Neuropeptides and steroid hormones in arthritis.
Primary afferent nociceptive and peptidergic efferent nerves are sensitized in arthritis and thus easily stimulated by mechanical and chemical stimuli. This leads to increased or disturbed release of neuropeptides from nerve terminals. This local (at the site of stimulation), expanded (expanded and additional receptive fields), and remote (cross-spinal reflexes) neuropeptide release leads to disturbed tissue homeostasis and neurogenic inflammation. In arthritis, raised levels of neuropeptides were detected in the synovial fluid, whereas nerve fibers were lacking in the synovial tissue. It has been hypothesized that cycles of nerve fiber destruction and degeneration follow the cycles of joint inflammation. This evidence suggests that the peripheral nervous system, through its neuropeptides, may contribute to the generation of inflammation, i.e., "neurogenic inflammation." Altered hypothalamic-pituitary-adrenocortical axis function and sex hormone status have been suggested to contribute to the development and persistence of arthritis. In particular, current evidence indicates that glucocorticoid secretion is closely and reciprocally interrelated with inflammation, and that an adrenal insufficiency is present in many forms of immune-mediated arthritis. Conversely, gonadal steroids seem to play a central role as predisposing factors in many forms of arthritis, with estrogens involved as immuno-enhancing hormones and androgens as natural immunosuppressors. Functional receptors for sex hormones have been described in cells involved in the immune response and, after activation, the hormone-receptor complex might modulate the expression of selected cytokines. The possibility of targeting the efferent nerves with specific peptides and replacement therapies with selected steroid hormones may represent a new and potentially efficient and natural system of modulation of the arthritis.
Cerinic
M M
MM
University of Florence, Department of Medicine, Firenze, Italy.
Konttinen
Y
Y
Generini
S
S
Cutolo
M
M
D000818:Animals; D001168:Arthritis / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D001169:Arthritis, Experimental / Q000209:etiology / Q000503:physiopathology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008297:Male; D009479:Neuropeptides / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D010525:Peripheral Nerves / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011247:Pregnancy; D013256:Steroids / Q000502:physiology*; D013373:Substance P / Q000502:physiology
D012739:Gonadal Steroid Hormones; D009479:Neuropeptides; D013256:Steroids; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide