Paclitaxel (PTX), a commonly used chemotherapeutic, frequently leads to chemotherapy-induced peripheral neuropathy (CIPN), characterized by persistent pain and neuronal hypersensitivity. While its effects on peripheral nerves are well-documented, paclitaxel also influences central nervous system pathways, particularly spinal synaptic transmission, through Toll-like receptor 4 (TLR4) activation and subsequent sensitization of transient receptor potential vanilloid 1 (TRPV1) receptors. In this study, we used an in vitro model of paclitaxel-induced neuropathic pain to investigate the role of glial activation in TRPV1 receptor function. Using whole-cell patch-clamp recordings from superficial dorsal horn neurons in acute spinal cord slices, we evaluated the effects of minocycline (MX), a glial cell inhibitor, and ISO-1, a macrophage migration inhibitory factor (MIF) antagonist, on paclitaxel-induced synaptic changes. Our results demonstrate that acute paclitaxel application enhances nociceptive signaling and impairs capsaicin-induced TRPV1 receptor tachyphylaxis, leading to sustained hyperactivity. Minocycline preincubation effectively mitigated paclitaxel-induced sensitization, restoring normal nociceptive signaling, whereas acute minocycline treatment failed to prevent these changes. ISO-1 in vitro co-incubation with paclitaxel did not affect the paclitaxel-induced changes. These findings offer novel insight into the intricate interactions among neuroinflammatory mediators, glial cell activation, and TRPV1 receptor sensitization in paclitaxel-induced neuropathic pain. The differential effects of acute versus prolonged pre-incubation minocycline application suggest the importance of sustained glial inhibition for effective outcomes and neuropathic pain management.

• MeSH
• fytogenní protinádorové látky toxicita   MeSH
• kationtové kanály TRPV * metabolismus   MeSH
• krysa rodu Rattus MeSH
• mícha * metabolismus   účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• neuralgie * chemicky indukované   metabolismus   MeSH
• neuroglie * metabolismus   účinky léků   MeSH
• paclitaxel * toxicita   MeSH
• potkani Sprague-Dawley MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fytogenní protinádorové látky MeSH
• kationtové kanály TRPV * MeSH
• paclitaxel * MeSH
• Trpv1 protein, rat MeSH Prohlížeč
• TRPV1 receptor MeSH Prohlížeč

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

Postoperative pain is a prevalent problem, often lasting from days to years. To minimize opioid use and associated risks of dependency, Enhanced Recovery After Surgery (ERAS) protocols increasingly incorporate multimodal analgesics. Sodium channel-selective blockers are a promising non-opioid alternative, yet their application in postoperative pain remains underexplored. This systematic review evaluates their efficacy in managing postoperative, neuropathic, and neuralgia-related pain. A systematic review was conducted using controlled keywords across multiple databases to identify studies on sodium channel-selective blockers published up to 2024. Eligible studies included clinical trials, observational studies, case series, and reports involving patients aged 18 or older. Data were extracted on therapeutic outcomes, dosages, complications, and comparisons with other analgesics. Five studies met the inclusion criteria, involving 804 patients, 81.58% of whom were women. One study addressed postoperative pain, while the remaining five focused on neuropathy- and neuralgia-related pain. All studies reported significant pain reduction in at least one treatment group compared with placebo. In the study on postoperative pain, the sodium channel-selective blocker significantly reduced pain scores without requiring opioid analgesia. Across all studies, only two patients needed concomitant opioid therapy, and one discontinued treatment due to adverse effects. Dosages varied, with no reports of severe complications. Comparative analyses showed that sodium channel-selective blockers were as effective, if not superior, to traditional pain medications in reducing pain intensity. Sodium channel-selective blockers demonstrate significant potential in pain management with minimal opioid reliance. While effective for neuropathic pain, further studies are essential to validate their role in acute postoperative settings and refine their use in multimodal analgesia regimens.

• Klíčová slova
• innovation, pain management, sodium channel-selective analgesics,
• MeSH
• analgetika * terapeutické užití   MeSH
• blokátory sodíkových kanálů * terapeutické užití   MeSH
• lidé MeSH
• management bolesti * metody   MeSH
• neuralgie * farmakoterapie   MeSH
• pooperační bolest * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH
• Názvy látek
• analgetika * MeSH
• blokátory sodíkových kanálů * MeSH

Spinal cord injury (SCI) often leads to central neuropathic pain, a condition associated with significant morbidity and is challenging in terms of the clinical management. Despite extensive efforts, identifying effective biomarkers for neuropathic pain remains elusive. Here we propose a novel approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with artificial neural networks (ANNs) to discriminate between mass spectral profiles associated with chronic neuropathic pain induced by SCI in female mice. Functional evaluations revealed persistent chronic neuropathic pain following mild SCI as well as minor locomotor disruptions, confirming the value of collecting serum samples. Mass spectra analysis revealed distinct profiles between chronic SCI and sham controls. On applying ANNs, 100% success was achieved in distinguishing between the two groups through the intensities of m/z peaks. Additionally, the ANNs also successfully discriminated between chronic and acute SCI phases. When reflexive pain response data was integrated with mass spectra, there was no improvement in the classification. These findings offer insights into neuropathic pain pathophysiology and underscore the potential of MALDI-TOF MS coupled with ANNs as a diagnostic tool for chronic neuropathic pain, potentially guiding attempts to discover biomarkers and develop treatments.

• Klíčová slova
• Artificial intelligence, Artificial neural networks, Central neuropathic pain, MALDI-TOF MS, Spectral profiles, mass spectrometry, spinal cord injury,
• MeSH
• biologické markery krev   MeSH
• chronická bolest krev   diagnóza   etiologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neuralgie * krev   diagnóza   etiologie   MeSH
• neuronové sítě * MeSH
• poranění míchy * komplikace   krev   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice * metody   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH

One of the most common issues caused by antineoplastic agents is chemotherapy-induced peripheral neuropathy (CIPN). In patients, CIPN is a sensory neuropathy accompanied by various motor and autonomic changes. With a high prevalence of cancer patients, CIPN is becoming a major problem for both cancer patients and for their health care providers. Nonetheless, there are lacking effective interventions preventing CIPN and treating the CIPN symptoms. A number of studies have demonstrated the cellular and molecular signaling pathways leading to CIPN using experimental models and the beneficial effects of some interventions on the CIPN symptoms related to those potential mechanisms. This review will summarize results obtained from recent human and animal studies, which include the abnormalities in mechanical and temperature sensory responses following chemotherapy such as representative bortezomib, oxaliplatin and paclitaxel. The underlying mechanisms of CIPN at cellular and molecular levels will be also discussed for additional in-depth studies needed to be better explored. Overall, this paper reviews the basic picture of CIPN and the signaling mechanisms of the most common antineoplastic agents in the peripheral and central nerve systems. A better understanding of the risk factors and fundamental mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies.

• MeSH
• lidé MeSH
• nádory farmakoterapie   MeSH
• neuralgie * chemicky indukované   farmakoterapie   MeSH
• protinádorové látky * škodlivé účinky   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protinádorové látky * MeSH

The cellular distribution and changes in CX3CL1/fractalkine and its receptor CX3CR1 protein levels in the trigeminal subnucleus caudalis (TSC) of rats with unilateral infraorbital nerve ligation (IONL) were investigated on postoperation days 1, 3, 7, and 14 (POD1, POD3, POD7, and POD14, respectively) and compared with those of sham-operated and naïve controls. Behavioral tests revealed a significant increase in tactile hypersensitivity bilaterally in the vibrissal pads of both sham- and IONL-operated animals from POD1 to POD7, with a trend towards normalization in sham controls at POD14. Image analysis revealed increased CX3CL1 immunofluorescence (IF) intensities bilaterally in the TSC neurons of both sham- and IONL-operated rats at all survival periods. Reactive astrocytes in the ipsilateral TSC also displayed CX3CL1-IF from POD3 to POD14. At POD1 and POD3, microglial cells showed high levels of CX3CR1-IF, which decreased by POD7 and POD14. Conversely, CX3CR1 was increased in TSC neurons and reactive astrocytes at POD7 and POD14, which coincided with high levels of CX3CL1-IF and ADAM17-IF. This indicates that CX3CL1/CX3CR1 may be involved in reciprocal signaling between TSC neurons and reactive astrocytes. The level of CatS-IF in microglial cells suggests that soluble CX3CL1 may be involved in neuron-microglial cell signaling at POD3 and POD7, while ADAM17 allows this release at all studied time points. These results indicate an extended CX3CL1/CX3CR1 signaling axis and its role in the crosstalk between TSC neurons and glial cells during the development of trigeminal neuropathic pain.

• Klíčová slova
• chemokine receptors, chemokines, image analysis, immunohistochemistry, microglial cells, neurons, reactive astroglia,
• MeSH
• astrocyty metabolismus   MeSH
• chemokin CX3CL1 * metabolismus   MeSH
• CX3C chemokinový receptor 1 * metabolismus   genetika   MeSH
• krysa rodu Rattus MeSH
• mikroglie metabolismus   MeSH
• neuralgie trigeminu metabolismus   patologie   MeSH
• neuralgie metabolismus   patologie   MeSH
• neurony metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chemokin CX3CL1 * MeSH
• CX3C chemokinový receptor 1 * MeSH
• Cx3cl1 protein, rat MeSH Prohlížeč
• CX3CR1 protein, rat MeSH Prohlížeč

OBJECTIVE: To create a comprehensive overview of imaging methods for diagnosing pudendal neuralgia. METHODOLOGY: Literature review. CONCLUSION: Pudendal neuralgia is a chronic pain condition that is difficult to diagnose. On average, it takes 5 years from the onset of symptoms to the correct diagnosis. Diagnosis is based on symptoms described by the patient, neuropelveological physical examination, and presence of the 5 Nantes criteria. Imaging methods, especially ultrasound and magnetic resonance imaging of the pudendal nerve, show great promise for a more accurate and faster diagnosis. These methods can assist in diagnosing issues and excluding other pathologies that may cause symptoms.

• Klíčová slova
• chronic pelvic pain, imaging, imaging methods, magnetic resonance, pudendal nerve, pudendal neuralgia,
• MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• pudendální nerv diagnostické zobrazování   MeSH
• pudendální neuralgie * diagnóza   diagnostické zobrazování   MeSH
• ultrasonografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: The pudendal nerve is an anatomical structure arising from the ventral branches of the spinal roots S2-S4. Its complex course may be affected by surrounding structures. This may result in irritation or entrapment of the nerve with subsequent clinical symptoms. Aim of this study is to review the anatomy of the pudendal nerve and to provide detailed photographic documentation of the areas with most frequent clinical impact which are essential for surgical approach. METHODS: Major medical databases were searched to identify all anatomical studies investigating pudendal nerve and its variability, and possible clinical outcome of these variants. Extracted data consisted of morphometric parameters, arrangement of the pudendal nerve at the level of roots, formation of pudendal nerve, position according to sacrospinal and sacrotuberal ligaments and its terminal branches. One female cadaver hemipelvis was dissected with common variability of separate course of inferior rectal nerve. During dissection photodocumentation was made to record course of pudendal nerve with focus on areas with recorded pathologies and areas exposed to iatrogenic damage during surgical procedures. RESULTS: Narrative review was done to provide background for photodocumentation. Unique photos of course of the pudendal nerve was made in areas with great clinical significance. CONCLUSION: Knowledge of anatomical variations and course of the pudendal nerve is important for examinations and surgical interventions. Surgically exposed areas may become a site for iatrogenic damage of pudendal nerve; therefore, unique picture was made to clarify topographic relations.

• Klíčová slova
• Anatomical variation, Entrapment, Pudendal nerve, Pudendal neuralgia, Sacrospinous ligament, Sacrotuberous ligament,
• MeSH
• disekce MeSH
• iatrogenní nemoci MeSH
• kloubní ligamenta MeSH
• lidé MeSH
• mrtvola MeSH
• pánev MeSH
• pudendální nerv * anatomie a histologie   MeSH
• pudendální neuralgie * chirurgie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Methylphenidate is a psychostimulant that increases dopamine and noradrenaline levels. Recent studies have shown that methylphenidate potentiates the effect of morphine and together suppress acute and chronic pain. In clinical practice, methylphenidate has been used as a treatment for ADHD and changes of pain threshold have been noted in these patients. The aim of this study was to determine the effect of methylphenidate in an animal model of peripheral neuropathic pain. Neuropathic pain was modeled by the chronic constriction of the sciatic nerve (CCI) in Wistar rats. We evaluated the effect of methylphenidate (1 mg/kg, s.c.) on evoked pain (reflex tests - plantar test, vonFrey test and operant test - thermal place preference) and on spontaneous pain (conditioned place preference). CCI induced thermal, mechanical and cold hyperalgesia/allodynia. Methyphenidate suppressed mechanical and cold hyperalgesia/allodynia, while had no effect on thermal one. Therefore, methylphenidate seems to be a new potential pharmacotherapy for the treatment of neuropathic pain.

• MeSH
• hyperalgezie farmakoterapie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• methylfenidát * farmakologie   terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• neuralgie * farmakoterapie   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• methylfenidát * 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