Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice

Abstract

More than half of spinal cord injury (SCI) patients develop central neuropathic pain (CNP), which is largely refractory to current treatments. Considering the preclinical evidence showing that polyphenolic compounds may exert antinociceptive effects, the present work aimed to study preventive effects on SCI-induced CNP development by repeated administration of two vegetal polyphenolic extracts: grape stalk extract (GSE) and coffee extract (CE). Thermal hyperalgesia and mechanical allodynia were evaluated at 7, 14 and 21 days postinjury. Then, gliosis, ERK phosphorylation and the expression of CCL2 and CX3CL1 chemokines and their receptors, CCR2 and CX3CR1, were analyzed in the spinal cord. Gliosis and CX3CL1/CX3CR1 expression were also analyzed in the anterior cingulate cortex (ACC) and periaqueductal gray matter (PAG) since they are supraspinal structures involved in pain perception and modulation. GSE and CE treatments modulated pain behaviors accompanied by reduced gliosis in the spinal cord and both treatments modulated neuron-glia crosstalk-related biomolecules expression. Moreover, both extracts attenuated astrogliosis in the ACC and PAG as well as microgliosis in the ACC with an increased M2 subpopulation of microglial cells in the PAG. Finally, GSE and CE prevented CX3CL1/CX3CR1 upregulation in the PAG, and modulated their expression in ACC. These findings suggest that repeated administrations of either GSE or CE after SCI may be suitable pharmacologic strategies to attenuate SCI-induced CNP development by means of spinal and supraspinal neuroinflammation modulation.