Increases in the levels of proinflammatory
cytokines, such as
TNF alpha, have been intricately linked with
arthritis and the pathogenesis of several models of
neuropathic pain. In addition,
arthritis (as well as other types of persistent
pain) is associated with increased sympathetic activity and alterations of other responses in autonomic nervous activity.
Adrenergic regulation of LPS-stimulated TNF production by M phi isolated from rats with streptococcal-cell-wall (SCW)-induced
arthritis has been examined. Serum TNF levels and the cellular composition of peritoneal exudates have also been assessed. M phi were obtained from: (1) normal control rats, (2) animals injected with complete
Freund's adjuvant (CFA), 3 rats injected with SCW and arthritic, and (4) those injected with SCW, which failed to develop
arthritis. Serum levels of
TNF alpha in rats that develop
arthritis are significantly greater (2.4 fold) than levels from the other groups. The proportion of OX19-positive T cell subpopulations are the same in peritoneal exudates from all groups. Immunocytochemical staining also reveals differences between M phi subgroups in the degree of activation. Peritoneal exudates from rats that develop
arthritis contain a greater proportion of the high TNF producing subclass of M phi, as identified by positive ED3 staining (p < 0.001). In contrast,
Ia antigen presenting M phi (OX6-positive) in the peritoneal exudate cells are only elevated in rats administered CFA. The selective blockade of
adrenergic receptors by
idazoxan or
propranolol demonstrates that the constitutive involvement of either alpha 2 or beta-
adrenergic regulation of M phi-derived TNF production is pronounced in rats with
arthritis (p < 0.001). These investigations demonstrate a distinctive pattern of peripheral M phi populations in rats that develop chronic polyarthritic
pain. We believe that identification of interactions between the
adrenergic responses and proinflammatory
cytokines will lead to the development of improved strategies to treat patients with
chronic pain.