Central Neuropathic Pain Development Modulation Using Coffee Extract Major Polyphenolic Compounds in Spinal-Cord-Injured Female Mice

SIMPLE SUMMARY: Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system, and it is known to have harmful effects on the quality of life of sufferers. It is characterized by hyperalgesia induced by a stimulus that normally provokes pain and allodynia due to a painless stimulus. Nowadays, no effective treatments are available to relieve neuropathic pain; hence, new pharmacological strategies are needed. Recently, it has been shown that coffee extract may prevent the development of neuropathic pain in mice subjected to spinal cord contusion, but it is unknown whether its effects are associated with the administration of the whole extract, or, in contrast, if its polyphenolic compounds could exert these effects when singly administered. Thus, the three major coffee extract polyphenols were separately administered to spinal-cord-injured mice to evaluate their pain alleviation effects compared with those exerted by whole coffee extract administration. Moreover, the reactivity of spinal cord non-neuronal cells was evaluated to elucidate whether their potential effects were associated with their modulation. The results indicated that although the major polyphenols modulated neuropathic pain development, the administration of the whole extract exerted the most beneficial effects. ABSTRACT: It was recently shown that coffee polyphenolic extract exerts preventive effects on central neuropathic pain development, but it is unknown whether its beneficial effects are associated with only one of its major polyphenolic compounds or if the whole extract is needed to exert such effects. The main objective of this study was to determine whether the separate administration of major polyphenols from coffee extract exerts preventive effects on the development of central neuropathic pain in mice compared with the effects of the whole coffee extract. Thus, spinal-cord-injured female ICR-CD1 mice were daily treated with either coffee extract or its major polyphenolic compounds during the first week, and reflexive and nonreflexive pain responses were evaluated within the acute phase of spinal cord injury. In addition, the injury-induced gliosis and dorsal horn sprouting were evaluated with immunohistochemistry. The results showed that the coffee extract prevented spinal cord injury-induced neuropathic pain, whereas its major polyphenolic compounds resulted in reflexive pain response attenuation. Both preventive and attenuation effects were associated with gliosis and afferent fiber sprouting modulation. Overall, the results suggested that coffee extract effects may be associated with potential synergistic mechanisms exerted by its major polyphenolic compounds and not by the sole effect of only one of them.