الفهرس 
ACKNOWLEDGEMENTOnly 14 pages are availabe for public view
 |  | from | 83 |  |  |
| | | from | 83 | | |
Abstract
The main finding of this study is that intravenous injection of mesenchymalstem cells either after or pre-emptive to surgical induction of neuropathic pain in classical sciatic nerve ligation model is effective. In this study for the first time that single intravenous injection of MSCs in a dose of (1 X 106 ) cell/ml into rat tail vein before (pre-imptive) induction of neuropathic pain act in the same maneuver as post-injury injection in resolving neuropathic pain behaviors without significant difference between two modes of administration of injection. This raises another possibility of mode of action of MSCs and open new possibility of clinical use of MSCs administration before appearance of full signs of neuropathic pain. Early cell therapy might decrease proliferation or hypertrophy of glial cells (gliosis), enhance recovery by bioactive molecules, modulation of cytokines and production and growth factors. consequently, the onset stem cell during the first days after injury (less than 4 days) cause more improvement in allodynia and hyperalgesia , it seems natural to suggest that optimal time of point is few than 4 days. The different modes of administration of stem cell were recorded in experimental models of neuropathic pain. Neuropathic pain is currently defined as a direct consequence of a lesion or disease affecting somatosensory system. it represent a big challenge in both clinical management affecting 1% of the population and pharmacological therapy mainly anticonvulsants and antidepressants with limited success only 30% over placebo. In 1988 Benett and zie introduced in rats as experimental model in which loose constrictive ligatures around the common sciatic nerve inducing post operative behavior of hyperalgesia and allodynia . Hyperalgesia responses to noxious heat were evident on the second post operative day and lasted over 2 months and allodyniawas induced by rat persistence in holding the hind paw in guard position on innocuous chilled metal floor by innocuous stimulation. This animal model closely mimics behavioral signs of clinical neuropathic pain . Sciatic nerve lesion has been reported in 4 groups of rat models where stem cells were given intravenously. Two studies of them used bone marrow mononuclear cells (Klass 2007 and Goe 2009) easily obtained easily differentiated into neural cells. And the other two injected in a rat experimental model of neuropathic pain with either human adipose derived stem cells (sacerdoteetal,2012) or human mesenchymal stem cells. both choose theses cells for immune property and high genetic stability. The main question of this study is to test the ability of rat mesenchymal stem cells to attenuate neuropathic pain behavior in rat models of neuropathic pain when injected intravenously before and after sciatic nerve ligation and whether pre-emptive stem cell injection can make resolve over pain behavior like post injury. The mainfindings of this study is pre-emptive systemic administration of stem cells produce profound effect as effective as post injury. This finding is new and demonstrate the intravenous injection of stem cells can produce pre-injury effect which open concern about how stem cell circulating in systemic administration reach the site of injury. There is a potential of stem cell injected to circulate up to 10 days as recorded in this study. In two published studies intravenous administration of stem cells produce a long term inhibition of neuropathic pain through by stander effect as neuropathic injury activate the immune system and activate glial cells initiating neuro-inflammatory cascade that facilitate pain signaling. The effect of stem cells mostly appears 4-6 days post injury and can last for several days. Our study tested the concept of pre-emptive effect of intravenous stem cells that proved to be equal or even potent than post injury. Early stem cell therapy even before neuropathic behaviors might decrease gliosis and enhance recovery by bioactive molecules, modulation of cytokines production and growth factors producing micro environmental neuroprotective effects. Providing a drug stores using pre-emptive injection of stem cells completely inhibited allodyina and hyperalgesia in this model of neuropathic pain. This open a new window for administration of stem cells on early signs of neuropathy. Neuro-inflammation is a component of neuropathic pain and cytokines that have secretory potential especially in the lack of MSCs localization raised the great possibility that injected stem cells that act either local or distant cytokines actionseems to act a cellular factors even for regeneration and this can explain the mechanism of pre-emptive action of stem cell shown in this study. Pre-emptive Effect: The concept of pre-emptive analgesia includes the administration of analgesic agents before surgical tissue injury. Central and peripheral sensitization are considered the two main plans of pain after injury. It depends on prevention of inflammation thus avoid central sensitization that lead to lowering pain threshold. Stem cell transplantation intrathecally produce anti-hyperalgesic and anti-allodynic effect via release of major anti inflammatory cytokines , TNF that inhibit gliosis. Limitaion of this study: Two points of concern would be further investigated. Tissue examination from the spinal cord and brain to determine the most affected site by MSCs. The second is determination of cytokine milieu following injection of MSCs by the two methods.