Neuropathic pain is a chronic condition that is heterogeneous in nature and has different causes. Different from and more burdensome than nociceptive pain, neuropathic pain more severely affects people’s quality of life. Understanding the various mechanisms of the onset and progression of neuropathic pain is important in the development of an effective treatment. Research is being done to replace current pharmacological treatments with cellular therapies that will have longer lasting effects. Stem cells present an exciting potential therapy for neuropathic pain. In this review, we describe the neuroprotective effects of stem cells along with special emphasis on the current translational research using stem cells to treat neuropathic pain.

Keywords: Adult stem cells, Cellular therapy, Neuropathy, Stem cell-microenvironment interactions
In 2008, the International Association for the Study of Pain formed a special interest group to redefine neuropathic pain as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system” []. Neuropathy is heterogeneous in nature; however, neuropathic lesions may be characterized into four broad categories: focal or multifocal lesions of the peripheral nervous system, generalized lesions of the peripheral nervous system (polyneuropathies), lesions of the central nervous system, and complex neuropathic disorders (Table 1) [].

Although categorized as chronic pain, neuropathic pain is regarded as more severe than other types of chronic pain. This is due to the increased disruption of both physical and mental quality of life when compared with other chronic pain syndromes. People with chronic neuropathic pain report a higher severity of pain and significantly worse scores for all interference items of the Brief Pain Inventory than non-neuropathic chronic pain patients. Also, those with chronic neuropathic pain report mean scores for the Neuropathic Pain Scale significantly higher than those with non-neuropathic chronic pain, even after adjusting for pain severity, age, and sex [].

Types of Pain

Neuropathic pain presents itself in many different forms. Spontaneous sensations include paroxysmal pain (shooting pain that lasts several seconds) and superficial pain (an ongoing, burning sensation). Evoked pain includes mechanical allodynia (pain caused by normally nonpainful pressure), heat or cold allodynia (pain caused by normally nonpainful hot/cold stimuli), hyperalgesia (increased sensitivity to a normally painful stimulus), and temporal summation (increasing pain sensation from repetitive application of identical stimuli) [].

Neuropathic pain differs from nociceptive pain in that nociceptive pain is caused by tissue damage, whereas neuropathic pain is produced by nerve damage. In particular, pain signaling areas of the peripheral or central nervous system are injured, causing neuropathic pain. In nociceptive pain, tissue damage causes the generation of prostaglandins that cause vasodilation, increased blood flow, inflammatory exudates, and the sensitization of nociceptive nerve endings. In neuropathic pain, signals are generated by the injured nerve, sent to the brain, and interpreted as pain. Nociceptive pain is proportional to the intensity of the stimulus; neuropathic pain is not—a small stimulus may provoke increased sensations of pain [].

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