The Inhibitory Effect of NSAIDs and Opioids on Spinal Fusion: An animal model.

Abstract

Translational Research. To evaluate the relative effects of NSAIDs, opioids, and a combination of the two on spinal fusion inhibition in a rodent model. Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are common postoperative analgesic agents. Since NSAIDs inhibit the cyclooxygenase (COX) pathway they are seldom prescribed following spinal fusion. Opioids may be given instead, but recent evidence suggests opioids also adversely affect spinal fusion quality and success. Eighty male Sprague-Dawley rats underwent L4-5 posterior lumbar fusion and were given one of the following analgesia regimens: saline, morphine (6mg/kg), ketorolac (4mg/kg), or morphine (3mg/kg) and ketorolac (2mg/kg). Serum samples were drawn to evaluate systemic pro-osteoblastic cytokines and vascular endothelial growth factor-A (VEGF-A) levels, which were measured via enzyme-linked immunosorbent assays (ELISA). After six weeks, the rats were sacrificed and the operated spinal segments underwent manual palpation, microCT, and histological analysis. Manual palpation scores were significantly diminished in the opioid, NSAID, and multimodal groups when compared to control (P<0.001). MicroCT fusion scores (P<0.001) and fusion rates (control: 75% vs. NSAID: 35% vs. opioid: 0% vs. combination: 15%, P<0.001) were significantly diminished in the treatment groups. The bone volume (BV) to tissue volume (TV) ratio (BV/TV) (P<0.001) and bone mineral density (BMD) (P<0.001) were all lower in the treatment groups with the opioid and combined groups having the lowest BMD. Although statistically insignificant (P<0.09), the concentration of VEGF-A was greater in the control group compared to opioids, NSAIDs, and the combined group. Opioids and NSAIDs, both independently and combined, inhibited spinal fusion and caused inferior bony callus. Administration of opioids resulted in the lowest rate of spinal fusion. We propose this may be due to the inhibition of VEGF-A, which limits angiogenesis to the burgeoning fusion mass.