Tendon Innervation and Neuronal Response After Injury

Abstract

The mediators of the nervous system act through 2 principally different ways: 1) With fast transmitters, i.e. classical neurotransmitters (monoamines, acetylcholine, amino acids), which directly effectuate muscle contractions or afferently relay information on painful stimuli. 2) With a family of slow transmitters, neuropeptides, which slowly regulate physiological functions in the central as well as peripheral nervous system. Neuropeptides Neuropeptides act as chemical messengers and regulators in the central and peripheral nervous systems. They differ from classical neurotransmitters in several respects. Peripheral neuropeptides are synthesized in the cell bodies, i.e. the dorsal root ganglia (sensory) and the sympathetic chain (autonomic), and transported distally. In contrast, classical neurotransmitters are synthesized in the axon terminals, thus exerting their effects more locally. Synthesis and turnover of classical transmitters are more rapid than those of neuropeptides leading to more long-lasting regulatory effects of the neuropeptides. Moreover, several neuropeptides are coreleased, also together with classical transmitters [34], which offers the opportunity of a variety of functional interactions. The effects of neuropeptides and classical transmitters are elicited by different mechanisms, resulting in direct effects of classical transmitters, while neuropeptides act in a regulatory, "supervising" fashion. Several neuropeptides have been identified in both the central and peripheral nervous system. So far, however, research on the occurrence and functions of neuro-peptides in tendons has been very limited. Those hypothetically are important for nociception and tissue homeostasis in tendon can be classified in 3 groups; sensory, opioid and autonomic, according to their function and original nerve fiber type finding. Sensory Neuropeptides Sensory primary afferents, C-and Ad-fibers contain substance P (SP) claimed to transmit nociceptive signals [35,40,65]. Calcitonin gene-related peptide (CGRP) co-exists with and potentiates the effect of SP [56,74,77]. Both SP and CGRP have also been shown to exert pro-inflammatory effects such as vasodilation and protein extravasation [13,47,53]. In the periphery, release of SP leads to sensitization of surrounding primary afferents by enhancing cellular release of prostaglandins, histamines and cytokines [63,72]. Recently, however, SP also directly stimulates nociceptor endings [71]. CGRP, often colocal-ized with SP in unmyelinated C fibers, facilitates the 288 P.W. Ackermann et al. release of SP and delays SP degradation in the spinal cord, thereby potentiating the nociceptive effect [38,62,77]. Sensory nerve fibers, interestingly, also seem to contain peptides with anti-nociceptive and anti-inflammatory effects counteracting the effects of SP and CGRP. Thus, galanin (GAL), somatostatin (SOM) as well as opioids, all of which occurring in primary afferents, inhibit inflammation and nociception [17,20,28,68,78]. These anti-nociceptive peptides probably exert their modulatory effect through inhibition of SP release [15,25,78,79].