Oligonucleotide IMT504 reduces neuropathic pain after peripheral nerve injury

M.F. CORONEL; A. HERNANDO-INSÚA; J. RODRIGUEZ; F. ELÍAS; J. FLÓ; R. LÓPEZ; N.A. CHASSEING; J. ZORZOPULOS; M.J. VILLAR; A.D. MONTANER

Berlín, Alemania

Congreso; Second International Congress on Neuropathic Pain; 2007

International Association for the Study of Pain

IMT504, the prototype of the PyNTTTTGT class of immunostimulatory oligonucleotides, is a potent stimulatory signal for Mesenchymal Stem Cells (MSC) expansion both in vitro and in vivo. We have also found that exogenous bone marrow-derived MSCs can preferentially migrate to the tissues affected by a peripheral nerve injury and attenuate the neuropathic pain. In this study, we evaluate 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, MSC 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 as compared to controls. Control animals developed both mechanical and thermal allodynia, with lowest paw-withdrawal thresholds at three and seven days post injury. Although the molecular mechanisms involved in the alleviation of pain should be further characterized, preliminary data show that MSCs can attenuate the changes in neuropeptide expression in primary afferent neurons induced by the nerve lesion, thus modifying pain neurotransmission. Numerous studies involving a variety of animal models have shown that MSCs are useful in the repair or regeneration of damaged tissues. However, clearly more important is the rapid pain relieve achieved by systemic treatment with IMT504 by stimulation of MSCs’ own animal, avoiding ex vivo cell manipulation. These results indicate the feasibility of IMT504 as a therapeutic approach for treatment of neuropathic pain.