Characterizing a new rat model of chronic pain after spine surgery

Abstract

Chronic pain after spine surgery (CPSS) is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40% of patients undergoing lumbar spine surgery. We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures. Step 1: A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion (DRG) and the spinal nerve, a common cause of low back pain (LBP). Step 2: The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw, followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients. The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy. However, rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw, impaired gait, and reduced spontaneous exploration activity, indicating CPSS. Patch clamp recording revealed a significant augmentation in the intrinsic excitability of small-diameter DRG neurons in CPSS rats. Administration of Dermorphin [D-Arg2, Lys4] (1–4) amide (DALDA, 5 mg /kg, i.p.), a peripherally acting mu-opioid receptor (MOR)-preferred agonist, attenuated pain hypersensitivity, capsaicin-induced [Ca²⁺]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats. Our findings suggest that this new model, which mirrors the nature of CPSS developed in patients, may be useful for future studies of the underlying mechanisms.