Research

17 pages, 5071 KiB

Open AccessArticle

Exploring the Therapeutic Potential of Berberine and Tocopherol in Managing Diabetic Neuropathy: A Comprehensive Approach towards Alleviating Chronic Neuropathic Pain

by Faisal K. Alkholifi, Alhussain H. Aodah, Ahmed I. Foudah and Aftab Alam

Biomedicines 2023, 11(6), 1726; https://doi.org/10.3390/biomedicines11061726 - 15 Jun 2023

Viewed by 2128

Abstract

Diabetic neuropathy (DN) causes sensory dysfunction, such as numbness, tingling, or burning sensations. Traditional medication may not ease pain and discomfort, but natural remedies such as Berberine (BR) and vitamin E or Tocopherol (TOC) have therapeutic potential to reduce inflammation while improving nerve [...] Read more.

Diabetic neuropathy (DN) causes sensory dysfunction, such as numbness, tingling, or burning sensations. Traditional medication may not ease pain and discomfort, but natural remedies such as Berberine (BR) and vitamin E or Tocopherol (TOC) have therapeutic potential to reduce inflammation while improving nerve function. Novel substances offer a more potent alternative method for managing severe chronic neuropathic pain that does not react to standard drug therapy by targeting various pathways that regulate it. Rats with diabetic control received oral doses of BR + TOC that showed significant changes in serum insulin levels compared to DN controls after 90 days, suggesting a decrease in sensitivity to painful stimuli partly by modulating the oxidative stress of the inflammatory pathway such as TNF-α suppression or stimulation of TNF-α depending on the amount of dose consumed by them. NF-kB also played its role here. Administering doses of BR and TOC reduced heightened levels of NF-kB and AGEs, effectively counteracting inflammation-targeted key factors in diabetes, promising possibilities for the benefits of these molecules revealed through in vivo investigation. In summary, treating neuropathy pain with a more comprehensive and organic approach can involve harnessing the powerful capabilities of BR and TOC. These compounds have been found to not only considerably decrease inflammation but also provide effective nerve protection while enhancing overall nerve function. With their multifunctional impacts on various neuropathic pain pathways in the body, these naturally occurring substances offer an exciting possibility for those who encounter high levels of neuropathic distress that do not respond well to conventional medication-centred therapies. Full article

(This article belongs to the Special Issue Neuropathic Pain: Therapy and Mechanisms 2.0)

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12 pages, 1470 KiB

Open AccessArticle

Red Ginger Extract Prevents the Development of Oxaliplatin-Induced Neuropathic Pain by Inhibiting the Spinal Noradrenergic System in Mice

by Keun-Tae Park, Heejoon Jo, Bonglee Kim and Woojin Kim

Biomedicines 2023, 11(2), 432; https://doi.org/10.3390/biomedicines11020432 - 02 Feb 2023

Cited by 2 | Viewed by 1596

Abstract

Oxaliplatin is a well-known chemotherapeutic drug that is widely used to treat colorectal cancer. However, it can induce acute side effects in up to 90% of patients. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are used as first-choice drugs; however, even SNRIs are known [...] Read more.

Oxaliplatin is a well-known chemotherapeutic drug that is widely used to treat colorectal cancer. However, it can induce acute side effects in up to 90% of patients. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are used as first-choice drugs; however, even SNRIs are known to be effective only in treatment and not for prevention. Therefore, finding a drug that can prevent the development of cold and mechanical forms of allodynia induced by oxaliplatin is needed. This study demonstrated that multiple oral administrations of 100 mg/kg and 300 mg/kg of red ginger extract could significantly prevent pain development in mice. The role of the noradrenergic system was investigated as an underlying mechanism of action. Both the spinal α1- and α2-adrenergic receptors were significantly downregulated after treatment. Furthermore, the noradrenaline levels in the serum and spinal cord were upregulated and downregulated after treatment with paclitaxel and red ginger, respectively. As the active sub-component of red ginger, ginsenoside Rg3 (Rg3) was identified and quantified using HPLC. Moreover, multiple intraperitoneal injections of Rg3 prevented the development of pain in paclitaxel-treated mice, suggesting that RG3 may induce the effect of red ginger extract. Full article

(This article belongs to the Special Issue Neuropathic Pain: Therapy and Mechanisms 2.0)

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12 pages, 2663 KiB

Open AccessArticle

Perineural Capsaicin Treatment Inhibits Collateral Sprouting of Intact Cutaneous Nociceptive Afferents

by Péter Sántha, Szandra Lakatos, Ágnes Horváth, Mária Dux and Gábor Jancsó

Biomedicines 2022, 10(6), 1326; https://doi.org/10.3390/biomedicines10061326 - 04 Jun 2022

Viewed by 1490

Abstract

Perineural treatment of peripheral nerves with capsaicin produces a long-lasting selective regional thermo- and chemo-analgesia and elimination of the neurogenic inflammatory response involving degeneration of nociceptive afferent fibers. In this study, we examined longitudinal changes in mustard oil–induced sensory neurogenic vasodilatation and plasma [...] Read more.

Perineural treatment of peripheral nerves with capsaicin produces a long-lasting selective regional thermo- and chemo-analgesia and elimination of the neurogenic inflammatory response involving degeneration of nociceptive afferent fibers. In this study, we examined longitudinal changes in mustard oil–induced sensory neurogenic vasodilatation and plasma extravasation following perineural capsaicin treatment of the rat saphenous nerve utilizing scanning laser Doppler imaging and vascular labeling with colloidal silver. Capsaicin treatment resulted in a marked decrease in mustard oil–induced vasodilatation in the skin area served by the saphenous nerve. Repeated imaging of the vasodilatatory response showed no recovery for at least 7 weeks. However, following transection and ligation of the capsaicin-treated saphenous nerve, a substantial recovery of the vasodilatatory response was observed, suggesting a reinnervation of the chemodenervated skin area by collateral sprouting of neighboring intact sciatic nerve afferents. Elimination of the recovered vascular reaction by capsaicin treatment of the sciatic nerve supported this conclusion. Similar results have been obtained by using the vascular labeling technique. These findings indicate an inhibitory effect of persisting cutaneous nerve fibers on the collateral sprouting of intact nerve fibers into the chemodenervated skin area. These observations may bear implications for the development of sensory disturbances following peripheral nerve injuries. Full article

(This article belongs to the Special Issue Neuropathic Pain: Therapy and Mechanisms 2.0)

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10 pages, 1531 KiB

Open AccessArticle

AI Prediction of Neuropathic Pain after Lumbar Disc Herniation—Machine Learning Reveals Influencing Factors

by André Wirries, Florian Geiger, Ahmed Hammad, Martin Bäumlein, Julia Nadine Schmeller, Ingmar Blümcke and Samir Jabari

Biomedicines 2022, 10(6), 1319; https://doi.org/10.3390/biomedicines10061319 - 04 Jun 2022

Cited by 3 | Viewed by 2204

Abstract

The treatment options for neuropathic pain caused by lumbar disc herniation have been debated controversially in the literature. Whether surgical or conservative therapy makes more sense in individual cases can hardly be answered. We have investigated whether a machine learning-based prediction of outcome, [...] Read more.

The treatment options for neuropathic pain caused by lumbar disc herniation have been debated controversially in the literature. Whether surgical or conservative therapy makes more sense in individual cases can hardly be answered. We have investigated whether a machine learning-based prediction of outcome, regarding neuropathic pain development, after lumbar disc herniation treatment is possible. The extensive datasets of 123 consecutive patients were used to predict the development of neuropathic pain, measured by a visual analogue scale (VAS) for leg pain and the Oswestry Disability Index (ODI), at 6 weeks, 6 months and 1 year after treatment of lumbar disc herniation in a machine learning approach. Using a decision tree regressor algorithm, a prediction quality within the limits of the minimum clinically important difference for the VAS and ODI value could be achieved. An analysis of the influencing factors of the algorithm reveals the important role of psychological factors as well as body weight and age with pre-existing conditions for an accurate prediction of neuropathic pain. The machine learning algorithm developed here can enable an assessment of the course of treatment after lumbar disc herniation. The early, comparative individual prediction of a therapy outcome is important to avoid unnecessary surgical therapies as well as insufficient conservative therapies and prevent the chronification of neuropathic pain. Full article

(This article belongs to the Special Issue Neuropathic Pain: Therapy and Mechanisms 2.0)

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12 pages, 846 KiB

Open AccessArticle

Association of Neuropathic Pain Symptoms with Sensitization Related Symptomatology in Women with Fibromyalgia

by Edurne Úbeda-D’Ocasar, Juan Antonio Valera-Calero, Gracia María Gallego-Sendarrubias, César Fernández-de-las-Peñas, José Luis Arias-Buría, Matilde Morales-Cabezas, Lars Arendt-Nielsen and Margarita Cigarán-Méndez

Biomedicines 2022, 10(3), 612; https://doi.org/10.3390/biomedicines10030612 - 06 Mar 2022

Cited by 8 | Viewed by 2319

Abstract

We aimed to analyze potential correlations between S-LANSS and PainDETECT with proxies for pain sensitization, e.g., the Central Sensitization Inventory (CSI) and pressure pain hyperalgesia (construct validity), pain-related or psychological variables (concurrent validity) in women with fibromyalgia (FMS). One-hundred-and-twenty-six females with FMS completed [...] Read more.

We aimed to analyze potential correlations between S-LANSS and PainDETECT with proxies for pain sensitization, e.g., the Central Sensitization Inventory (CSI) and pressure pain hyperalgesia (construct validity), pain-related or psychological variables (concurrent validity) in women with fibromyalgia (FMS). One-hundred-and-twenty-six females with FMS completed demographic, pain-related variables, psychological, and sensitization outcomes as well as the S-LANSS and the PainDETECT questionnaires. S-LANSS was positively associated with BMI (r = 0.206), pain intensity (r = 0.206 to 0.298) and CSI score (r = 0.336) and negatively associated with all PPTs (r = −0.180 to −0.336). PainDETECT was negatively associated with age (r = −0.272) and all PPTs (r = −0.226 to −0.378) and positively correlated with pain intensity (r = 0.258 to 0.439), CSI (r = 0.538), anxiety (r = 0.246) and depression (r = 0.258). 51.4% of the S-LANSS was explained by PainDETECT (45.3%), posterior iliac PPT (0.2%) and mastoid PPT (5.9%), whereas the 56.4% of PainDETECT was explained by S-LANSS (43.4%), CSI (10.4%), and pain intensity (2.6%). This study found good convergent association between S-LANSS and PainDETECT in women with FMS. Additionally, S-LANSS was associated with PPTs whereas PainDETECT was associated with pain intensity and CSI, suggesting that both questionnaires assess different spectrums of the neuropathic and pain sensitization components of a condition and hence provide synergistic information. Full article

(This article belongs to the Special Issue Neuropathic Pain: Therapy and Mechanisms 2.0)

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Review

Jump to: Research, Other

12 pages, 887 KiB

Open AccessReview

A Literature Review: The Mechanisms and Treatment of Neuropathic Pain—A Brief Discussion

by Renira Rugnath, Casey Orzechowicz, Clayton Newell, Veronica Carullo and Anesh Rugnath

Biomedicines 2024, 12(1), 204; https://doi.org/10.3390/biomedicines12010204 - 17 Jan 2024

Viewed by 1246

Abstract

Classically, neuropathic pain is described as a pain caused by a lesion or disease of the somatosensory system. However, one must note that the presence of somatosensory pathology alone does not guarantee a progression to neuropathic pain. This is due, in part, to [...] Read more.

Classically, neuropathic pain is described as a pain caused by a lesion or disease of the somatosensory system. However, one must note that the presence of somatosensory pathology alone does not guarantee a progression to neuropathic pain. This is due, in part, to the fact that neuropathic pain is a notoriously complex disease process, involving sensitization of both the central and peripheral nervous systems. Its causes are also numerous and varied, including trauma, the compression of a nerve, autoimmune disorders, diabetes, and infections. Due to the various manifestations, causes, and symptoms of neuropathic pain, the treatment of this disease process has proved challenging for generations of physicians. This section aims to elaborate on newly proposed mechanisms for pharmacological and targeted therapies, such as neurostimulation, which aim to reduce the negative somatosensory effects of neuropathic pain. Full article

(This article belongs to the Special Issue Neuropathic Pain: Therapy and Mechanisms 2.0)

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14 pages, 447 KiB

Open AccessReview

Concept of the Number Needed to Treat for the Analysis of Pain Relief Outcomes in Patients Treated with Spinal Cord Stimulation

by Ashley Bailey-Classen, Amar Parikh, Nima Adimi, Deborah Edgar, Alice Yan, Anand Rotte and David Caraway

Biomedicines 2022, 10(2), 497; https://doi.org/10.3390/biomedicines10020497 - 20 Feb 2022

Cited by 3 | Viewed by 2067

Abstract

In the rapidly evolving field of spinal cord stimulation (SCS), measures of treatment effects are needed to help understand the benefits of new therapies. The present article elaborates the number needed to treat (NNT) concept and applies it to the SCS field. We [...] Read more.

In the rapidly evolving field of spinal cord stimulation (SCS), measures of treatment effects are needed to help understand the benefits of new therapies. The present article elaborates the number needed to treat (NNT) concept and applies it to the SCS field. We reviewed the basic theory of the NNT, its calculation method, and its application to historical controlled trials of SCS. We searched the literature for controlled studies with ≥20 implanted SCS patients with chronic axial back and/or leg pain followed for ≥3 months and a reported responder rate defined as ≥50% pain relief. Relevant data necessary to estimate the NNT were extracted from the included articles. In total, 12 of 1616 records were eligible for inclusion. The records reported 10 clinical studies, including 7 randomized controlled trials, 2 randomized crossover trials, and 1 controlled cohort study. The studies investigated traditional SCS and more recently developed SCS modalities, including 10 kHz SCS. In conclusion, the NNT estimate may help SCS stakeholders better understand the effect size difference between compared treatments; however, interpretation of any NNT should take into account its full context. In addition, comparisons across trials of different therapies should be avoided since they are prone to interpretation biases. Full article

(This article belongs to the Special Issue Neuropathic Pain: Therapy and Mechanisms 2.0)

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Other

Jump to: Research, Review

15 pages, 544 KiB

Open AccessSystematic Review

Neuromodulation Therapy for Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review

by Ryan S. D’Souza, Yeng F. Her, Max Y. Jin, Mahmoud Morsi and Alaa Abd-Elsayed

Biomedicines 2022, 10(8), 1909; https://doi.org/10.3390/biomedicines10081909 - 07 Aug 2022

Cited by 13 | Viewed by 2682

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition in patients who have received chemotherapy. The role of neuromodulation therapy in treating pain and improving neurological function in CIPN remains unclear and warrants evidence appraisal. In compliance with the Preferred Reporting Items [...] Read more.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition in patients who have received chemotherapy. The role of neuromodulation therapy in treating pain and improving neurological function in CIPN remains unclear and warrants evidence appraisal. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review to assess change in pain intensity and neurological function after implementation of any neuromodulation intervention for CIPN. Neuromodulation interventions consisted of dorsal column spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), or peripheral nerve stimulation (PNS). In total, 15 studies utilized SCS (16 participants), 7 studies utilized DRG-S (7 participants), and 1 study utilized PNS (50 participants). Per the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria, there was very low-quality GRADE evidence supporting that dorsal column SCS, DRG-S, and PNS are associated with a reduction in pain severity from CIPN. Results on changes in neurological function remained equivocal due to mixed study findings on thermal sensory thresholds and touch sensation or discrimination. Future prospective, well-powered, and comparative studies assessing neuromodulation for CIPN are warranted. Full article

(This article belongs to the Special Issue Neuropathic Pain: Therapy and Mechanisms 2.0)

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