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There are various mechanisms behind the effects in tissues treated with
shock waves. It has been reported that angiogenesis is induced by increased
levels of vascular endothelial growth factor-A, which in turn is triggered by
upregulated activities of nitric oxide synthase (NOS), and extracellular
signal-regulated kinase. On the other hand, enhanced NOS activity also
appears to be responsible for the activation of hypoxia-inducible factor-1
in a variety of cells, depending on the target of ESWT. Low-energy shock
wave treatment has likewise proved to be effective in downregulating
immune responses in acute wounds. ESWT has been reported to reduce
the invasion of macrophages and polymorphonuclear leucocytes into the
wound area, together with the suppressed production of proinflammatory
cytokines and chemokines at the wound matrix ( Davis et al., 2009; Kuo
et al., 2009 ). Similar to its role in inducing angiogenesis in shock wave-
treated tissues, the regulatory function of NOS has been suggested in the
downregulation of inflammatory events in these conditions ( Fig. 3.1 ;
Mariotto et al., 2009 ). Others have described the increased release of fibro-
blast growth factor-2, acting on osteoblasts ( Hausdorf et al., 2011 ), while
osteocalcin, a major bone protein playing an important role in bone miner-
alization, is reportedly upregulated in regenerating the bone after ESWT
( Martini et al., 2003 ). In contrast with these molecules, the role of trans-
forming growth factor-beta remains controversial ( Hausdorf et al., 2011;
Martini et al., 2003 ).
It has been suggested that mesenchymal stem cells may differentiate
toward tissue-specific progenitor cells such as osteoblasts in response to
ESWT ( Chen et al., 2004 ), and the moderate recruitment of endothelial
progenitor cells has been described ( Tinazzi et al., 2011 ). However, the
extent to which these mechanisms are able to contribute to the tissue repair
following ESWT is not clear at present.
4. EFFECTS OF ESWT ON PERIPHERAL NERVES
4.1. Effects of ESWT on sensory nerves
Shock waves have been used extensively to study their effects on sensory
nerves and nerve endings. Application of 1000 impulses of shock waves
(0.08 mJ/mm, 2.4 Hz) resulted in the degeneration of sensory nerve fibers
and endings followed by reinnervation of the affected skin areas ( Ohtori
et al., 2001 ). These changes were accompanied by the reversible and rapid
loss of the immunohistochemical markers protein gene product 9.5 and
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