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The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is imperfectly understood. Recent studies reported that small-fiber polyneuropathy (SFPN) is common in fibromyalgia, a condition commonly comorbid with IC/BPS.

A systematic review of original research articles was conducted to evaluate the safety and efficacy of lidocaine infusion in the treatment of adult patients with chronic neuropathic pain.

Two decades after reports of the anti-pruritic effects of botulinum neurotoxins (BoNTs), there is still no approved product for the anti-itch indication of BoNTs, and most clinical case reports still focus on the off-label use of BoNTs for various itchy conditions. Few randomized clinical trials have been conducted with controversial results, and the beneficial effects of BoNTs against itch are mainly based on case studies and case series. These studies are valuable in presenting the potential application of BoNTs in chronic pruritic conditions, but due to the nature of these studies, they are categorized as providing lower levels of evidence or lower grades of recommendation. To obtain approval for the anti-pruritic indication of BoNTs, higher levels of evidence are required, which can be achieved through conducting large-scale and well-designed studies with proper control groups and established careful and reliable primary and secondary outcomes. In addition to clinical evidence, presenting the mechanism-based antipruritic action of BoNTs can potentially strengthen, accelerate, and facilitate the current efforts towards further investments in accelerating the field towards the potential approval of BoNTs for itchy conditions. This review, therefore, aimed to provide the state-of-the-art mechanisms underlying the anti-itch effect of BoNTs from basic studies that resemble various clinical conditions with itch as a hallmark. Evidence of the neuronal, glial, and immune modulatory actions of BoNTs in reducing the transmission of itch are presented, and future potential directions are outlined.

Transdermal therapeutic systems (TTSs) enable convenient dosing in drug therapy. Modified silicone-polymer-based patches are well-controlled and cost-effective matrix diffusion systems. In the present study, we investigated the substance release properties, skin penetration, and analgesic effect of this type of TTS loaded with low-dose capsaicin. Release properties were measured in Franz diffusion cell and continuous flow-through cell approaches. Capsaicin was detected with HPLC-UV and UV spectrophotometry. Raman spectroscopy was conducted on human skin samples exposed to the TTS. A surgical incision or carrageenan injection was performed on one hind paw of male Wistar rats. TTSs were applied to the epilated dorsal skin. Patches were kept on the animals for 6 h. The thermal hyperalgesia and mechanical pain threshold of the hind paws were detected. Patches exhibited controlled, zero-order kinetic capsaicin release. According to the Raman mapping, capsaicin penetrated into the epidermis and dermis of human skin, where the target receptors are expressed. The thermal pain threshold drop of the operated rat paws was reversed by capsaicin treatment compared to that of animals treated with control patches. It was concluded that our modified silicone-polymer-based capsaicin-containing TTS is suitable for the relief of traumatic and inflammatory pain.

Capsaicin is a naturally occurring alkaloid derived from chili pepper which is responsible for its hot, pungent taste. It exerts multiple pharmacological actions, including pain-relieving, anti-cancer, anti-inflammatory, anti-obesity, and antioxidant effects. Previous studies have shown that capsaicin significantly affects the contractility and automaticity of the heart and alters cardiovascular functions. In this study, the effects of capsaicin were investigated on voltage-gated ion currents in rabbit ventricular myocytes. Capsaicin inhibited rapidly activated () and slowly activated () K currents and transient outward () K current with IC values of 3.4 µM,14.7 µM, and 9.6 µM, respectively. In addition, capsaicin, at higher concentrations, suppressed voltage-gated Na and Ca currents and inward rectifier current with IC values of 42.7 µM, 34.9 µM, and 38.8 µM, respectively. Capsaicin inhibitions of , , , , , and were not reversed in the presence of capsazepine (3 µM), a TRPV1 antagonist. The inhibitory effects of capsaicin on these currents developed gradually, reaching steady-state levels within 3 to 6 min, and the recoveries were usually incomplete during washout. In concentration-inhibition curves, apparent Hill coefficients higher than unity suggested multiple interaction sites of capsaicin on these channels. Collectively, these findings indicate that capsaicin affects cardiac electrophysiology by acting on a diverse range of ion channels and suggest that caution should be exercised when capsaicin is administered to carriers of cardiac channelopathies or to individuals with arrhythmia-prone conditions, such as ischemic heart diseases.

Chronic pain and depression affect millions of people worldwide, and their comorbidity tends to exacerbate the severity of each individual condition. Intersecting brain regions and molecular pathways could probably explain the unique yet complex bidirectional relationship between these two disorders. Recent studies have found that inflammatory reactions, frequently identified in both chronic pain and depression, stimulate certain enzymes in the kynurenine pathway, while concurrently suppressing others. Kynurenine, a major tryptophan derivative, and its metabolites have been implicated in several inflammation-associated pain syndromes and depressive mood disorders. Due to inflammation, 95% of tryptophan is metabolized via the kynurenine pathway, which drives the reaction towards the production of metabolites that have distinct roles in the pathophysiology of these disorders. Diminished levels of the neuroprotective metabolite, kynurenic acid (KYNA), and elevated levels of the neurotoxic metabolite, quinolinic acid (QUIN), have been frequently identified in human patients formally diagnosed with these disorders, as well as animal models commonly used in medical research. This review not only explores the epidemiology of comorbid chronic pain and depression, but also highlights the involvement of kynurenine and its metabolites, specifically KYNA and QUIN, in these pervasive conditions.

Transient Receptor Potential Melastatin 8 (TRPM8) from the melastatin TRP channel subfamily is a non-selective Ca-permeable ion channel with multimodal gating which can be activated by low temperatures and cooling compounds, such as menthol and icilin. Different conditions such as neuropathic pain, cancer, overactive bladder syndrome, migraine, and chronic cough have been linked to the TRPM8 mode of action. Despite the several potent natural and synthetic inhibitors of TRPM8 that have been identified, none of them have been approved for clinical use. The aim of this study was to discover novel blocking TRPM8 agents using automated patch clamp electrophysiology combined with a ligand-based virtual screening based on the SwissSimilarity platform. Among the compounds we have tested, nebivolol and carvedilol exhibited the greatest inhibitory effect, with an IC of 0.97 ± 0.15 µM and 9.1 ± 0.6 µM, respectively. This study therefore provides possible candidates for future drug repurposing and suggests promising lead compounds for further optimization as inhibitors of the TRPM8 ion channel.

Cisplatin-induced peripheral neuropathy is a common complication of cisplatin therapy, which develops in most patients with lung cancer. There are no effective preventive measures and once it occurs there is no effective therapy, except symptomatic. In this study, we aimed to assess the effect of transcutaneous electrical nerve stimulation (TENS) therapy on the pain intensity and the quality of life of patients with cisplatin-induced neuropathy. A prospective cohort study was performed from 2013 to 2018, at the Clinical Center of Serbia. After the initial evaluation of 106 newly diagnosed patients with lung cancer, 68 patients did not have peripheral neuropathy. These 68 patients continued in the study and started the cisplatin chemotherapy. Forty of these patients developed cisplatin-induced neuropathy, which was manifested by neuropathic symptoms and proven by ENG examination. All patients with cisplatin-induced neuropathy were treated with TENS therapy. Their neuropathic pain and quality of life were evaluated using the following questionnaires at diagnosis, after cisplatin therapy and after four weeks of TENS use: DN4, VAS scale, EORTC QLQ-C30 and FACT-L. Two thirds (68%) of the patients with cisplatin-induced neuropathy were male and the majority were smokers (70%). Adenocarcinoma was the most common (38%), followed by squamous (33%) and small-cell carcinoma (28%). The application of TENS therapy had a positive effect on reducing the neuropathic pain and increasing the quality of life for patients with painful cisplatin-induced neuropathy. The VAS and DN4 scores significantly decreased after TENS therapy, in comparison to its values after cisplatin therapy ( < 0.001). After TENS therapy, patients had significantly higher values in most of the domains of EORTC QLQ-C30 and FACT- L, in comparison with the values after cisplatin therapy ( < 0.001). The application of TENS therapy has a positive effect on reducing neuropathic pain and increasing the quality of life for patients with lung cancer and cisplatin-induced neuropathy.

Offset analgesia describes the effect of a slightly reduced nociceptive stimulus, resulting in a disproportionate large reduction in the pain perception. This effect may be associated with descending pain inhibition, but parameters influencing this phenomenon are poorly understood.