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BMP-7 protects male and female rodents against neuropathic pain induced by nerve injury through a mechanism mediated by endogenous opioids

Abstract: Neuropathic pain is highly prevalent in pathological conditions such as diabetes, herpes zoster, trauma, etc. The severity and refractoriness to treatments make neuropathic pain a significant health concern. The transforming growth factor (TGF-?) family of cytokines is involved in pain modulation. Bone morphogenetic proteins (BMPs) constitute the largest subgroup within the TGF-? family. BMP-7 induces the transcription of genes coding endogenous opioid precursors in vitro. However, a nociception modulatory function for this cytokine remains unexplored in vivo. Herein, we show that BMP-7 and its type I receptors were detected in regions of the nervous system involved in pain transmission, processing, and modulation. BMP-7 haploinsufficiency confers to male and female mice a tactile hyperalgesia phenotype to mechanical stimuli, both at baseline and after sciatic nerve injury (SNI). The administration of recombinant BMP-7 (rBMP-7) reduced the severity of the allodynia after SNI in rodents without sexual dimorphism. Central administration of rBMP-7 delayed allodynia development after SNI and reduced the severity of allodynia. The opioid antagonist naloxone antagonized the antinociceptive effect of rBMP-7 in rats. The analgesic effect of morphine was significantly attenuated in BMP-7+/- mice. The antiallodynic effect of voluntary exercise after SNI, whose mechanism involves the endogenous opioid system, was hampered by BMP-7 deficiency while potentiated by rBMP-7. Our results suggest that BMP-7 may constitute a novel therapeutic target for the treatment of neuropathic pain, which improves the function of the endogenous pain-resolution mechanisms to alleviate chronic pain.

 Fuente: Pharmacological Research 2019, 150, 104470

 Editorial: Elsevier

 Fecha de publicación: 01/12/2019

 Nº de páginas: 11

 Tipo de publicación: Artículo de Revista

 DOI: 10.1016/j.phrs.2019.104470

 ISSN: 1043-6618,1096-1186

 Proyecto español: SAF2013-47434-R

 Url de la publicación: https://doi.org/10.1016/j.phrs.2019.104470