Localized peripheral neuropathic pain: topical treatment with lidocaine 700 mg medicated plaster in routine clinical practice

Aim: To provide real-world evidence for the effectiveness and tolerability of lidocaine 700 mg medicated plaster (LMP) in localized peripheral neuropathic pain (l-PNP) treatment compared with first-line oral medications (OM). Patients & methods: This was a noninterventional, retrospective 6-month cohort study in patients refractory to at least one recommended OM, using anonymized medical care data from the German Pain eRegistry. Treatment groups were matched by propensity scoring, considering seven predefined confounding factors. The primary effectiveness end point was the absolute change in average pain intensity index from baseline at weeks 4, 12 and 24 of treatment and over the treatment period. Results: A total of 3081 datasets were retained per treatment group. LMP provided superior pain reductions and significantly greater improvements in pain-related impairments of daily living and quality of life with significantly better tolerability (p < 0.001 for all parameters) than OM. Conclusion: These real-world data confirm the effectiveness and good tolerability of LMP for l-PNP treatment under routine medical care.

Scyphocephalione a Isolated from the Stem Bark of Scyphocephalium Ochocoa (Myristicaceae) Attenuate Acute and Chronic Pains Through the Antiinflammatory Activity

Abstract In the treatment of cancer, patients that receive anti-cancer drugs such as Vincristine develop peripheral neuropathic pain. Scyphocephalione A is a new bioactive compound isolated from Scyphocephalium ochocoa (Myristicaceae), a medicinal plant traditionally used in African countries. Recently, an in vitro study has shown its anti-inflammatory and cytotoxic activities on MCF-7 cell line of mammary carcinoma. The purpose of the present study was to assess the in vitro anti-inflammatory and in vivo anti-nociceptive activities of Scyphocephalione A. In vitro tests were carried out on cyclooxygenase and 5-lipoxygenase activities, and on protein denaturation; while in vivo tests were performed on acute and chronic pain models. It was noticed that, Scyphocephalione A (1000 µg/ml), inhibits proteins denaturation, cyclooxygenase and 5-lipoxygenase activities respectively by 74.21%, 75.80% and 64.43%. The dose 50 mg/kg of Scyphocephalione A, inhibits acetic acid (63.43%, p<0.001) and formalin (42.12% (p<0.001) within first phase and 67.53% (p<0.001) within second phase)-induced pains. At the same dose, Scyphocephalione A significantly inhibited mechanical and heat hyperalgesia, as well as cold allodynia induced by vincristine. In addition, the compound restored haematological, biochemical and oxidative stress parameters which were altered following Vincristine administration. These results suggest that Scyphocephalione A is endowed with anti-inflammatory potential and antinociceptive properties. Therefore, Scyphocephalione A can be classified as a promising molecule for the management of peripheral neuropathic pain triggered by anti-cancer drug.

Mirogabalin as a Novel Gabapentinoid for the Treatment of Chronic Pain Conditions: An Analysis of Current Evidence

: Neuropathic pain has presented a challenge for physicians to treat and often requires a multimodal approach with both pharmacologic and lifestyle interventions. Mirogabalin, a potent, selective ligand of the α2δ-1 and α2δ-2 subunits of voltage-gated calcium channels (VGCCs), provides analgesia by inhibiting neurotransmitter release at the presynaptic end of the neuron. Mirogabalin offers more sustained analgesia than its gabapentinoid counterparts in addition to a wider safety margin for adverse events. Recent clinical trials of mirogabalin have demonstrated both efficacy and tolerability of the drug for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia, leading to its approval in Japan. While still not yet FDA approved, mirogabalin is still in its infancy and offers potential into the treatment of neuropathic pain and its associated comorbidities.

Mechanisms Underlying Gastrodin Alleviating Vincristine-Induced Peripheral Neuropathic Pain

Gastrodin (GAS) is the main bioactive ingredient of Gastrodia, a famous Chinese herbal medicine widely used as an analgesic, but the underlying analgesic mechanism is still unclear. In this study, we first observed the effects of GAS on the vincristine-induced peripheral neuropathic pain by alleviating the mechanical and thermal hyperalgesia. Further studies showed that GAS could inhibit the current density of NaV1.7 and NaV1.8 channels and accelerate the inactivation process of NaV1.7 and NaV1.8 channel, thereby inhibiting the hyperexcitability of neurons. Additionally, GAS could significantly reduce the over-expression of NaV1.7 and NaV1.8 on DRG neurons from vincristine-treated rats according to the analysis of Western blot and immunofluorescence results. Moreover, based on the molecular docking and molecular dynamic simulation, the binding free energies of the constructed systems were calculated, and the binding sites of GAS on the sodium channels (NaV1.7 and NaV1.8) were preliminarily determined. This study has shown that modulation of NaV1.7 and NaV1.8 sodium channels by GAS contributing to the alleviation of vincristine-induced peripheral neuropathic pain, thus expanding the understanding of complex action of GAS as a neuromodulator.

A Comprehensive in silico study for the Identification of Therapeutic target against Peripheral Neuropathic Pain in human

Background: VGF (non-acronymic) is a neuropeptide precursor or neuro-protein or neurosecretory protein which plays vital roles in the regulation of gastric contractility, mood regulation, and peripheral neuropathic pain and possibly, cancer. Objective: VGF may be a potential target as it has a unique contribution to the development of neuropathic pain which is a target for Oxymatrine (OMTR). Method: Based on this, we have endeavored to discover VGF inhibitors from the ChEMBL database of Oxymatrine (OMTR) analogues by employing homology modelling, molecular docking and pharmacophore analysis. Result: Our in silico investigation reveals that 13-Methoxymatrine has desired characteristics for becoming a future formulation. Conclusion: To confirm the efficacy of this compound, essential animal and clinical trials are needed to be performed. We believe that our present study will help to find an efficient and effective therapy for treating neuropathic pain in human which is modulated by VGF.

Treatment of neurological complications in patients with type 2 diabetes mellitus at the stage of rehabilitation after COVID-19

Although the predominant clinical manifestation of COVID-19 is a respiratory disease, various neurological symptoms are increasingly being diagnosed, in particular, diabetic polyneuropathy is diagnosed in most patients with diabetes, affecting large and small nerve fibers. Drugs that are traditionally used for neuropathic pain (tricyclic antidepressants, gabapentinoids, etc.), despite their positive effect in eliminating the symptoms of polyneuropathy, often cause side effects and do not impact nerve regeneration. Over the last decade, a group of nucleotides has been used quite actively. Additional information on the effects of this group of drugs was accumulated and there is a gradual transformation, including their compositions. Thus, recently the attention of researchers has been devoted to the study of the effectiveness of the combination of uridine, choline, vitamins B1, B6, B12, and folic acid, which is characterized by a fairly high safety profile and regenerative potential. The review highlights the mechanisms of action and results of clinical use of this combination. Uridine monophosphate, B vitamins, folic acid are involved in metabolic processes, enhancing nerve regeneration. This contributes to the development of indirect (secondary) anal­gesic effect. In addition, the data of new studies indicate the ability of uridine monophosphate derivatives to impact purinergic P2Y receptors, which causes a direct analgesic and direct regenera­tive effect. Studies have demonstrated the clinical efficacy of this combination in the main types of peripheral neuropathic pain. The combination did not cause side effects and was well tolera­ted. There was a reduction or complete withdra­wal of concomitant analgesics against the background of improving the quality of life of patients. The combination of uridine, choline, vitamin B1, vitamin B6, vitamin B12, and folic acid is a very effective addition to the standard therapy of peripheral neuropathic pain of various genesis and rehabilitation after COVID-19.

“A PRE-EXPERIMENTAL STUDY TO ASSESS THE EFFECTIVENESS OF FOOT REFLEXOLOGY ON DIABETIC PERIPHERAL NEUROPATHIC PAIN AMONG PATIENTS WITH DIABETES FROM SELECTED URBAN COMMUNITY.”

According to the Diabetes Atlas 2006 published by the International Diabetes Federation,the number of people with diabetes is 40.9% in India is around 40.9 million is expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken. It is estimated that over half of people currently living with diabetes in the country are unionized, so there is a real urgency to increase awareness and knowledge of diabetes and its associated complications. Foot ulceration is the most frequently recognized complication,estimated to affect up to 26 million people with diabetes globally.India is home to the second largest number of diabetes cases (73 million in 2017) in the world. Diabetic peripheral neuropathy (DPN) affects 20% to 30% of patients with diabetes and is a significant cause of morbidity and mortality. Although the true prevalence of DPN is difficult to determine, it may be responsible for up to 75% of non-traumatic amputations.Therefore investigator has decided to undertake a study to assess the effectiveness of foot reflexology on diabetic peripheral neuropathic pain among patients with diabetes from selected urban community and objective of the study was to compare the level of diabetic peripheral neuropathic pain before and after the intervention of foot reflexology among patients with diabetes