Assessment of functional and behavioral changes sensitive to painful disc degeneration

Abstract

The development of an in vivo rodent discogenic pain model can provide insight into mechanisms for painful disc degeneration. Painful disc degeneration in rodents can be inferred by examining responses to external stimuli, observing pain-related behaviors, and measuring functional performance. This study compared the sensitivity of multiple pain and functional assessment methods to disc disruption for identifying the parameters sensitive to painful disc degeneration in rats. Disc degeneration was induced in rats by annular injury with saline injection. The severity of disc degeneration, pain sensitivity, and functional performance were compared to sham and näve control rats. Saline injection induced disc degeneration with decreased disc height and MRI signal intensity as well as more fibrous nucleus pulposus, disorganized annular lamellae and decreased proteoglycan. Rats also demonstrated increased painful behaviors including decreased hindpaw mechanical and thermal sensitivities, increased grooming, and altered gait patterns with hindpaw mechanical hyperalgesia and duration of grooming tests being most sensitive. This is the first study to compare sensitivities of different pain assessment methods in an in vivo rat model of disc degeneration. Hindpaw mechanical sensitivity and duration of grooming were the most sensitive parameters to surgically induced degenerative changes and overall results were suggestive of disc degeneration associated pain.

Annular puncture with tumor necrosis factor-alpha injection enhances painful behavior with disc degeneration in vivo

“…Rat models have been widely used for studying discogenic pain because the pain associated with disc injury can be assessed with various measurement techniques [18–29]. Most animal studies on disc degeneration and pain have investigated the pathophysiology of disc herniation and radicular pain following posterolateral annular puncture with herniated NP [23,30] or nerve root compression with NP materials from caudal discs [26–28,31].…”

“…It revealed a need for developing an in vivo rat model with more chronic painful disc degeneration. More recently, an anterior puncture with saline injection into three adjacent discs in the lumbar spine demonstrated repeatable disc degeneration and increased pain sensitivity without evidence for herniation [29]. …”

Looking beyond the intervertebral disc: the need for behavioral assays in models of discogenic pain

“…In this example, IVD degeneration was induced using anterior puncture and injection as described previously. 20 Both animals had a reduced mechanical paw-withdrawal threshold immediately following injury, illustrating that IVD injury and degeneration can induce painful conditions. However, the paw-withdrawal threshold of one rat slightly recovered 2 weeks postsurgery, while a low threshold was maintained in the other rat throughout the 6-week experiment.…”

“…The use of rodent models is further supported by the existence of validated practical assays for probing pain. 20 …”

“…Degeneration accumulates in human IVDs over many years and usually exhibits dehydration of the NP, 19 disorganization of the AF lamellae, 19 undistinguished NP–AF boundary, 19 defects in the endplates, 17 and a loss of IVD height. 20 Degenerated IVDs may also develop annular fissures, 17 which can lead to NP herniation and CEP injury. In the degenerated IVD, the balance between anabolism and catabolism is lost.…”