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

Background Diabetes mellitus and the associated neuropathic complications have become a steadily increasing global health burden. Diabetic patients are estimated to require surgery at least twice as often as nondiabetic patients. Neuropathy may change the way nerves respond to nerve blocks. There is currently no consensus on whether regional anaesthesia techniques should be adopted in these patients. Long-acting local anaesthetics ( e.g . bupivacaine HCl) or sustained-release formulations of bupivacaine ( e.g . liposomal bupivacaine) could prove neurotoxic in the presence of diabetic neuropathy. The aim of the study was to assess neurotoxicity of liposome bupivacaine in streptozotocin (STZ)-induced diabetic mice after sciatic nerve block using a reduction in fibre density and decreased myelination assessed by G-ratio as an indicator of local anaesthetic neurotoxicity. Results Prior to performing sciatic nerve block, higher levels of fasting glucose were recorded in diabetic mice compared to nondiabetic mice ( P < 0.001). Likewise, significant differences were noted in the tail flick and plantar test thermal latencies between the groups ( P < 0.001) which confirmed the presence of peripheral sensory neuropathy in diabetic mice. In both, diabetic and nondiabetic mice, sciatic nerve block with 0.25% bupivacaine HCl resulted in a significantly greater G-ratio (axon diameter/large fibre diameter) and an axon diameter compared to nerves treated with 1.3% liposomal bupivacaine or saline (0.9% sodium chloride) ( P < 0.01 ). Moreover, sciatic nerve block with 0.25% bupivacaine HCl resulted in higher fibre density and 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 Under the conditions of this study, sciatic nerve block with bupivacaine HCl, but not liposome bupivacaine or saline, resulted in histomorphometric indices of neurotoxicity. The presence of diabetes did not appear to affect the severity of the histologic findings.