International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
logo
slider
slider
slider
slider
Bootstrap Slider

Indexed and Abstracted in: Crossref, CAS Abstracts, Publons, Google Scholar, Open J-Gate, ROAD, Indian Citation Index (ICI), ResearchGATE, Ulrich's Periodicals Directory, WorldCat (World's largest network of library content and services)

Search Articles

Track manuscript

Full Html

IJCRR - 4(1), January, 2012

Pages: 34-43

Print Article   Download XML  Download PDF

ANTINOCICEPTIVE EFFECTS OF DIAZOXIDE IN RODENT MODEL OF CHRONIC PAIN INDUCED BY
CHRONIC CONSTRICTION NERVE INJURY

Author: Deshmukh A. B., Patel J. K., Prajapati A. R., Patel K. S., Jadav R. J.

Category: Healthcare

Abstract:Aim: Previous studies show that neuropathic pain is refractory against conventional analgesics and thus novel medicaments are desired for the treatment. Activated K+ channels are associated with reducing inappropriate or excessive neuronal activity. The aim of this study was to investigate the possible analgesic effects of potassium channel opening on neuropathic pain. Therefore, the present study was designed to investigate whether potassium channel activator can generate qualitative analgesic effects on the acute pain induced by thermal and mechanical stimulation. Methods: The effect of diazoxide at the dose of 200 mg/kg on acute thermal and mechanical nociception were assessed by sensory testing like spontaneous pain, mechanical hyperalgesia, tactile as well as cold allodynia in chronic constriction injury (CCI) induced pain in rat. Results: After CCI surgery, the rats developed neuropathic pain syndrome. Behavioral studies demonstrated that rats with the CCI experienced spontaneous pain, dynamic allodynia and mechanical hyperalgesia which were significantly different from the sham group. Treatment with diazoxide decreased significantly the withdrawal durations in all sensory tests. Conclusion: The present study indicates that activity of K+ channel may contribute significantly to the development of central sensitization-mediated pain and suggests that K+
openers may be an important molecular target for the treatment of chronic pain of neuropathic origin.

Keywords: Neuropathic pain, Diazoxide, Potassium channels, Chronic constriction injury, sensory test

Full Text:

INTRODUCTION
Neuropathic pain is one of the most significant health problems in the world. Neuropathic (neurogenic) pain is defined by IASP as pain caused by a lesion or dysfunction of the nervous system (1). It is characterized by inappropriate spontaneous or excessive neuronal activity in response to physiological stimuli. Chronic pain is one of most common reasons for hospital visits so it should be considered to be a disease rather than just a symptom. Recent advances in molecular biology techniques and the subsequent discoveries of key molecules involved in pain production, have clearly contributed to better understanding acute pain (2-5), by which the molecular multiple mechanisms underlying chronic pain can be fully clarified. Proper diagnosis and early treatment are often found to be difficult in neuropathic pain, because it is quite different from other types of pain, such as nociceptive (or physiological) or inflammatory pain and it is irreversible, even when the underlying cause has been rectified (3). Also, the occurrence of neuropathic pain is commonly as a secondary symptom in diseases (e.g. diabetes, cancer, and herpes zoster infection) or as a side effect of chemotherapeutic treatments (4, 6-8). The management of this disorder is achieved by various classes of drugs that are capable of dampening neuronal excitability. Examples may be voltagegated sodium channel blockers (carbamazepine, phenytoin, lamotrigine and topiramate), voltage-operated calcium channel modulators (ethosuximide, gabapentin, levetiracetam) and modulators of inhibitory GABAergic neurotransmission (benzodiazepines, vigabatrin and tiagabine). Of these, the approved drugs for the treatment of neuropathic pain are gabapentin, and carbamazepine and lamotrigine has demonstrated efficacy for neuropathic pain in clinical trials (9). Various drugs with sodium channel blocking actions preferentially suppress thermal nociception which may be partly explained by the local anesthetic action of sodium channel blocking agents and differential sensitivities to local anesthetics of the fibers activated by thermal and mechanical nociception (10). However, a number of issues regarding this treatment, including the effective, meaningful drug dose range, the durability of pain-relief effects leading a poor treatment to patient with currently available drugs. So there is a need for new agents with their novel mechanism for the treatment of neuropathic pain. Potassium (K+ ) channel opening is one potential mechanism that has not yet been exploited for neuropathic pain. Activated K+ channels are associated with reducing inappropriate or excessive neuronal activity (11). Therefore, the present study was designed to investigate whether potassium channel activation generate qualitative analgesic effects on the acute pain induced by thermal and mechanical stimulation.

MATERIALS AND METHODS
Animals
Wistar-kyoto male rats of 8 weeks age with the body weight range from 250-300 gms were procured from Central Animal Facility, Nootan pharmacy college, Visnagar, India. They were maintained in essential condition of controlled temperature (<30? C) and humidity (< 70%) with 12 hour day and night cycle according to the norms of CPCSEA.

Chronic Constriction Injury (CCI)
CCI surgery was carried out as described (12). Rats were anesthetized with combination of ketamine and xylazine and a 7-mm segment of the left common sciatic nerve was exposed at the mid-thigh level, Proximal to the sciatic trifurcation, about 7 mm of nerve was freed of adhering tissue and 4 ligatures (4-0 silk) were tied loosely around at about 1 mm spacing. Ligatures were tied loosely enough so that, on visual inspection, blood flow was not obstructed. The incision was closed in layers. Post seven days of healing nociceptive test was done followed by behavioural assessment.

Sham Surgery: Same surgical procedure was followed in six animals except the removal part/whole of kidney and kidneys were touched with forceps and threads.

Drugs and Chemicals:
Diazoxide was procured from Ranbaxy Research laboratories, India. DMSO was procured from Veeraj Associates Ahmedabad, India. Ketamine and Xylazine were purchased from Visnagar, India.

Grouping of animals:
After one week of CCI in animals they divided in to three groups: Group 1: sham group, Group 2: CCI with drug (Diazoxide) and Group 3: CCI with vehicle (CCI group).

Treatment with diazoxide:
Animals in group 2 were treated with Diazoxide at the dose of 200 mg/kg (dissolved in DMSO 25mg/ml) by oral route once a day for 7 days, while that of group 3 were treated with vehicle (DMSO).

Sensory testing using nociceptive assay in CCI rats:
Four nociceptive assays aimed to determine the severity of neuropathic responses namely allodynia and hyperalgesia were performed. Estimation of parameters at basal, day 1, day3, day 5 and day 7.
1. Spontaneous pain
2. Dynamic allodynia
3. Cold allodynia
4. Mechanical hyperalgesia

Spontaneous pain:
Spontaneous pain was assessed for total period of 5 min as described (13). The operated rats were placed into the observation cage 5 cm from working place. An initial acclimatization period of 10 min was given to each of rats. From each group total six rats were assessed. The test is based on recording of the cumulative duration that the rats hold its ipsilateral paw off the floor. The paw lifts associated with locomotion or body repositioning was not counted. The paw lifts in the absence of any overt external stimuli are associated with spontaneous pain, and are correlated of ongoing pain are counted.

Dynamic allodynia:
All of the operated rats were assessed for dynamic allodynic response according to the procedures described (14). The operated rats were placed into the observation cage 5 cm from working place. Lifting of the affected paw for finite period of time in response to mild stroking on the plantar region using cotton-bud is a positive dynamic allodynia. This stimulus is non-noxious to normal- behaviouring rats. The latency to paw withdrawal was then counted. If no paw withdrawal was shown within 15s, the test was terminated and animal were assigned withdrawal time. Hence 15s effectively represented no withdrawal.

Cold allodynia:
Application of cold (an acetone drop placed on the paw) in the on the plantar region (15) was used for estimating the withdrawal duration of cold allodynia. If no paw withdrawal was shown within 15s, the test was terminated and animal were assigned withdrawal time. Hence 15s effectively represented no withdrawal.

Mechanical hyperalgesia:
The operated rats were assessed for mechanical hyperalgesia sensitivity according to the procedure described (16). The initial set up was same as previous test. The measurement of hind paw withdrawal duration was done after mild pinprick stimulus to the mid plantar surface of the ipsilateral (left) hind paw. A withdrawal was defined as being abnormally prolonged if lasted at least 2s. The mean withdrawal duration was taken from a set of three responses.

Statistical analysis
All the data were expressed as mean ± s.e.m. The single treatment studies were analysed using unpaired t-test using graphPad Prism 5.0.

RESULTS
General observations
After CCI surgery, the rats developed neuropathic pain syndrome as previously described (12). Unusual gait and posture of the rats was observed as early as on the first day after surgery. The rats often raised the affected hind paws from the floor and hold them in a protected position. Frequent licks of the affected paws were seen. All the animals were in good health and the behavior was generally normal with no palsy or additional sensory dysfunction encountered. There was no significant difference among the weights of the three groups (data not shown).

Effects on Sensory testing:
Spontaneous pain:

After CCI surgery, the rats developed spontaneous pain which was found to be 191.67 ± 18.97 at the end of 7th day. There was a gradual elevation in the spontaneous pain from day 1 of surgery. Drug treatment at the dose of 200 mg/kg decreased the spontaneous pain. A gradual reduction was observed in animals of group 2 which was observed to be 58.33 ± 2.55 at the end of day 7 post treatment. There was a marked increase in the withdrawal duration in group 3 animals as the days progressed post surgery which was greatest at the end of day 7.

Dynamic allodynia:
Animals exhibited dynamic allodynia which was 72.67 ± 4.73 at the end of day 7, and was found to be reduced to 49.33 ± 0.51 in group 2. A significant difference was found in the withdrawal duration for dynamic allodynia between group 2 and group 3. Moreover sham operated animals of group 1 showed negligible duration of withdrawals, thus a significant difference was also observed between group 1 and group 3.

Cold allodynia:
Application of cold (an acetone drop placed on the paw) in the on the plantar region (15) was used for estimating the withdrawal duration of cold allodynia. If no paw withdrawal was shown within 15s, the test was terminated and animal were assigned withdrawal time. Hence 15s effectively represented no withdrawal.

Mechanical hyperalgesia:
The operated rats were assessed for mechanical hyperalgesia sensitivity according to the procedure described (16). The initial set up was same as previous test. The measurement of hind paw withdrawal duration was done after mild pinprick stimulus to the mid plantar surface of the ipsilateral (left) hind paw. A withdrawal was defined as being abnormally prolonged if lasted at least 2s. The mean withdrawal duration was taken from a set of three responses.

DISCUSSION
Painful stimuli are transferred to the CNS by the lateral spinothalamic tract. First order neurons transmitting pain impulses from the skin (Aδ and C fibres) enter the substantia gelatinosa of the dorsal horn via the dorsal roots. Second order neurons in the lateral spinothalamic tracts convey impulses associated with pain up to the nuclei of the ventroposterior thalamus where the painful impulses are integrated. From the thalamus, third order neurons convey the impulses up to the cerebral cortex, where subjective interpretation of pain is thought to occur (17). Neuropathic pains are disorders characterized by excessive neuronal activity. These disorders are currently managed by drugs that are capable of dampening neuronal excitability, including voltage-gated sodium channel blockers, voltage-operated calcium channel modulators and modulators of inhibitory GABAergic neurotransmission. However, these drugs are rarely 100% efficacious and their use is often associated with limiting side effects. Thus, there is a clear medical need for novel agents to treat these diseases. One potential mechanism that has not yet been exploited is potassium (K+ ) channel opening. A significant and growing body of genetic, molecular, physiological and pharmacological evidence now exists to indicate that KCNQ-based currents represent particularly interesting targets for the treatment of diseases such as epilepsy and neuropathic pain (11). Moreover, ATP-sensitive potassium (KATP) channels may be linked to mechanisms of pain after nerve injury, but remain underinvestigated in primary afferents so far. A study characterized these channels in dorsal root ganglion (DRG) neurons, and tested whether they contribute to hyperalgesia after spinal nerve ligation (SNL). Following SNL, this channel activity was suppressed in large neurons from hyperalgesic rats. In large neurons, selective inhibition of whole-cell ATPsensitive potassium channel current (IK(ATP)) by glibenclamide depolarized resting membrane potential (RMP). The contribution of this current to RMP was also attenuated after painful axotomy. These findings indicate that functional KATP channels are present in normal DRG neurons, wherein they regulate RMP. Alterations of these channels may be involved in the pathogenesis of neuropathic pain following peripheral nerve injury. Their biophysical and pharmacological properties are preserved even after axotomy, suggesting that KATP channels in primary afferents remain available for therapeutic targeting against established neuropathic pain (18). A study has demonstrated that KATP channel opening results in decreased excitability, attenuated neurotransmission, and possibly antihyperalgesia. Therefore, these channels in DRG neurons provide novel opportunities for therapeutic targeting using KATP channel openers (19) or CaMKII activators (20, 21) as analgesics in neuropathic pain. We tested a hypothesis that K+ channel opener like diazoxide administration may decline the pain due to decreased excitability of the hyperactive nerves and improve the pain condition to which we obtained consistent results. While our ultimate goal was to elucidate the role of K + channels in neuropathic pain, we employed a well-established chronic constriction injury model (CCI) in this study to investigate effects of our approach. CCI also  known as Bennett model is a rat model of painful peripheral mononeuropathy (12). CCI rats show behavioral signs of spontaneous pain such as mild to moderate autotomy, guarding, excessive licking and limping of ipsilateral hind paw, and avoidance of placing weight on the injury side. Hyperalgesia due to noxious thermal and mechanical stimuli is detectable, as are cold allodynia and tactile (12, 22). All pain signs last for the entire duration of the study. CCI induced spontaneous pain which was characterized by signs of paw guarding, lifting, and limping, excessive grooming and biting, changes in exploratory behavior, weight bearing. In addition, evoked pain (allodynia and thermal hyperalgesia) to thermal or mechanical stimuli was observed in CCI group although it was at different levels. There was a significant increase in the all the four Sensory parameters like spontaneous pain, dynamic allodynia, cold allodynia and mechanical hyperalgesia as compared to the animals of sham group. The parameters were noted at the interval of 1 day right from basal, day 1 post surgery, day 3, 5 and 7 post surgery. There was a gradual augmentation in the withdrawal duration as was observed from the data from day 1 to day 7. No statistically significant difference was observed between recordings in sham group till day 7. Treatment with diazoxide at the dose of 200 mk/kg per orally for 7 days significantly reduced spontaneous pain in animals. Moreover a significant change in the mechanical and thermal evoked allodynia/hyperalgesia was also observed as compared to the CCI group. The development of thermal hyperalgesia and tactile allodynia is known to involve separate pathways (23). While noxious thermal stimuli is thought to be mediated through high-threshold, thin unmyelinated primary afferent C- fibers, non-noxious tactile stimulation is believed to be mediated through large diameter, low threshold Ab afferent fibers, and processed at supraspinal sites receiving input through the dorsal columns (24-26). We observed that there was retardation in the progression of the disease in drug treated group as compared to CCI group. But it was not restored to a normal value instead a partial restoration of values were obtained. More extensive research is needed in this area for more specific answers to the questions regarding the involvement of K+ channels in neuropathic pain.

CONCLUSION
Neuropathic pain is thought to become worse with time, untreated appropriately inducing a vicious circle. The development of agents that may block enhanced pain transmission is an important therapeutic approach for research. Neuropathic pains are resistant to conventional narcotic therapies and often incapacitate patients. The search for novel treatments for this pain syndrome characterized by central sensitization has stirred numerous investigations in both the basic science and clinical arenas. The present study indicates that activity of K+ channel may contributes significantly to the development of central sensitization-mediated pain and suggests that K+ openers may be an important molecular target for the treatment of chronic pain of neuropathic origin.

 

References:

1. Cruccu G, Anand P, Attal N, GarciaLarrea L, Haanp M, Jorum E et al. EFNS guidelines on neuropathic pain assessment. European Journal of Neurology 2004; 11 (3): 153–62

2. Woolf CJ, Ma Q. Nociceptors--noxious stimulus detectors. Neuron 2007; 55: 353-64.

3. Scholz J, Woolf CJ. Can we conquer pain? Nat Neurosci 2002; 5 Suppl: 1062-67.

4. Ueda H. Molecular mechanisms of neuropathic pain-phenotypic switch and initiation mechanisms. Pharmacol Ther 2006; 109: 57-77.

5. Hucho T, Levine JD. Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron 2007; 55: 365-76.

6. Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron 2006; 52: 77-92.

7. Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999; 353: 1959-64.

8. Matsumoto M, Inoue M, Hald A, Xie W, Ueda H. Inhibition of paclitaxelinduced A-fiber hypersensitization by gabapentin. J Pharmacol Exp Ther 2006; 318: 735-40.

9. Eisenberg E, Lurie Y, Braker C, Daoud D, Ishay A. Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study. Neurology 2001; 57: 505-9

10. Sakaue A, Honda M, Tanabe M, Ono H. Antinociceptive Effects of Sodium Channel-Blocking Agents on Acute Pain in Mice. J Pharmacol Sci 2004; 95: 181–88.

11. Wickenden AD, Roeloffs R, McNaughton-Smith G, Rigdon GC. KCNQ potassium channels: drug targets for the treatment of epilepsy and pain. Expert Opin. Ther. Patents 2004; 14(4): 1-13.

12. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988; 33: 87- 107.

13. Choi Y, Yoon YW, Na HS, Kim SH, Chung JM. Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain 1994; 59: 369–76.

14. Field M J, Scott M, Hughes J, Singh L. Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat. Pain 1999; 80: 391–98.

15. Decosterd I, Woolf CJ. Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 2000; 87: 149–58.

16. Field MJ, Bramwell S, Hughes J and Singh L. Detection of static and dynamic components of mechanical allodynia in rat models of neuropathic pain: are they signalled by distinct primary sensory neurones? Pain 1999; 83: 303–11.

17. Hunt SP, Mantyh PW. The molecular dynamics of pain control. Nat. Rev. Neurosci. 2001; 2(2): 83-91.

18. Kawano T, Zoga V, Mccallum JB, Wu HE, Gemes G, Liang MY et al. ATPsensitive potassium currents in rat primary afferent neurons: biophysical, pharmacological properties, and alterations by painful nerve injury. Neuroscience 2009; 162(2): 431-43.

19. Sachs D, Cunha FQ, Ferreira SH. Peripheral analgesic blockade of hypernociception: Activation of arginine/NO/cGMP/protein kinase G/ATP-sensitive K+ channel pathway. Proc Natl Acad Sci USA 2004; 101: 3680–85.

20. Sawynok J, Esser MJ, Reid AR. Peripheral antinociceptive actions of desipramine and fluoxetine in an inflammatory and neuropathic pain test in the rat. Pain 1999; 82: 149–58.

21. Tiraboschi E, Giambelli R, D'Urso G, Galietta A, Barbon A, de Bartolomeis A. Antidepressants activate CaMKII in neuron cell body by Thr286 phosphorylation. Neuroreport 2004; 15: 2393–96.

22. Attal N, Jazat F, Kayser V, Guilbaud G. Further evidence for „pain-related? behaviours in a model of unilateral peripheral mononeuropathy, Pain 1990; 41: 235–51.

23. Ossipov MH, Lai J, Malan Jr TP, Porreca F. Spinal and supraspinal mechanisms of neuropathic pain. Ann NY Acad Sci 2000; 909: 12–24.

24. Yeomans DC, Pirec V, Proudfit HK. Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: behavioral evidence. Pain 1996; 68: 133–40.

25. Ossipov MH, Bian D, Malan Jr TP, Lai J, Porreca F. Lack of involvement of capsaicin sensitive primary afferents in nerve-ligation injury induced tactile allodynia in rats. Pain 1999; 79: 127–33.

26. Willis WD, Al-Chaer ED, Quast MJ, Westlund KN. A visceral pain pathway in the dorsal column of the spinal cord. Proc Natl Acad Sci USA






Fig 1: Comparison of withdrawal duration (sec) in sham group and CCI group at the basal, day 1, 3, 5, and 7 days post surgery by sensory tests like (a) Spontaneous pain, (b) Dynamic allodynia, (c) Cold allodynia and (d) Mechanical hyperalgesia. Each data point represents the mean ± S.E.M. The significance of differences between the sham group and CCI group values was determined by unpaired t-test. *P<0.05 and **P<0.01, ***P<0.001 vs sham group in respective time.

Fig 2: Effect of Diazoxide (200mg/kg, p.o. once a day ) treatment for 7 days in CCI induced chronic pain at the basal, day 1, 3, 5, and 7 days by sensory tests like (a) Spontaneous pain, (b) Dynamic allodynia, (c) Cold allodynia and (d) Mechanical hyperalgesia. Each data point represents the mean ± S.E.M. The significance of differences between the drug treated group and CCI group values was determined by unpaired t-test. *P<0.05 and **P<0.01, ***P<0.001 vs sham group in respective time

Announcements

Dr. Pramod Kumar Manjhi joined Editor-in-Chief since July 2021 onwards

COPE guidelines for Reviewers

SCOPUS indexing: 2014, 2019 to 2021


Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

A study by Dorothy Ebere Adimora et al. entitled \"Remediation for Effects of Domestic Violence on Psychological well-being, Depression and Suicide among Women During COVID-19 Pandemic: A Cross-cultural Study of Nigeria and Spain\" is awarded Best Article of Vol 14 issue 23
A study by Muhas C. et al. entitled \"Study on Knowledge & Awareness About Pharmacovigilance Among Pharmacists in South India\" is awarded Best article for Vol 14 issue 22
A study by Saurabh Suvidha entitled \"A Case of Mucoid Degeneration of Uterine Fibroid with Hydrosalphinx and Ovarian Cyst\" is awarded Best article of Vol 14 issue 21
A study by Alice Alice entitled \"Strengthening of Human Milk Banking across South Asian Countries: A Next Step Forward\" is awarded Best article of Vol 14 issue 20
A study by Sathyanarayanan AR et al. entitled \"The on-task Attention of Individuals with Autism Spectrum Disorder-An Eye Tracker Study Using Auticare\" is awarded Best article of Vol 14 issue 19
A study by Gupta P. et al. entitled \"A Short Review on \"A Novel Approach in Fast Dissolving Film & their Evaluation Studies\" is awarded Best Article of Vol 14 issue 18.
A study by Shafaque M. et al. entitled \"A Case-Control Study Performed in Karachi on Inflammatory Markers by Ciprofloxacin and CoAmoxicillin in Patients with Chronic Suppurative Otitis Media\" is awarded Best Article of Vol 14 issue 17
A study by Ali Nawaz et al. entitled \"A Comparative Study of Tubeless versus Standard Percutaneous Nephrolithotomy (PCNL) \? A Randomized Controlled Study\" is awarded Best Article for Vol 14 issue 16.
A study by Singh R. et al. entitled \"A Prospective Study to Find the Association of Astigmatism in Patients of Vernal Keratoconjunctivitis (VKC) in a Tertiary Health Care Centre in India (Vindhya Region MP)\" is awarded Best Article for Vol 14 issue 15
A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


RSS feed

Indexed and Abstracted in


Antiplagiarism Policy: IJCRR strongly condemn and discourage practice of plagiarism. All received manuscripts have to pass through "Plagiarism Detection Software" test before Toto Macau forwarding for peer review. We consider "Plagiarism is a crime"

IJCRR Code of Conduct: To achieve a high standard of publication, we adopt Good Publishing Practices (updated in 2022) which are inspired by guidelines provided by Committee on Publication Ethics (COPE), Open Access Scholarly Publishers Association (OASPA) and International Committee of Medical Journal Editors (ICMJE)

Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.



ABOUT US

International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

Contact

148, IMSR Building, Ayurvedic Layout,
        Near NIT Complex, Sakkardara,
        Nagpur-24, Maharashtra State, India

editor@ijcrr.com

editor.ijcrr@gmail.com


Copyright © 2024 IJCRR. Specialized online journals by ubijournal .Website by Ubitech solutions