Although
chronic pain is the most common symptom of
arthritis, relatively little is known about the mechanisms driving it. Recently, a sprouting of autonomic sympathetic fibers into the upper dermis of the skin, an area that is normally devoid of them, was found in the skin following chronic
inflammation of the rat hindpaw. While this sprouting only occurred when signs of joint and bone damage were present, it remained to be clarified whether it was a consequence of the chronic
inflammation of the skin or of the
arthritis and whether it also occurred in the joint. In the present study, we used a model of
arthritis in which complete
Freund's adjuvant (CFA) was injected into the rat ankle joint. At 4 weeks following CFA treatment, there was an increase in sympathetic and peptidergic fiber density in the ankle joint synovium. We also observed a sympathetic, but not peptidergic, fiber sprouting in the skin over the joint, which may be a consequence of the increased levels of mature
nerve growth factor levels in skin, as revealed by Western blot analysis. The pharmacological suppression of sympathetic fiber function with systemic
guanethidine significantly decreased the
pain-related behavior associated with
arthritis.
Guanethidine completely suppressed the heat
hyperalgesia and attenuated mechanical and
cold hypersensitivity. These results suggest that transmitters released from the sprouted sympathetic fibers in the synovial membrane and upper dermis contribute to the
pain-related behavior associated with
arthritis. Blocking the sympathetic fiber sprouting may provide a novel therapeutic approach to alleviate
pain in
arthritis.