Ajeet Kumar Singh

Anti‐Nociceptive Effect of Resveratrol During Inflammatory Hyperalgesia via Differential Regulation of pro‐Inflammatory Mediators

Sensitization of nociceptive neurons by inflammatory mediators leads to hypersensitivity for normal painful stimuli which is termed hyperalgesia. Oxidative stress is an essential factor in pathological pain; therefore, antioxidants qualify as potential anti‐hyperalgesic agents. The present study examines the efficacy of the natural antioxidant resveratrol in complete Freunds adjuvant (CFA) induced hyperalgesic rats. Thermal hyperalgesia was measured at different time points by paw withdrawal latency test and confirmed by c‐Fos expression in spinal dorsal horn. The impact of resveratrol treatment on inflammatory mediators at peripheral (paw skin) and central (spinal cord) sites was determined during early (6 h) as well as late phase (48 h) of hyperalgesia. Intraplanter injection of CFA increased the level of cytokines IL‐1β, TNF‐α and IL‐6 as well as inflammatory enzymes COX‐2 and iNOS in paw skin in both phases. In case of spinal cord, the level of COX‐2 was found to be elevated in both phases, whereas iNOS could not be detected. The cytokines were found to be elevated only in late phase in spinal cord. Administration of resveratrol (20 mg/kg) shifted the level of all inflammatory mediators towards normal, except cytokines in paw skin. The present study suggests that the anti‐nociceptive effect of resveratrol is implicated at both peripheral and central sites in a tissue specific manner. Copyright

Recent development in antihyperalgesic effect of phytochemicals: anti-inflammatory and neuro-modulatory actions

IntroductionPain is an unpleasant sensation triggered by noxious stimulation. It is one of the most prevalent conditions, limiting productivity and diminishing quality of life. Non steroidal anti inflammatory drugs (NSAIDs) are widely used as pain relievers in present day practice as pain is mostly initiated due to inflammation. However, due to potentially serious side effects, long term use of these antihyperalgesic drugs raises concern. Therefore there is a demand to search novel medicines with least side effects. Herbal products have been used for centuries to reduce pain and inflammation, and phytochemicals are known to cause fewer side effects. However, identification of active phytochemicals of herbal medicines and clear understanding of the molecular mechanism of their action is needed for clinical acceptance.Materials and methodsIn this review, we have briefly discussed the cellular and molecular changes during hyperalgesia via inflammatory mediators and neuro-modulatory action involved therein. The review includes 54 recently reported phytochemicals with antihyperalgesic action, as per the literature available with PubMed, Google Scholar and Scopus.ConclusionCompounds of high interest as potential antihyperalgesic agents are: curcumin, resveratrol, capsaicin, quercetin, eugenol, naringenin and epigallocatechin gallate (EGCG). Current knowledge about molecular targets of pain and their regulation by these phytochemicals is elaborated and the scope of further research is discussed.

Resveratrol alleviates inflammatory hyperalgesia by modulation of reactive oxygen species (ROS), antioxidant enzymes and ERK activation

ObjectivesImpact of ROS in development of hyperalgesia has recently motivated scientists to focus on ROS as novel target of anti-hyperalgesic interventions. However, role of ROS in molecular signaling of hyperalgesia is still poorly understood. The present study is aimed to analyze the effect of dietary antioxidant resveratrol on antioxidant defense system, ROS level and TNFR1–ERK signaling pathway during early and late phase of inflammatory hyperalgesia.Methods and materialsHyperalgesia was assessed by paw withdrawal latency test in complete Freund’s adjuvant-induced hyperalgesic rats. Activities of antioxidant enzymes were measured by in-gel assays, ROS level was measured by DCFH2DA, and expression of pERK, ERK and TNFR1 was estimated by Western blotting.ResultsAnti-hyperalgesic effect of resveratrol was observed by paw withdrawal latency test. ROS level was increased in paw skin as well as spinal cord during early phase which was further increased in paw skin, but remained constant in spinal cord up to late phase. Resveratrol differentially regulated the activities of SOD, catalase and GPx in paw skin as well as spinal cord of hyperalgesic rats in both phases. Activities were normalized back showing anti-hyperalgesic effect of resveratrol. Upregulated ERK signaling was modulated by resveratrol, whereas TNFR1 level remained unchanged.ConclusionOverall results suggest that resveratrol alleviates inflammatory hyperalgesia by downregulation of ERK activation, modulation of ROS and differential regulation of antioxidant enzymes during early and late phases.

Activation of ERK signalling by Src family kinases (SFKs) in DRG neurons contributes to hydrogen peroxide (H2O2)-induced thermal hyperalgesia

Abstract Concomitant generation of reactive oxygen species during tissue inflammation has been recognised as a major factor for the development and the maintenance of hyperalgesia, out of which H2O2 is the major player. However, molecular mechanism of H2O2 induced hyperalgesia is still obscure. The aim of present study is to analyse the mechanism of H2O2-induced hyperalgesia in rats. Intraplantar injection of H2O2 (5, 10 and 20 µmoles/paw) induced a significant thermal hyperalgesia in the hind paw, confirmed by increased c-Fos activity in dorsal horn of spinal cord. Onset of hyperalgesia was prior to development of oxidative stress and inflammation. Rapid increase in phosphorylation of extracellular signal regulated kinase (ERK) was observed in neurons of dorsal root ganglia after 20 min of H2O2 (10 µmoles/paw) administration, which gradually returned towards normal level within 24 h, following the pattern of thermal hyperalgesia. The expression of TNFR1 followed the same pattern and colocalised with pERK. ERK phosphorylation was observed in NF-200-positive and -negative neurons, indicating the involvement of ERK in C-fibres as well as in A-fibres. Intrathecal preadministration of Src family kinases (SFKs) inhibitor (PP1) and MEK inhibitor (PD98059) prevented H2O2 induced augmentation of ERK phosphorylation and thermal hyperalgesia. Pretreatment of protein tyrosine phosphatases (PTPs) inhibitor (sodium orthovanadate) also diminished hyperalgesia, although it further increased ERK phosphorylation. Combination of orthovanadate with PP1 or PD98059 did not exhibit synergistic antihyperalgesic effect. The results demonstrate SFKs-mediated ERK activation and increased TNFR1 expression in nociceptive neurons during H2O2 induced hyperalgesia. However, the role of PTPs in hyperalgesic behaviour needs further molecular analysis.

Wild Relatives of Cultivated Plants in India. A Reservoir of Alternative Genetic Resources and More, A.K. Singh, Springer (2017) 309 pp., Price 156.99 £, ISBN: 9789811051166

Wild relatives of cultivated plants are the treasure trove of genetic resources for crop improvement and dietary diversification. Especially, they are crucial for conferring diseases resistance and abiotic stress tolerance (such as drought, flood, heat-shock, salinity, etc.) in cultivated crops and thereby breeding next generation of climate smart crops (i.e. climate resilient crops) for futuristic climatic conditions. Unfortunately, most of the wild relatives of crop plants across the world are being neglected and underutilized, without recognizing its real potential. In this backdrop, the book herein review titled “Wild Relatives of Cultivated Plants in India: A Reservoir of Alternative Genetic Resources and More”, authored by Anurudh Kumar Singh, National Bureau of Plant Genetic Resources, New Delhi, India is a timely and topical endeavor to provide a vivid account of more than 958 species of wild relatives of cultivated plants in India along with their occurrence, distribution, current status, as well as their future potential for breeding program and dietary diversification. Moreover, the author has also explored the additional utility of such crop species for ecosystem restoration, phytoremediation and soil carbon sequestration in detail. Here we distill the essence of this 309-page book for the better comprehension and understanding for a wide range of potential readers like graduate students and doctoral researchers in agricultural and environmental sciences, agronomist, plant breeders, as well as various national and international policy makers and regulatory agencies.

A Class of Exponential Chain Type Estimator for Population Mean With Imputation of Missing Data Under Double Sampling Scheme

This paper aims to deal with the problem of non-response, by s uggesting an exponential chain type class of imputation technique and corresponding point estimator in double samp ling has been proposed for estimating finite population mean of the study variable when the information on another additional auxili ary variable is available along with the main auxiliary vari able. The bias and mean square error of the proposed strategy have been obtaine d. Th oretical and empirical studies have been done to demon strate the supremacy of the proposed strategy with respect to the strat egies which utilize the information on one and two auxiliary characteristics.

Model-based study of families of exponential-type estimators in presence of non response

ABSTRACT Among other types of non sampling errors, non response error (NRE) is an inherent component of any sample survey, which is supposed to be given much attention during the designing and execution stages. With increasing awareness of these estimators, therefore, there is an urge for the development of suitable techniques for controlling them. This article proposes two families of estimators for population mean in the presence of non response and discuses various properties under model approach, namely polynomial regression model. The families include some existing estimators. Comparison of efficiencies along with the robustness of the estimators under misspecification of models has been empirically discussed.