral nerve damage due to hyperglycemia with that caused by paclitaxel (PAC) treatment as represented by biochemical parameters, diverse sensory tests, and immunohistochemistry of cutaneous and sciatic nerves. The therapeutic effects of alpha-lipoic acid and DA-9801 were also compared in the two models. Animals were divided into seven groups (n = 7–10) as follows: normal, diabetes (DM), DM + alpha-lipoic acid 100 mg/kg (ALA), DM + DA-9801 (100 mg/kg), paclitaxel-treated rat (PAC), PAC + ALA (100 mg/kg), and PAC + DA-9801 (100 mg/kg). The sensory thresholds of animals to mechanical, heat, and pressure stimuli were altered by both hyperglycemia and PAC when compared with controls, and the responses to sensory tests were different between both groups. There were no significant differences in the biochemical markers of blood glutathione between DM and PAC groups (p > .05). Quantitative comparisons of peripheral nerves by intraepidermal nerve fiber density (IENFD) analysis indicated that the DM and PAC groups were similar (6.18 ± 1.03 vs. 5.01 ± 2.57). IENFD was significantly improved after ALA and DA-9801 treatment in diabetic animals (7.6 ± 1.28, 7.7 ± 1.28, respectively, p < .05) but did not reach significance in the PAC-treated groups (6.05 ± 1.76, 5.66 ± 1.26, respectively, p > .05). Sciatic nerves were less damaged in the PAC-treated groups compared with the DM groups with respect to axonal diameter and area (8.60 ± 1.14 μm vs. 6.66 ± 1.07 μm, and 59.04 ± 15.16 μm² vs. 35.71 ± 11.2 μm², respectively, p < .05). Based on these results, the neuropathic manifestation and therapeutic responses of DPN may be different from other peripheral neuropathies. Therefore, specific pathogenic consideration according to peripheral neuropathy classification in addition to common treatments needs to be developed for management strategies of peripheral neuropathies.

Keywords:

• Diabetes
• IENFD
• paclitaxel
• peripheral neuropathy

Acknowledgements

The authors would like to thank the Research Institute of Clinical Medicine of Chonbuk National University—Biomedical Research Institute of Chonbuk National University Hospital for supporting this study through grant funding and access to experimental facilities. The authors would also like to thank Professor Nigel A. Calcutt at UCSD for reviewing this manuscript. Heung Yong Jin and Na Young Lee contributed equally to this manuscript.

Disclosure statement

The authors report no conflicts of interest.