Evidence for neurogenic transmission inducing degenerative cartilage damage distant from local inflammation

Objective. To investigate involvement of the nervous system in ipsilateral and contralateral joint inflammation. Methods. Freund's complete adjuvant (CFA; 1 mg or 1 mu g) was injected unil aterally and the messages (a) from the hind paw to the ipsilateral and cont ralateral knees and (b) from one knee to the contralateral knee were analyz ed. The degenerative impact of the local injury on distant cartilage was as sessed using patellar proteoglycan synthesis as an indicator. Neurogenic me chanisms were blocked either by spinal cord compression or by injection of neurokinin 1 (NK-1) antagonist, or they were mimicked by intraarticular inj ection of substance P, The data were compared with those gathered in a mode l of systemic inflammation, characterized by fever and serum interleukin-6 production. Results, After unilateral subcutaneous injection of CFA, proteoglycan anabo lism decreased bilaterally. Spinal cord compression and administration of t he NK-1 antagonist inhibited the response in the contralateral limb. Follow ing 1 mg CFA subcutaneous injection, the ipsilateral response implicated bo th neurogenic and systemic mechanisms, whereas the nervous system alone was implicated after 1 mu g subcutaneous CFA injection. The 1 mu g CFA intraar ticular injection induced a degenerative contralateral signal, which was ab olished by spinal cord compression and by pretreatment with the NK-1 antago nist. Intraarticular injection of 1 mu g CFA also induced an ipsilateral in crease of anabolism, which was enhanced by spinal cord compression. Similar results were obtained after intraarticular injections of substance P, Thes e effects were not reproduced with turpentine treatment, a systemic model, in which spinal cord compression had no effect. Conclusion. A unilateral inflammation can induce, by neurogenic mechanisms, distal bilateral degeneration of articular cartilage, implicating involvem ent of neuropeptides.