Fibromyalgia (FM) is characterized by chronic generalized pain as the main symptom, with extreme fatigue, insomnia and depression as secondary symptoms. Clinical studies have indicated the presence of psychological stress, sympathetic nervous system hyperexcitation and immune system abnormalities, as a trigger for the onset of the disease, but the contribution to the pathogenesis of the disease remains unclear. Here, we employed the repeated acid saline-induced generalized pain (AcGP) model, as an experimental mouse model of FM. In this model, the unilateral repeated acid injection into gastrocnemius muscle induced transient and long-lasting mechanical allodynia. We focused on the spleen, a secondary lymphoid organ, and found that the intravenous treatments of splenocytes derived from mice treated with AcGP caused allodynia in naive mice. Since the spleen is directly innervated by sympathetic nerve, we examined whether adrenergic receptors are necessary for pain development or maintenance. The administration of butoxamine, a selective β₂-blocker, prevented the development but did not reverse the maintenance of pain-like behavior in AcGP mice. Furthermore, β₂-blockade in donor AcGP mice eliminated pain reproduction in recipient mice injected with AcGP splenocytes. These results suggest that sympathetic β₂ signaling is enhanced by physical/psychological stress, and that immune system cells in the spleen activated in response play an important role in the formation and maintenance of chronic pain. Currently, another model of FM, the intermittent psychological stress-induced generalized pain (IPGP) model, is being used to investigate the detailed mechanisms of this signaling.