Contribution of sensory afferents and sympathetic efferents to joint injury in experimental arthritis

Abstract

We used pharmacological and surgical methods to determine the contribution of several neural components to joint injury in rats with adjuvant-induced arthritis. Both neonatal administration of capsaicin, which eliminates small-diameter afferents, and peripheral sympathectomy, which depletes catecholamines, attenuated joint injury. In contrast, the arthritis was more severe in spontaneously hypertensive rats, which have increased sympathetic tone. To address the contribution of the central vs peripheral afferent terminal selectively, a group of rats underwent unilateral dorsal rhizotomy. These rats developed a more severe arthritis in the deafferented limb. The increase in arthritis severity produced by dorsal rhizotomy could be reduced by prior sympathectomy or, less effectively, by prior treatment with capsaicin. The latter observation suggests that large-diameter afferents that are cut during dorsal rhizotomy also influence inflammation. Finally, intracerebroventricular injection of morphine attenuated the severity of arthritis, possibly through activation of bulbospinal sympathoinhibitory circuits. Taken together, these data indicate that no one class of nerve fiber is wholly responsible for the neurogenic component of inflammation in experimental arthritis but that large- and small-diameter afferents, sympathetic efferents, and CNS circuits that modulate those fiber systems all influence the severity of joint injury in arthritic rats.

Sympathetic modulation of immunity: Relevance to disease

“…However, denervation studies in animal models for RA report mixed results depending on whether sympathetic denervation is local or systemic. Systemic depletion of NE using guanethidine, reserpine, or 6-OHDA treatment in rodent models of RA attenuates inflammation and joint destruction [357][358][359][360][361][362]. Additionally, administration of propranolol, a β-AR antagonist, or regional sympathetic blockade with guanethidine reduces symptoms associated with RA in clinical studies [359].…”

Catechol- O -methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors

“…NIH-PA Author Manuscript NIH-PA Author Manuscript arthritis in animals, as denervation of sympathetic noradrenergic fibers (Levine et al 1986a) and depletion of peripheral epinephrine (Coderre et al 1990) attenuate arthritic responses. Additionally, chronic administration of β-adrenergic receptor (βAR) agonists produces a painful arthritis-like syndrome (Vyden et al 1971).…”

Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

“…Neuropeptides have the potential to contribute to inflammatory disease as the "neurogenic component" via a variety of mechanisms (10). Levels of neuropeptides have been shown to be increased in samples of synovial fluid from patients with rheumatoid arthritis (11), and the ligation of sensory nerves in experimental joint inflammation is associated with a beneficial effect (12), providing evidence for involvement of sensory nerve activation in arthritis. Indeed, continued topical treatment with capsaicin has been shown to be beneficial in patients with hand osteoarthritis (13), and capsaicin creams are marketed for the alleviation of pain in diseases including both osteoarthritis and rheumatoid arthritis (14).…”