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

[Display omitted] 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-β) family of cytokines is involved in...

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Bibliographic Details
Published in:Pharmacological research 2019-12, Vol.150, p.104470-104470, Article 104470
Main Authors: de la Puerta, Rosmarí, Carcelén, María, Francés, Raquel, de la Fuente, Roberto, Hurlé, María A., Tramullas, Mónica
Format: Article
Language:English
Subjects:
BMP-7
Endogenous opioids
Exercise
Female
Male
Morphine
Naloxone
Neuropathic pain
TGF-β family
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Summary:[Display omitted] 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-β) family of cytokines is involved in pain modulation. Bone morphogenetic proteins (BMPs) constitute the largest subgroup within the TGF-β 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.
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2019.104470