en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="background:white"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Neuropathic pain (NP) results from injuries or diseases of the sensory nervous system. Symptoms of this condition include spontaneous pain, hyperalgesia, and allodynia. Due to the complexity of the mechanism, conventional painkillers are ineffective. Recent preclinical research has shown promising results in treating NP with stem cells. </span></span></span></span></span><span dir="RTL" lang="FA" style="font-size:12.0pt"><span style="background:white"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="background:white"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Despite the importance of the beneficial effects of stem cells, there remains a&nbsp;paucity&nbsp;of evidence on optimizing the dose and cell delivery routes of stem cells during NP.&nbsp; To this end, we evaluated two doses and routes of administration of bone marrow mesenchymal stem cells (BM-MSCs) in the chronic constriction injury (CCI)-induced neuropathic pain model. To compare doses and routes of administration (intravenous and intralesional injections), pain sensitization, oxidative stress, and astrogliosis assessments were performed. </span></span></span></span></span><span dir="RTL" lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="background:white"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">We found that a significant reduction in pain sensitization parameters was observed on most experimental days. High-dose treatment (intravenous and intralesional injections) and low dose treatment (intralesional injection) produced an antinociceptive effect. Although the low dose (intravenous injection) decreased pain sensitization parameters, the reduction in neuropathic pain did not reach statistical significance compared to the CCI group. Our data demonstrated that intravenous and intralesional injections of BM-MSCs significantly improved oxidative stress by inhibiting the level of malondialdehyde (MDA) compared to the CCI group. In addition, intravenous and intralesional injections of BM-MSCs decreased astrogliosis in the dorsal horn of the spinal cord, as indicated by GFAP. </span></span></span></span></span><span dir="RTL" lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="background:white"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">In conclusion, BM-MSC transplantation alleviated NP sensitization in the CCI model. </span></span></span></span></span><span style="font-size:12.0pt"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif">These results suggest that optimized dosing and delivery routes of BM-MSCs may represent a promising therapeutic approach for neuropathic pain management.</span></span></span></span></span></span></div> Neuropathic Pain, Neuroinflammation, Bone Marrow Mesenchymal Cells, Oxidative Stress, Cell Therapy, Regenerative Medicine 0 0 http://bcn.iums.ac.ir/browse.php?a_code=A-10-3091-3&slc_lang=en&sid=1 mehrdad hajinejad mehrdadhajinejad@gmail.com 13700319475328460059219 13700319475328460059219 No Qaen Faculty of Medical Sciences, Birjand University of Medical Sciences, Birjand, Iran. Saeideh Nemati nemati.saeideh@gmail.com 13700319475328460059220 13700319475328460059220 No Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran fatemeh forouzanfar forouzanfarff@gmail.com 13700319475328460059221 13700319475328460059221 Yes Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran