Neurotoxicity of bupivacaine and liposome bupivacaine after sciatic nerve block in healthy and streptozotocin-induced diabetic mice

Markova, Liljana (author), Umek, Nejc (author), Horvat, Simon (author), Hadžić, Admir (author), Kuroda, Maxine M. (author), Stopar Pintarič, Tatjana (author), Mrak, Vesna (author), Cvetko, Erika (author)

Background: Long-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when applied in the setting of diabetic neuropathy. The aim of the study was to assess neurotoxicity of bupivacaine and liposome bupivacaine in streptozotocin (STZ) - induced diabetic mice after sciatic nerve block. We used the reduction in fibre density and decreased myelination assessed by G-ratio (defined as axon diameter divided by large fibre diameter) as indicators of local anaesthetic neurotoxicity. Results: Diabetic mice had higher plasma levels of glucose (P < 0.001) and significant differences in the tail flick and plantar test thermal latencies compared to healthy controls (P < 0.001). In both diabetic and nondiabetic mice, sciatic nerve block with 0.25% bupivacaine HCl resulted in a significantly greater G-ratio and an axon diameter compared to nerves treated with 1.3% liposome bupivacaine or saline (0.9% sodium chloride) (P < 0.01). Moreover, sciatic nerve block with 0.25% bupivacaine HCl resulted in lower fibre density and higher large fibre and axon diameters compared to the control (untreated) sciatic nerves in both STZ-induced diabetic (P < 0.05) and nondiabetic mice (P < 0.01). No evidence of acute or chronic inflammation was observed in any of the treatment groups. Conclusions: In our exploratory study the sciatic nerve block with bupivacaine HCl (7 mg/kg), but not liposome bupivacaine (35 mg/kg) or saline, resulted in histomorphometric indices of neurotoxicity. Histologic findings were similar in diabetic and healthy control mice.

• Language: English
• Keywords: bupivacaine hydrochloride, diabetes, neurotoxicity, liposome bupivacaine injectable suspension, peripheral neuropathy
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 8 str.
• Numbering: Vol. 16, art. 247
• PID: 20.500.12556/RUL-128775
• UDC: 615.2
• ISSN on article: 1746-6148
• DOI: 10.1186/s12917-020-02459-4
• COBISS.SI-ID: 23004675
• Publication date in RUL: 28.07.2021

Record is a part of a journal

• Title: BMC veterinary research
• Publisher: Springer Nature
• ISSN: 1746-6148
• COBISS.SI-ID: 515674393

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 17.07.2020

Secondary language

• Language: Slovenian
• Keywords: bupivakain hidroklorid, diabetes, nevrotoksičnost, injicirana suspenzija liposomskega bupivakaina, periferalna nevropatija