Sympathetic nervous system in chronic joint pain.

pain Sir: We read with interest the recent review by Dr Kidd and colleagues on the role of the sympathetic nervous system in chronic joint pain and inflammation.' The authors suggest, on the one hand, a continued influence of the sympathetic nervous system on the inflammatory synovium while, on the other hand, they postulate that nerve fibres are destroyed in the synovial membrane in chronic rheumatoid arthritis. Based on a study of synovial membrane obtained from patients with rheumatoid arthritis undergoing arthroplasty the authors argue that a reduction in immunostaining for the neuronal marker PGP 9 5, in addition to reduced neuropeptide immunoreactivity as previously described,2 favours destruction of nerve fibres over neuronal depletion. In a similar study, Gronblad et al examined nerve fibres and neuropeptide immunoreactivity in rheumatoid synovium collected at synovectomy and arthroplasty.3 In this study seven of nine patients showed reduced immunoreactivity for neuropeptides but well marked stromal immunoreactivity for nerve fibres. Further evidence for increased release of neuropeptide and subsequent depletion of neuronal stores is provided by the following observations. In a recent case report4 we studied synovial membrane and fluid in a patient with psoriatic arthritis of the knee, in whom sparing of the contralateral side occurred owing to previous hemiplegia. We noted reduced immunoreactivity for synovial membrane substance P in the clinically inflamed joint, in addition to raised levels of substance P in the synovial fluid, while in the contralateral non-inflamed joint there was marked immunoreactivity for synovial membrane substance P but undetectable synovial fluid levels. Immunoreactivity of nerve fibres was demonstrated equally in both specimens. These observations suggest that substance P is released from nerve fibres into the synovial fluid in the inflamed joint. Finally, synovial fluid substance P levels have been measured in a number of different arthropathies.5 In all groups with arthritis higher levels were reported in synovial fluid than in plasma. The role of neuropeptide in the inflammatory synovium is not clear. Interestingly, neuropeptides have been shown to activate rheumatoid synoviocytes' and to cause production of inflammatory cytokines by human monocytes.7 We agree with the authors that the role of these substances within the rheumatoid joint leads to a promotion of the inflammatory response. The evidence herein suggests, however, that depletion of neuropeptide in inflammatory synovium is more probably due to increased release into the synovial fluid rather than destruction of nerve fibres as suggested. Substance P-, calcitonin gene-related peptide-and …