**7. Conclusions**

absorbable nerve conduits coated with iPS cell-derived neurospheres were able to repair

86 Peripheral Neuropathy - A New Insight into the Mechanism, Evaluation and Management of a Complex Disorder

Achieving peripheral nerve regeneration, axonal regeneration and re-myelination with stem cells is a challenging research goal. This process is very complex, with Wallerian degeneration being the most elementary reaction and Schwann cells playing an important role. An emerging solution to improve upon this intrinsic regenerative capacity is to supplement injured nerves with stem cells [136]. Stem cells effectiveness in the treatment of peripheral nerve injury may lie in their ability to differentiate into Schwann cells, secrete neurotrophic factors, and assist in myelin formation [137, 136]. This strategy of introduction autologous stem cells directly into the site of a nerve injury represents a promising therapy. Skin-derived precursor cells (SKPs) were successfully transplanted in the sciatic nerve of Lewis rats bridged by a freeze-thawed

The cells were able to improve nerve re-generation, probably their effect was due to the ability to secrete bioactive neurotrophins [138]. Another stem cell type, the multipotent hair follicle stem cells, could provide a potential accessible, autologous source of stem cells for regeneration therapy of damaged nerves [139]. More recently, in an interesting study, Amoh et al. trans‐ planted hair follicle stem cells around the impinged sciatic nerve of the mice. The cells differentiated into glia fibrillary acidic protein-positive Schwann cells, promoting the recovery of pre-existing axons. Authors reported that the regenerated sciatic nerve was functionally recovered [140]. These hair follicle stem cells could differentiate into several cell types, i.e. neurons, glia, keratinocytes, smooth muscle cells and melanocytes. They are nestin-positive cells and once implanted into the gap region of the sciatic or tibial nerve, are able to enhance the rate of nerve regeneration and the restoration of nerve function [141]. Wharton's jelly fishderived mesenchymal stem cells (WJMSCs) could be also a promising cell source for nerve tissue engineering. It has been demonstrated that these cells can be differentiated into Schwann-like cells and could be suitable Schwann-cell substitutes for nerve repair in clinical applications [142]. A recent strategy for peripheral nerve regeneration is based on the use of CD34(+) cells. Indeed, integration of CD34(+) cells in injured nerve significantly promotes nerve regeneration [143]. However, limited migration and short survival of CD34(+) cells could counteract this beneficial effect. One strategy could be the potentiation of CD34(+) cell recruitment triggered by stromal cell-derived factor-1α (SDF-1α) [143]. This strategy based on the over-expression of SDF-1α is providing interesting results in the peripheral neuropathy treatment. It has been proposed that the expression of SDF-1α in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. Intravenous administration of human amniotic fluid-derived mesenchymal stem cells facilitated neural regeneration in a sciatic nerve crush injury model, when recruited by expression of SDF-1α in muscle and nerve after nerve crush injury [144]. As mesenchymal stem cells, amniotic fluidderived mesenchymal stem cells have the ability to secrete neurotrophic factors that are able to promote neuron survival. Their transplantation was able to regenerate the sciatic nerve after crush injury by secretion of neurotrophic factors [145]. Interestingly, the stem cell mediated effects could be enhanced by co-administration of several anti-inflammatory and anti-

peripheral nerve gaps in mice [135].

nerve graft.

Neuropathic pain involves a complex network of mechanisms involving peripheral and central nervous system. The peripheral nerve injury produces abnormal peripheral afferent inputs at the spinal dorsal horn which leads to development of central sensitization and plastic changes in supraspinal areas. The precise contribute of the different brain sites in neuropathic pain development and maintenance is still far to be established. In particular the contribute of the descending pain modulatory system including the PAG and the RVM is dual varying from inhibitory to facilitatory. By this subject strategies able to shift the balance between facilitatory versus inhibitory influences of the descending pathway may be useful to counteract neuro‐ pathic pain symptoms. Cannabinoids have been proved to stimulate the PAG-RVM inhibitory pain control and inhibit neuropathic pain-related allodynia and hyperalgesia.

Neurons are not the only cell type involved in plastic changes at the base of pain hypersensi‐ tivity and activated microglia actively contribute to pain facilitation through a tight interaction with neuron activity and the release of pain mediators. Novel strategies based on switching off the microglia activation represents a possible therapeutic intervention to alleviate neuro‐ pathic pain.

Human mesenchymal stem cell transplantation has shown to reduce astrocytic and microglial cell activation, mechanical allodynia and cellular and molecular pain mechanisms. The therapeutic potentiality of stem cell to alleviate neuropathic pain appears encouraging, however, its clinical application in peripheral neuropathy requires and deserves further investigations.

### **Author details**

Sabatino Maione, Enza Palazzo, Francesca Guida, Livio Luongo, Dario Siniscalco, Ida Marabese, Francesco Rossi and Vito de Novellis

Department of Experimental Medicine, Division of Pharmacology, Second University of Naples, Naples, Italy

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Naples, Naples, Italy

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**Section 2**

**Evaluation and Management of Peripheral**

**Neuropathy**

**Evaluation and Management of Peripheral Neuropathy**

**Chapter 4**

**Compression Neuropathies**

Additional information is available at the end of the chapter

functions lost as a result of denervation are never fully restored.

Upper extremity compression neuropathies are among the most common disorders in plastic surgery, especially in patients with predisposing occupations or with certain medical disor‐ ders. In the past two decades a notable increase in the incidence of this entity has occurred. Therefore, it is mandatory to achieve a prompt diagnosis because they can produce important motor and sensory deficiencies that need to be treated before the development of complica‐ tions, since, despite the capacity for regeneration bestowed on the peripheral nervous system,

There are many different situations that may be a direct cause of nerve compression. Ana‐ tomically, nerves can be compressed when traversing fibro-osseous tunnels, passing between muscle layers, through traction as they cross joints or buckling during certain movements of the wrist and elbow. Other causes include trauma, direct pressure and space-occupying lesions

There are other situations that are not a direct cause of nerve compression, but may increase the risk and may predispose the nerve to be compressed specially when the soft tissues are

Physicians in touch with patients who suffer from upper extremity compression neuropa‐ thies must apply all of their skills to correctly distinguish symptomatic nerve entrapment form other neurologic entities such as myelopathy, braquial plexopathy, radiculopathy, and other central nervous system disorders, that can mimic peripheral nerve entrapment.

and reproduction in any medium, provided the original work is properly cited.

© 2013 Mendoza and Salgado; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

swollen like synovitis, pregnancy, hypothyroidism, diabetes or alcoholism [1].

Javier López Mendoza and Alexandro Aguilera Salgado

http://dx.doi.org/10.5772/55316

**1. Introduction**

**2. Etiology**

at any level in the upper extremity.

**Chapter 4**
