2. Academic Validation
  3. Defective autophagy contributes to bupivacaine-induced aggravation of painful diabetic neuropathy in db/db mice

Defective autophagy contributes to bupivacaine-induced aggravation of painful diabetic neuropathy in db/db mice

  • Neuropharmacology. 2023 Dec 15:245:109814. doi: 10.1016/j.neuropharm.2023.109814.
Keke Fan 1,  Qinming Liao 2,  Pengfei Yuan 3,  Rui Xu 4,  Zhongjie Liu 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Shenzhen Children's Hospital, Yantian Road 7019, Shenzhen, 518000, Guangdong Province, China. Electronic address: [email protected].
  • 2 Department of Neurosurgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, Guangdong Province, China. Electronic address: [email protected].
  • 3 Department of Anesthesiology, South China Hospital of Shenzhen University, Fuxin Road 1, ShenZhen, 518116, Guangdong Province, China. Electronic address: [email protected].
  • 4 Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Industrial Avenue Central 253, Guangzhou, 510282, Guangdong Province, China. Electronic address: [email protected].
  • 5 Department of Anesthesiology, Shenzhen Children's Hospital, Yantian Road 7019, Shenzhen, 518000, Guangdong Province, China; Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Industrial Avenue Central 253, Guangzhou, 510282, Guangdong Province, China. Electronic address: [email protected].
PMID: 38104768 DOI: 10.1016/j.neuropharm.2023.109814
Abstract

Current evidence suggests that hyperactivated or impaired Autophagy can lead to neuronal death. The effect of local anesthetics on painful diabetic neuropathy (PDN) and the role of Autophagy in the above pathological process remain unclear, warranting further studies. So, PDN models were established by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in Leptin gene-mutation (db/db) mice. Wild type (WT) and PDN mice received intrathecal 0.75% bupivacaine or/with intraperitoneal drug treatment (rapamycin or bafilomycin A1). Subsequently, the PWT and PWL were measured to assess hyperalgesia at 6 h, 24 h, 30 h, and 48 h after intrathecal bupivacaine. Also, sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) were measured before and 48 h after intrathecal bupivacaine treatment. The spinal cord tissue of L4-L6 segments and serum were harvested to evaluate the change of Autophagy, oxidative stress, oxidative injury, and Apoptosis. We found that bupivacaine induced the activation of Autophagy but did not affect the pain threshold, SNCV and MNCV in WT mice at predefined time points. Conversely, bupivacaine lowered autophagosome generation and degradation, slowed SNCV and aggravated spinal dorsal horn neuron oxidative injury and hyperalgesia in PDN mice. The Autophagy activator (rapamycin) could decrease spinal dorsal horn neuron oxidative injury, alleviate the alterations in SNCV and hyperalgesia in bupivacaine-treated PDN mice. Meanwhile, the Autophagy Inhibitor (bafilomycin A1) could exacerbate spinal dorsal horn neuron oxidative injury, the alterations in SNCV and hyperalgesia in bupivacaine-treated PDN mice. Our results showed that bupivacaine could induce defective Autophagy, slowed SNCV and aggravate spinal dorsal horn neuron oxidative injury and hyperalgesia in PDN mice. Restoring Autophagy may represent a potential therapeutic approach against nerve injury in PDN patients with local anesthesia and analgesia.

Keywords

Anesthetic drugs; Autophagy; Bupivacaine; Diabetes mellitus; Neuropathic pain; Oxidative stress.

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