Neuropathic pain after spinal cord injury lacks any effective treatments, often leading to chronic pain. This study tested whether the daily administration of fully characterized polyphenolic extracts from grape stalks and coffee could prevent both reflexive and non-reflexive chronic neuropathic pain in spinal cord-injured mice by modulating the neuroimmune axis. Female CD1 mice underwent mild spinal cord contusion and received intraperitoneal extracts in weeks one, three, and six post-surgery. Reflexive pain responses were assessed weekly for up to 10 weeks, and non-reflexive pain was evaluated at the study's end. Neuroimmune crosstalk was investigated, focusing on glial activation and the expression of CCL2/CCR2 and CX3CL1/CX3CR1 in supraspinal pain-related areas, including the periaqueductal gray, rostral ventromedial medulla, anterior cingulate cortex, and amygdala. Repeated treatments prevented mechanical allodynia and thermal hyperalgesia, and also modulated non-reflexive pain. Moreover, they reduced supraspinal gliosis and regulated CCL2/CCR2 and CX3CL1/CX3CR1 signaling. Overall, the combination of polyphenols in these extracts may offer a promising pharmacological strategy to prevent chronic reflexive and non-reflexive pain responses by modifying central sensitization markers, not only at the contusion site but also in key supraspinal regions implicated in neuropathic pain. Overall, these data highlight the potential of polyphenolic extracts for spinal cord injury-induced chronic neuropathic pain.

• Klíčová slova
• chemokines, chronic neuropathic pain, glia, neuroinflammation, polyphenols, spinal cord injury,
• MeSH
• chemokin CCL2 metabolismus   MeSH
• chemokin CX3CL1 metabolismus   MeSH
• CX3C chemokinový receptor 1 metabolismus   MeSH
• glióza * farmakoterapie   metabolismus   MeSH
• hyperalgezie farmakoterapie   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• neuralgie * farmakoterapie   metabolismus   etiologie   prevence a kontrola   MeSH
• polyfenoly * farmakologie   aplikace a dávkování   MeSH
• poranění míchy * komplikace   farmakoterapie   metabolismus   MeSH
• receptory CCR2 metabolismus   MeSH
• rostlinné extrakty * farmakologie   aplikace a dávkování   MeSH
• signální transdukce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Ccl2 protein, mouse MeSH Prohlížeč
• Ccr2 protein, mouse MeSH Prohlížeč
• chemokin CCL2 MeSH
• chemokin CX3CL1 MeSH
• CX3C chemokinový receptor 1 MeSH
• Cx3cr1 protein, mouse MeSH Prohlížeč
• polyfenoly * MeSH
• receptory CCR2 MeSH
• rostlinné extrakty * MeSH

Pathological pain subtypes can be classified as either neuropathic pain, caused by a somatosensory nervous system lesion or disease, or nociplastic pain, which develops without evidence of somatosensory system damage. Since there is no gold standard for the diagnosis of pathological pain subtypes, the proper classification of individual patients is currently an unmet challenge for clinicians. While the determination of specific biomarkers for each condition by current biochemical techniques is a complex task, the use of multimolecular techniques, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), combined with artificial intelligence allows specific fingerprints for pathological pain-subtypes to be obtained, which may be useful for diagnosis. We analyzed whether the information provided by the mass spectra of serum samples of four experimental models of neuropathic and nociplastic pain combined with their functional pain outcomes could enable pathological pain subtype classification by artificial neural networks. As a result, a simple and innovative clinical decision support method has been developed that combines MALDI-TOF MS serum spectra and pain evaluation with its subsequent data analysis by artificial neural networks and allows the identification and classification of pathological pain subtypes in experimental models with a high level of specificity.

• Klíčová slova
• MALDI-TOF MS, artificial intelligence, diagnostics, fibromyalgia, mass spectrometry, neuropathic pain,
• MeSH
• bolest diagnóza   MeSH
• lidé MeSH
• neuronové sítě * MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice metody   MeSH
• umělá inteligence * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Central neuropathic pain is not only characterized by reflexive pain responses, but also emotional or affective nonreflexive pain responses, especially in women. Some pieces of evidence suggest that the activation of the neuroimmune system may be contributing to the manifestation of mood disorders in patients with chronic pain conditions, but the mechanisms that contribute to the development and chronicity of CNP and its associated disorders remain poorly understood. This study aimed to determine whether neuroinflammatory factor over-expression in the spinal cord and supraspinal structures may be associated with reflexive and nonreflexive pain response development from acute SCI phase to 12 weeks post-injury in female mice. The results show that transient reflexive responses were observed during the SCI acute phase associated with transient cytokine overexpression in the spinal cord. In contrast, increased nonreflexive pain responses were observed in the chronic phase associated with cytokine overexpression in supraspinal structures, especially in mPFC. In addition, results revealed that besides cytokines, the mPFC showed an increased glial activation as well as CX3CL1/CX3CR1 upregulation in the neurons, suggesting the contribution of neuron-glia crosstalk in the development of nonreflexive pain responses in the chronic spinal cord injury phase.

• Klíčová slova
• CX3CL1/CX3CR1, central neuropathic pain, chemokines, chronic pain, cytokines, gliosis, neuroinflammation, spinal cord injury,
• MeSH
• mícha MeSH
• myši MeSH
• neuralgie * komplikace   MeSH
• neuroglie MeSH
• neurozánětlivé nemoci MeSH
• poranění míchy * komplikace   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• 4-O-caffeoylquinic acid, chlorogenic acid, coffee extract, gliosis, neochlorogenic acid, neuropathic pain, polyphenols, spinal cord injury,
• Publikační typ
• časopisecké články MeSH