Neuropeptides in experimental and degenerative arthritis.
Classical symptoms of both inflammatory and degenerative arthritides may contribute to neurogenic responses like wheal, flare, edema, and pain. Rheumatoid arthritis (RA) is an autoimmune disease with an immunogenetic background. Neurogenic inflammation has been considered to play an essential role in RA, in part because of the symmetrical involvement (cross-spinal reflexes) and the predominant involvement of the most heavily innervated small joints of the hands and the feet (highly represented in the hominiculus). In contrast, osteoarthritis (OA) is considered to arise as a result of degeneration of the hyaline articular cartilage, which secondarily results in local inflammation and pain. However, it is possible that the age-related and predominant (compared to nociceptive nerves) degeneration of the proprioceptive, kinesthetic and vasoregulatory nerves can represent the primary pathogenic events. This leads to progressive damage of tissue with extremely poor capacity for self-regeneration. Inflammation, be it primary/autoimmune or secondary/degenerative, leads to peripheral sensitization and stimulation, which may further lead to central sensitization, neurogenic amplification of the inflammatory responses and activation of the neuro-endocrine axis. Neuropeptides serve as messengers, which modulate and mediate the actions in these cascades. Accordingly, many neuropeptides have been used successfully as experimental treatments, most recently VIP, which effectively controlled collagen-induced arthritis in mice. Therefore, it can safely be concluded that better treatment/control of disease activity and pain can be achieved by blocking the cascade leading to initiation and/or amplification of inflammatory process combined with effects on central nociceptive and neuroendocrine responses.
Niissalo
S
S
Biomedicum Helsinki, Institute of Biomedicine/Anatomy, University of Helsinki, Finland.
Hukkanen
M
M
Imai
S
S
Törnwall
J
J
Konttinen
Y T
YT
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000503:physiopathology; D001327:Autoimmune Diseases / Q000503:physiopathology; D000242:Cyclic AMP / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D018846:Excitatory Amino Acids / Q000502:physiology; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D018836:Inflammation Mediators / Q000502:physiology; D008954:Models, Biological; D009410:Nerve Degeneration / Q000150:complications* / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000502:physiology; D015213:Neuroimmunomodulation / Q000502:physiology*; D009473:Neuronal Plasticity; D009475:Neurons, Afferent / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D010003:Osteoarthritis / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D017779:Sympathetic Fibers, Postganglionic / Q000503:physiopathology; D013583:Synovial Membrane / Q000294:innervation
D016207:Cytokines; D018846:Excitatory Amino Acids; D012739:Gonadal Steroid Hormones; D018836:Inflammation Mediators; D009479:Neuropeptides; D020932:Nerve Growth Factor; D000242:Cyclic AMP