title: Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy.
abstract: Nerve injury leads to central neuroimmunologic responses that may be integral to the development and maintenance of chronic neuropathic pain in humans. Recent data have demonstrated that cytokines and growth factors may be strongly implicated in the generation of pain states at both peripheral and central nervous system sites. We utilized immunohistochemical methods to investigate this phenomenon in rat models of neuropathic pain. Specifically, we employed well-characterized models of neuropathy that result in behaviors suggestive of neuropathic pain in humans; a freeze lesion of the sciatic nerve, termed sciatic cryoneurolysis, and a chronic constriction sciatic nerve injury. We used immunohistochemistry to examine spinal localization of the cytokines, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and the growth factors, basic fibroblast growth factor (bFGF), and transforming growth factor-beta1 (TGF-beta) at 3, 14, and 35 days following sciatic cryoneurolysis or 6 days following chronic constriction injury as compared with normal, unoperated rats. There was minimal, diffuse cytokine/growth factor staining in lumbar spinal tissue from the normal group. However, cell profile quantification demonstrated increases in lumbar spinal IL-1beta-, TNF-alpha- and TGF-beta-like immunoreactivity (LI) in both mononeuropathy models studied. At 3 days following sciatic cryoneurolysis, intense bFGF LI was present in the ipsilateral dorsal and ventral horn. By 14 days bFGF LI was also observed in contralateral dorsal and ventral horns. In contrast, we found no obvious staining differences in lumbar spinal cord following the chronic constriction injury. This study demonstrated increased specific cytokine and growth factor-like expression in the spinal cord following peripheral nerve injuries. It also showed a differential expression of bFGF in two distinct mononeuropathy models. These results provide further evidence that central cytokine production via a neuroimmune cascade may be involved in the development and maintenance of behaviors that mimic neuropathic pain following nerve injury.
authors.affiliation: Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. joyce.a.deleo@dartmouth.edu
authors.forename: J A
authors.initials: JA
authors.lastname: DeLeo
authors.forename: R W
authors.initials: RW
authors.lastname: Colburn
authors.forename: A J
authors.initials: AJ
authors.lastname: Rickman
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005615:Freezing; D006133:Growth Substances / Q000378:metabolism*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D009408:Nerve Compression Syndromes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012584:Sciatic Nerve / Q000293:injuries*; D013116:Spinal Cord / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism*
chemical_list: D016207:Cytokines; D006133:Growth Substances; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2