Immunohistochemical and Quantitative Demonstrations of Pain Induced by Lumbar Nerve Root Irritation of the Rat

OBJECTIVE: A series of experiments were designed to develop and validate an animal model of lumbar radiculopathy. More specifically, these investigations introduced a model of chronic neuropathic pain in the rat associated with clinically relevant lumbar nerve root trauma and evaluated the ability of the model to effect symptoms and begin to understand the underlying neurochemical and neurophysiologic factors associated with these neurologic abnormalities. SUMMARY OF BACKGROUND DATA: A search of the literature suggested that these studies were a first attempt to distinguish and elucidate an experimental lumbar radiculopathy. METHODS: Two basic approaches to nerve trauma were considered, direct damage to the nerve via compression, and introduction of foreign materials in proximity to the nerve root that might cause irritation and inflammation leading to chronic symptoms. Ligature around the nerve (i.e., surrounding the nerve with a suture) was considered a plausible irritant that might behave in an animal model in a similar way that nerve root entrapment, often observed in HNP and stenosis cases, might function in humans. Further, varying levels of irritation was modeled by using 4-0 silk as a mild and 4-0 chromic gut as a more harsh irritant. STUDY DESIGN: Five distinct treatments of the nerve roots were investigated initially: 1) a sham intervention, where the surgery simply exposed the nerve roots and dorsal root ganglion followed by standard closing procedures; 2) nerve root clipping, where the nerve roots were clipped with a microhemoclip; 3) 4-0 silk ligature, where two loose ligatures of 4-0 silk were placed around the nerve roots; 4) 4-0 chromic gut 1, where one loose ligature of 4-0 chromic gut was placed around the nerve roots; and 5) 4-0 chromic gut 2, where four 0.3 cm pieces of 4-0 chromic gut were laid adjacent to the nerve roots and secured by two loose ligatures of 4-0 chromic gut. ANOVA techniques were used to test for differential effects across time for the five treatment groups in terms of animal function and biochemistry in the DRG. RESULTS: Rats treated with chromic gut ligature in large quantity demonstrated differential patterns of results on the injured and noninjured sides consistent with a lumbar radiculopathy. The injured side demonstrated significantly worse thermal hyperalgesia related to neuropathic pain (P < 0.0001); initial mechanical hypoalgesia (P < .001), and motor dysfunction (P < .001) resolving within 2 weeks; significantly increased c-fos counts (P < .0001) 2 weeks postoperatively, which showed a consistent trend toward baseline and return to baseline by 12 weeks; significantly greater and highly increased VIP concentrations in the dorsal root ganglia 2 weeks postoperatively (P < .0001) that did not resolve or tend towards baseline after 12 weeks of follow-up in conjunction with a trend toward VIP depletion in the spinal cord 2 weeks postoperatively that did resolve to baseline until a 12-week concentration indicated a significant increase in concentration (P < .002). Quantitative and qualitative changes in c-fos and VIP, correlated with the patterns of behavior and function. Thus, for the first time, evidence to link outcome behaviors and function with underlying neurochemical processes is suggested. CONCLUSIONS: When the same apparent conditions can be demonstrated in some situations to be causing pain and in other situations to be independent of pain, some additional factor or factors not considered in the original investigations may be mediating the outcome. Neurochemical consequences of nerve root irritation provide a theoretical framework for hypothesizing about various types of mediating events that might explain how similar apparent pathology might reasonably lead to different predictions about behavior consequences of the pathology.(ABSTRACT TRUNCATED AT 400 WORDS)