THE PERIPHERAL NERVOUS SYSTEM (PNS) has three primary functions:
1) relaying sensorimotor information to and from the central
nervous system;
2) controlling local blood flow; and
3) influencing
inflammatory, proliferative, and reparative processes in injured
tissue. In the PNS, neurogenic factors, such as neuropeptides
and neurotransmitters, are chemical agents that mediate these
functions (
35). These factors can influence PNS-related actions
by modulating immune cell responses, cytokine response, and
local blood flow (
5,
35). Although neurogenic factors are released
from stimulated nerve endings, their actions are not restricted
to the point of stimulation (
10). For example, the autonomic
neuropeptides vasoactive intestinal peptide (VIP) and neuropeptide
Y (NPY) can have angiogenic, vasoregulatory, and cell proliferative
actions hours to days after release from nerve endings (
35,
44). In addition, Ackermann et al. (
1) recently reported a role
for peripheral neuropeptides in healing of tendon tissue. The
above observations make it likely that these neurogenic factors
play an important role in tissue homeostasis.
Clinically, chemical inhibition of the PNS is used to manage joint pain. Chemical blockade of the sympathetic nervous system is often accomplished through the administration of guanethidine. Guanethidine blocks the release and subsequent reuptake of norepinephrine (NE) (a major sympathetic neurotransmitter) in patients with osteoarthritis, rheumatoid arthritis, and reflex sympathetic dystrophy (12, 13, 24, 38, 40). This treatment, while effective in relieving pain, may have undesirable effects on connective tissues, because it alters the normal concentration of neurogenic factors.
Growing anatomic and physiological evidence suggest that the
PNS is important to ligament and joint homeostasis.
Denervation of peripheral nerves leads to decreased healing of the MCL and promotes the onset of osteoarthritis (
22,
34). Partial injury to the MCL
can lead to increases in vascular volume, a factor that is largely
controlled by ligament innervation (
7). During periods of chronic
overuse or disuse, homeostatic changes can be detrimental to
the structural integrity of ligaments. Although the above evidence
suggests that peripheral nerves play an essential role in ligament
homeostasis, few studies exist that directly investigate this
role.
J Appl Physiol 96: 711-718, 2004