Use of kersetin and fisetin flavonoids in combination with pregabalin and gabapentin in the treatment of neuropathic pain.

We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain.

Examination of the effects of vitexin and vitexin-loaded solid lipid nanoparticles on neuropathic pain and possible mechanisms of action.

This research aims to investigate the possible antiallodynic and antihyperalgesic effects of pure vitexin and vitexin-loaded solid lipid nanoparticles (SLN) on neuropathic pain and the pathways mediating these effects. Chronic constriction nerve injury was induced in female rats, and the effects of vitexin at the doses of 5, 10, 20, 40 mg/kg were evaluated. Ketanserin, ondansetron, WAY-100635, yohimbine and bicuculin, which are antagonists of receptors on pain pathways. were used to examine the mechanisms of the effects of vitexin. Pure vitexin exhibited antiallodynic activity at all administered doses, whereas antihyperalgesic activity was not observed at 5 mg/kg vitexin dose. SLN formulation was prepared with 5 mg/kg vitexin, the lowest dose. Vitexin-loaded formulation significantly increased antiallodynic and antihyperalgesic effects. Ondansetron, WAY-100635, yohimbine, and bicuculine antagonized the antiallodynic and antihyperalgesic effects of vitexin. So, it was concluded that serotonin (5-hydroxtryptamine, 5-HT) receptor subtypes 5-HT3 and 5-HT1A, alpha-2 adrenergic, and γ-Aminobutyric acid type A (GABA-A) receptors are involved in the antiallodynic and antihyperalgesic activity of vitexin. In conclusion, vitexin and vitexin-loaded formulation have the potential for clinical use in neuropathic pain management, and different pain pathways contributed to this effect. And also, it is thought that vitexin-loaded SLN formulation is more effective than pure vitexin, which will provide an advantage in treatment.

Otolaryngology-Specific Symptoms May Be Highly Observed in Patients With a History of Covid-19 Infection After Inactivated Coronavirus Vaccination.

OBJECTIVE: To evaluate the otolaryngology-specific symptoms that occur after receiving the Covid-19 vaccine and its possible side effects in patients who had Covid-19 infection in the last 6 months before the vaccination. PATIENTS AND METHODS: The study comprised 3383 health care workers who were vaccinated against Covid 19. After excluding, the study was conducted with 1710 (51%) participants who agreed to answer the study questions. The participants were divided into 2 groups according to the history of Covid-19 positivity in the last 6 months before vaccination. The presence of symptoms related to otolaryngology practice, including cough, nasal congestion, rhinorrhea, sore throat, hearing loss, dizziness, loss of smell, loss of taste, ear pressure, and facial paralysis was recorded. RESULTS: The mean age of the study population was 35.79 ± 10.2 (19-71) years and 1454 (85%) of the patients had a history of Covid-19 infection in the last 6 months. Regarding otolaryngology-related symptoms, the most common complaints were rhinorrhea (4.4%), sore throat (3.2%), and nasal congestion (2.9%). The presence of smell and taste loss, nasal congestion, rhinorrhea, sore throat, and hearing loss was significantly more common in patients with a history of Covid-19 infection. CONCLUSIONS: The patients with a history of Covid-19 disease might have otolaryngology-specific symptoms more commonly than those without a history of Covid-19 disease in the last 6 months before vaccination.

Review: The nicotinic modulation of pain.

Pain is a physiological unpleasant sensation that associated with actual or potential tissue damage and affects the major part of human population. Numerous modulatory system control pain through a complex process. The drugs that regulate the modulators involving in this process are currently available; however, the studies to understand the process and develop new agents are still going on. In this review, it is aimed to relay information about how nicotinic receptors contribute the pain modulation. It is obvious that a wide variety of nicotinic receptors is located in both peripheral and central areas. Among these receptors α7, α4ß2 and α9α10 receptor subtypes draw attention in terms of pain modulation. The fact that different receptor subtypes involve in different processes of different pain conditions leads to provide beneficial results from the agonism of α7, α4ß2 and antagonism of α9α10. The major restraint of the usage of nAChR agonists is their adverse effects. However, nowadays, the side effects are reduced by the clinical developments. Additionally, positive allosteric modulators that amplify the effectiveness of nAChR ligands are in demand.