Experimental lumbar radiculopathy immunohistochemical and quantitative demonstrations of pain induced by lumbar nerve root irritation of the rat

Objective. A s&i'ifis of experiments were designed lo 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 rool trauma ana evaluated the ability or the model to effect symptoms and begin to understand the underlying rteurochemical and neuraphyslologic 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 bh Experimental lumbar radiculopathy. Methods, Two basic approaches to nerv*d trauma were considered, direct damage lo the ner^e vie 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 netve root entrap men I, 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 Joose ligatures of 4-0 silk were placed around the nerve roots; 41 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 an pieces of 4-0 chromic gut were laid adjacent to the nerve roois and secured by two loose ligatures of 4-0 chromic gut, ANOVA techniques were used to test for differential effects across time for tho five treatment groups in terms of animal function and biochemistry In the DRG. Results. Rats treated with chromic gut ligature in large quantity demonstrated diffarenllal patterns of re- suits on the injured and noninjured sidas consistent with a lumbar radiculopathy. The injured side demonstrated significant/worse thermal hyperalgesia related to neuropathic pain (P < 0.0001); initial mechanical hy- poalgesia (P<. 001), and motor dysfunction [P <. 001) resolving within 2 weeks; significantly increased c-fes counts (P< -0001) 2 weeks postoperative! which showed a consistent trend toward baseline and return to baseline by 12 weeks; aign'ficantly greater and highly increased VIP concentrations in the dorsal root ganglia 2 weeks pcs;operatively (P <. DM1) 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 postttperatrvely that dia resolve to baseline until a 12-waek 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 undo Hying neuroehemir.al processes Is suggested. Conclusions. Whon the same a parent conditions can be demonstrated in some situations ta be causing pain and in other situations to be Indupgndent of pain, some additional factor or factors nm 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 conse-quences of the pathology, To help unravel the patho- rnechanisms related tD the clinical symptoms, especially pa:n, there is ? need for an experiments! model of lumbar radiculopathy. Therefore, an attempt wes made to model the kind of problem neary to stimulate a clinically relevant nerve rool trauma and to estimate behavioral and functional parameters. The animal model of lumbar radiculopathy described and successfully evaluated in this study shows great promise as a vehicle for both explaining the injury and repair proeasa and facilitating treatment modalities to curtail the injury process and speed repair.