EXPERIMENTAL LUMBAR RADICULOPATHY - 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 valida te an animal model of lumbar radiculopathy. More specifically, these i nvestigations intro duced a model of chronic neuropathic pain in the r at associated with clinically relevant lumbar nerve root trauma and ev aluated the ability of the model to effect symptoms and begin to under stand the underlying neurochemical and neurophysiologic factors associ ated with these neurologic abnormalities. Summary of Background Data. A search of the literature suggested that these studies were a first a ttempt to distinguish and elucidate an experimental lumbar radiculopat hy. Methods. Two basic approaches to nerve trauma were considered, dir ect damage to the nerve via compression, and introduction of foreign m aterials in proximity to the nerve root that might cause irritation an d 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 n erve 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 irrita nt. Study Design. Five distinct treatments of the nerve roots were inv estigated 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 l igatures of 4-0 silk were placed around the nerve roots; 4) 4-0 chromi c 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 o f 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 grou ps in terms of animal function and biochemistry in the DRG. Results. R ats treated with chromic gut ligature in large quantity demonstrated d ifferential patterns of results on the injured and noninjured sides co nsistent with a lumbar radiculopathy. The injured side demonstrated si gnificantly worse thermal hyperalgesia related to neuropathic pain (P < 0.0001); initial mechanical hypoalgesia (P < .001), and motor dysfun ction (P < .001) resolving within 2 weeks; significantly increased c-f os counts (P < .0001) 2 weeks postoperatively, which showed a consiste nt trend toward baseline and return to baseline by 12 weeks; significa ntly greater and highly increased VIP concentrations in the dorsal roo t 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 postoperativel y 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 outc ome behaviors and function with underlying neurochemical processes is suggested. Conclusions. When the same apparent conditions can be demon strated in some situations to be causing pain and in other situations to be independent of pain, some additional factor or factors not consi dered in the original investigations may be mediating the outcome. Neu rochemical consequences of nerve root irritation provide a theoretical framework for hypothesizing about various types of mediating events t hat might explain how similar apparent pathology might reasonably lead to different predictions about behavior consequences of the pathology . To help unravel the pathomechanisms related to the clinical symptoms , especially pain, there is a need for an experimental model of lumbar radiculopathy. Therefore, an attempt was made to model the kind of pr oblem necessary to stimulate a clinically relevant nerve root trauma a nd to estimate behavioral and functional parameters. The animal model of lumbar radiculopathy described and successfully evaluated in this s tudy shows great promise as a vehicle for both explaining the injury a nd repair process and facilitating treatment modalities to curtail the injury process and speed repair.