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This paper presents an efficient numerical technique for solving a class of time‐fractional diffusion equation. The time‐fractional derivative is described in the Caputo form. The L1 scheme is used for discretization of Caputo fractional derivative and a collocation approach based on sextic B‐spline basis function is employed for discretization of space variable. The unconditional stability of the fully‐discrete scheme is analyzed. Two numerical examples are considered to demonstrate the accuracy and applicability of our scheme. The proposed scheme is shown to be sixth order accuracy with respect to space variable and (2 − α)‐th order accuracy with respect to time variable, where α is the order of temporal fractional derivative. The numerical results obtained are compared with other existing numerical methods to justify the advantage of present method. The CPU time for the proposed scheme is provided. [ABSTRACT FROM AUTHOR]

This paper is concerned with the development of a high order numerical technique for solving time‐fractional reaction–diffusion equation. The fractional derivative in the governing equation is described in the Caputo sense and a collocation method based on quintic B‐spline basis function is used to discretize the space variable. The stability and convergence analysis of the method are investigated, and it is shown that the proposed method converges to the exact solution of the problem with order of convergence O(Δt2 − α + Δx4), where α is the order of fractional derivative (0 < α < 1). Three test problems are considered to illustrate the efficiency and accuracy of present numerical scheme and to verify the theoretical result. It is shown that the order of fractional derivative has a profound effect on the solution of time‐fractional reaction–diffusion equation. [ABSTRACT FROM AUTHOR]

Rationale: Ropanicant (SUVN-911) (3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo (3.1.0) hexane hydrochloride) is a novel α4β2 nicotinic acetylcholine receptor (nAChR) antagonist being developed for the treatment of depressive disorders., Objectives: Pharmacological and neurochemical characterization of Ropanicant to support a potential molecule for the treatment of depressive disorders., Methods: Ropanicant was assessed for antidepressant-like activity using the rat forced swimming test (FST) and differential reinforcement of low rate -72 s (DRL-72 s). Alleviation of anhedonia was assessed in chronic mild stress model using sucrose preference test. To understand the mechanism of action, serotonin levels, ionized calcium-binding adaptor molecule 1 (Iba1), and brain-derived neurotrophic factor (BDNF) were determined. The onset of antidepressant-like activity was determined using the reduction in submissive behavior assay. The effects on cognition and sexual functions were assessed using the object recognition task and sexual dysfunction assay respectively. Interaction of Ropanicant, TC-5214, and methyllycaconitine (MLA) with citalopram was investigated individually in mice FST., Results: Ropanicant exhibited antidepressant like properties in the FST and DRL-72 s. A significant reduction in anhedonia was observed in the sucrose preference test. Oral administration of Ropanicant produced a significant increase in serotonin and BDNF levels, with a reduction in the Iba1 activity. The onset of antidepressant like effect with Ropanicant was within a week of treatment, and was devoid of cognitive dulling and sexual dysfunction. While Ropanicant potentiated the effect of citalopram in FST, such an effect was not observed with MLA or TC-5214., Conclusions: Preclinical studies with Ropanicant support the likelihood of its therapeutic utility in the treatment of depressive disorders., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Memory deficit is a co-morbid disorder in patients suffering from neuropathic pain. Gabapentin and pregabalin (gabapentinoids) are among the widely prescribed medications for the treatment of neuropathic pain. Memory loss and sedation are the commonly reported side effects with gabapentinoids. Improving the cognitive functions and attenuating drug-induced side effects may play a crucial role in the management of pain., Methods: We evaluated the effects of 5-HT6 receptor antagonists on the memory deficits associated with neuropathy. We also studied the effects of 5-HT6 receptor antagonists on the side effects, and the analgesic effects of gabapentinoids., Results: 5-HT6 receptor antagonists attenuated the cognitive deficits in neuropathic rats. Neuropathic rats co-treated with 5-HT6 receptor antagonist and gabapentinoids showed improvement in memory. 5-HT6 receptor antagonists enhanced the analgesic effects of gabapentinoids but had no effect on the motor side effects. The observed effects may not be due to pharmacokinetic interactions., Conclusions: 5-HT6 receptor antagonist attenuate the cognitive deficits associated with neuropathy, and this effect is also seen when co-treated with gabapentinoids. Since, 5-HT6 antagonists improved the effectiveness of gabapentinoids, reduction in the dosage and frequency of gabapentinoids treatment may reduce the side effects. Combining 5-HT6 receptor antagonist with gabapentinoids may offer a novel treatment strategy for neuropathic pain., (Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

α4β2* neuronal nicotinic acetylcholine receptor are ligand-gated ion channels and widely expressed throughout the central and peripheral nervous system. α4β2* neuronal nicotinic acetylcholine receptor play crucial role in pain signaling via modulation of multiple neurotransmitters like acetylcholine, dopamine, γ-amino butyric acid (GABA) and norepinephrine. Both spinal and supraspinal pathways are involved in the mechanisms by which α4β2* neuronal nicotinic acetylcholine receptor ligands modulate the neuropathic and inflammatory pain. Selective α4β2* neuronal nicotinic acetylcholine receptor ligands are being developed for the treatment of neuropathic and inflammatory pain as they show considerable efficacy in a wide range of preclinical pain models. Agonists/partial agonists of α4β2* neuronal nicotinic acetylcholine receptor show efficacy in animal models of pain and their anti-nociceptive properties are blocked by nicotinic antagonists. Positive allosteric modulators are being developed with the aim to increase the potency or therapeutic window of agonists/partial agonists. Accumulating evidences suggest that anti-nociceptive effects of nicotinic acetylcholine receptor ligands may not be mediated solely by α4β2* neuronal nicotinic acetylcholine receptor. We have also reviewed the stage of clinical development of various α4β2* neuronal nicotinic acetylcholine receptor ligands., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: The most commonly used Von Frey filaments are productive in evaluating behavioral responses of neuropathic pain in preclinical and clinical research. To reduce the potential experimenter bias, automated instruments are being developed for behavioral assessment. In preclinical research, neuropathic pain models of nerve injury with varied etiology like partial sciatic nerve ligation (PNL), chronic constricted injury (CCI) and spinal nerve ligation (SNL) are employed to screen the analgesic drugs to treat symptoms like allodynia and hyperalgesia. The current study was aimed to validate and compare conventionally used Von Frey monofilaments and automated dynamic plantar aesthesiometer using three different pain models., Methods: PNL, CCI and SNL rats were used to compare and validate the assessment of neuropathic pain using Von Frey monofilaments and automated dynamic plantar aesthesiometer., Results: Mechanical allodynia was assessed at various time points to mimic drug testing conditions in neuropathic pain models and anticipated to observe reliable and reproducible paw withdrawal threshold measurements across these models. Consistent paw withdrawal thresholds were observed in all the three models of neuropathic pain with Von Frey monofilaments, whereas variable paw withdrawal thresholds were noticed in PNL and CCI models but not in SNL model with dynamic plantar aesthesiometer., Discussion: Manually used Von Frey filaments can be used in assessment of mechanical allodynia in all the three models, whereas dynamic plantar aesthesiometer is suitable for assessing mechanical allodynia in SNL but not in PNL and CCI models. The reason for variable paw withdrawal thresholds during assessment of mechanical allodynia in PNL and CCI models with dynamic plantar aesthesiometer may be due to the paw deformity and change in foot posture., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Nerve injury, diabetes and cancer therapies are often associated with painful neuropathy. The mechanism underlying neuropathic pain remains poorly understood. The current therapies have limited efficacy and are associated with dose-limiting side effects. Compounds which act at nicotinic acetylcholine receptors have also been reported to show antinociceptive activity. Among those, tebanicline (ABT-594) a potent nicotinic acetylcholine receptor agonist demonstrated analgesic effects across a broad range of preclinical models of nociceptive and neuropathic pain. Another nicotinic acetylcholine receptor agonist, 5-[(1R,5S)-3,6-Diazabicyclo[3.2.0]heptan-6-yl]nicotinonitrile (A-366833) from the same group produced significant antinociceptive effects in writhing pain (abdominal constriction), acute thermal pain (hot box), persistent chemical pain (formalin induced) and neuropathic pain. In the present study, we have demonstrated the efficacy of A-366833 in rat models of chronic constriction injury, partial sciatic nerve ligation, spinal nerve ligation, diabetes, chemotherapy induced neuropathic pain and complete Freund's adjuvant induced inflammatory pain. A-366833 (1, 3 and 6 mg/kg) produced significant antihyperalgesic effects in partial sciatic nerve ligation, chronic constriction injury and spinal nerve ligation models. In the diabetic and chemotherapy induced neuropathic models compound exerted antinociceptive activity and reduction in the mechanical hyperalgesia was observed. A-366833 dose dependently attenuated mechanical hyperalgesia in complete Freund's adjuvant induced inflammatory pain model. These results demonstrated broad-spectrum antinociceptive properties of A-366833 in both neuropathic and inflammatory pain models., (Copyright © 2011. Published by Elsevier B.V.)