†These authors contributed equally.
Introduction: Painful diabetic neuropathy (PDN) is an
intractable chronic pain condition affecting a growing number of adults in China.
Spinal cord stimulation (SCS) has been employed in the treatment of PDN for
several decades. However, the efficacy and underlying mechanisms of SCS are still
inconclusive. Methods: In this study, we adopted an implantable pulse
generator to deliver electrical stimulation (50 Hz, 200 us pulse width, 12
hours/day in 5 weeks) via a quadripolar electrode in the lumbar epidural space to
treat pain hypersensitivity in the rat model of PDN. Electronic von Frey and
Hargreaves tests were used to measure the responses to mechanical and heat
stimuli, respectively. Quantitative PCR, western blotting, and enzyme-linked
immunosorbent assay (ELISA) were adopted to explore the changes in
neuroinflammation after SCS. Results: SCS alleviated mechanical
allodynia and heat hyperalgesia over a period of 3 weeks in diabetic rats. SCS
completely suppressed neuropathy-induced Tlr4 and NF