Oligonucleotide IMT504 reduces neuropathic pain after peripheral nerve injury.
We have recently shown that the administration of bone marrow stromal cells (MSCs) prevents the development of mechanical and thermal allodynia in animals subjected to a sciatic nerve injury. Furthermore, exogenously administered MSCs have been shown to participate in the repair and regeneration of damaged tissues in a variety of animal models. However, some limitations of this therapeutic approach, basically related to the ex vivo cell manipulation procedure, have arisen. IMT504, the prototype of the PyNTTTTGT class of immunostimulatory oligonucleotides, stimulates MSC expansion both in vitro and in vivo. In this study, we evaluated the effect of IMT504 systemic administration on the development of mechanical and thermal allodynia in rats subjected to a sciatic nerve crush. Animals were treated with IMT504, MSCs or saline either immediately after performing the lesion or 4 days after it, and were evaluated using the von Frey and Choi tests at different times after injury. Control animals developed both mechanical and thermal allodynia. Animals receiving either IMT504 or MSCs immediately after injury did not develop mechanical allodynia and presented a significantly lower number of nociceptive responses to cold stimulation as compared to controls. Moreover, injury-induced allodynia was significantly reduced after IMT504 delayed treatment. Our results show that the administration of IMT504 reduces neuropathic pain-associated behaviors, suggesting that IMT504 could represent a possible therapeutic approach for the treatment of neuropathic pain.
Coronel
María Florencia
MF
Facultad de Ciencias Biomédicas, Universidad Austral, Av. Pte. Perón 1500, Buenos Aires B1629AHJ Pilar, Argentina. fcoronel@cas.austral.edu.ar
Hernando-Insúa
Andrés
A
Rodriguez
Juan Manuel
JM
Elias
Fernanda
F
Chasseing
Norma Alejandra
NA
Montaner
Alejandro Daniel
AD
Villar
Marcelo José
MJ
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal; D016026:Bone Marrow Transplantation / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000209:etiology / Q000628:therapy*; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000150:complications; D017154:Stromal Cells / Q000637:transplantation; D013997:Time Factors
D000700:Analgesics; C514285:IMT504; D009838:Oligodeoxyribonucleotides