Oligonucleotide IMT504 reduces mechanical and thermal allodynia after sciatic nerve lesion

CORONEL MF; HERNANDO INSÚA A; RODRIGUEZ JM; ELÍAS F; FLO J; LÓPEZ RA; CHASSEING NA; ZORZOPULOS J; MONTANER AD; VILLAR MJ

San Diego

Congreso; Neuroscience 2007; 2007

Society for Neuroscience

IMT504, the prototype of the PyNTTTTGT class of immunostimulatory oligonucleotides, is a potent stimulatory signal for Mesenchymal Stem Cell (MSC) expansion both in vitro and in vivo. We have previously found that exogenous bone marrow-derived MSCs preferentially migrate to the tissues affected by a peripheral nerve injury and attenuate neuropathic pain. In this study, we have evaluated the effect of IMT504 administration on the development of mechanical and thermal allodynia induced by a sciatic nerve crush. Rats were treated either with IMT504, MSCs or saline and evaluated using the von Frey and Choi tests at different times after injury. Animals receiving either IMT504 or MSC treatment did not develop mechanical allodynia and presented a significantly lower number of nociceptive responses to cold stimulation when compared to controls. Control animals developed mechanical allodynia three, seven and ten days post injury, and presented the major number of nociceptive responses to cold stimuli three days after the lesion. Preliminary data show that MSCs attenuate the changes in neuropeptide expression induced by the nerve lesion in primary afferent neurons, thus modifying pain neurotransmission. MSCs have been proposed as a possible therapeutic strategy for tissue repair therapies. The alleviation of pain induced by IMT504 was similar to that achieved after the administration of MSCs. However, systemic treatment with IMT504 has the advantage of avoiding ex vivo cell manipulation. Our results indicate the feasibility of using IMT504 as a therapeutic approach for the treatment of neuropathic pain.