This document provides an overview of analgesic models used to study pain and the effects of pain medications. It begins with definitions of pain, nociception, and classifications of acute and chronic pain. It then discusses various types of analgesics and how they are classified. The remainder of the document outlines several experimental animal models used to test analgesics, including thermal, mechanical, electrical, and chemical stimulus models. It also discusses in vitro assays and models of chronic pain conditions. In conclusion, the document provides an in-depth review of the major experimental models employed in analgesic research using animal subjects.
This power point presentation include the definition of the peptic ulcer, formation of peptic ulcer, regulation of gastric acid secreation, sign and symptomes, etiology of chronic ulceration, acid- pepsin vs mucosal resistance, gastric hyper secreation, disease complication, infection and obstruction, different factors related to acid secreation, classification of drugs used in peptic ulcer animal models in experimental peptic ulcer in both in-vivo and in- vitro
In this slide contains diabetics, classification, symptoms, complication, invivo and invitro screening models of anti diabetics.
Presented by: GEETHANJALI ADAPALA (Department of pharmacology).
RIPER, anantapur
This seminar is my attempt to discuss screening of anti-emetic drugs using different animal models. The materials used in the presentation is derived from different standard textbooks, internet and journals. Please feel free to suggest ways to improve it.
This power point presentation include the definition of the peptic ulcer, formation of peptic ulcer, regulation of gastric acid secreation, sign and symptomes, etiology of chronic ulceration, acid- pepsin vs mucosal resistance, gastric hyper secreation, disease complication, infection and obstruction, different factors related to acid secreation, classification of drugs used in peptic ulcer animal models in experimental peptic ulcer in both in-vivo and in- vitro
In this slide contains diabetics, classification, symptoms, complication, invivo and invitro screening models of anti diabetics.
Presented by: GEETHANJALI ADAPALA (Department of pharmacology).
RIPER, anantapur
This seminar is my attempt to discuss screening of anti-emetic drugs using different animal models. The materials used in the presentation is derived from different standard textbooks, internet and journals. Please feel free to suggest ways to improve it.
Non-steroidal anti-inflammatory drugs, also known as NSAIDs are medicines that are used to relieve pain, and reduce swelling (inflammation). Examples include aspirin, naproxen, ibuprofen, diclofenac, and COX-2 inhibitors such as celecoxib and meloxicam.
Anlalgesic activity and its classificationKOMAL AROOSH
Analgesics are medicines that are used to relieve pain. They are also known as painkillers or pain relievers. Technically, the term analgesic refers to a medication that provides relief from pain without putting you to sleep or making you lose consciousness.
Analgesics are drugs used to relieve pain. In this presentation, the various in vitro and in vivo screening methods for the preclinical testing of analgesics are discussed.
Screening methods of immunomodulators by shivam diwakerShivam Diwaker
Immune Modulators are the substances or drugs or chemical compounds that are used for the modification in the Immune system such as stimulate and suppress.
A large percentage of plants used in Ayurvedic practices and herbal medicines are subjected to controversy. Controversial drugs or Sandigdha Dravyas is term used for medicinal plants having controversial botanical sources due to polynomial nomenclature system of Sanskrit, non availability of plants and parallel evolved knowledge.
Adulterants and Substitutes are the common practices in herbal raw material trade. Adulteration is a debasement of article intentionally for commercial purpose or accidentally due to lack of knowledge of identification and proper collection.
Substitution is a replacement of equivalent drugs in place of original drugs on the basis of similar Rasa, Guna, Veerya, Vipak and mostly on Karma.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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6. Definition of Pain
An unpleasant sensory or emotional
experience associated with actual or
potential tissue damage, or described
in terms of such damage. (IASP)
8. Concept of Pain in Ayurveda
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9. Types of Human Pain
Various types of pain are seen in humans: eg.
– Somatic pain (arising from the skin, Muscles,
joints, ligaments and bones)
– Visceral pain
– Referred pain
– Neuropathic pain
– Cancer pain etc.
10. Classification of Pain
Acute Pain:
• Source is soft tissue damage, infection or
inflammation
• Short duration
• “Symptom of pain”
11. Chronic pain:
• Lasts for six months or longer,
• “The disease of pain”
• Common causes are cancer, neuropathic and
arthritic.
12. ANALGESICS
• The drugs which possess significant pain
relieving properties by acting in the central
nervous system , or on the peripheral pain
receptors without significantly affecting
consciousness.
13. Classification of analgesics:
NARCOTIC ANALGESICS NON NARCOTIC ANALGESICS:
Act centrally Act peripherally
Cause addiction Do not cause addiction
Produce CNS depression Do not produce CNS depression
Do not produce gastric
irritation
Produce gastric irritation
Show no anti inflammatory
effect
Show anti inflammatory effect
eg. Morphine, Tramadol,
Pethidine etc.
Diclofenac, Ibuprofen, Aspirin
etc.
15. ANALGESIC MODELS
• The animal models employed for screening of
analgesic agents are analgesic models.
• For animal models of pain, the word “model”
refers to three entirely separate entities-
– subject,
– assay and
– measure.
16. EXPERIMENTAL MODELS:
1. Models using thermal stimuli:
– The tail flick model using radiant heat/immersion of the
tail in hot water
– Pain withdrawal test
– Hot plate test
– Pain state models using cold stimuli
• Cold tail flick test
• Cold ethanol tail flick test (CET)
2. Models using mechanical stimuli:
– Haffner’s tail clip method
– Randall Selitto Test
– Strain gauges
– Von Frey filaments
– Inclined plane test
17. 3. Models using electrical stimuli:
– Electrical stimulation of the tail
– Grid shock test
– Stimulation of the tooth pulp
– Monkey shock titration test
– Stimulation of the limbs.
4. Models using chemical stimuli:
– Formalin test
– Acetic acid induced writhing test
– Stimulation of hollow organs
• Rat sigmoid colon model
• Inflammatory uterine pain model
18. MODELS FOR CHRONIC PAIN
• Neuropathic pain models
• Vincristine induced neuropathy model
• Diabetic neuropathy model
• Persistent post thoracotomy pain model
• Rat model of incisional pain
• Rat model of bone cancer pain
19. IN VITRO METHODS
• H – Naloxone binding Assay
• Micro opiate receptor binding assay
• Assay to study cannabinoids activity
• Receptor binding of nociception
• Bioassays for nociception
• Vanilloid receptor binding
21. A. PAIN STATE MODELS USING
THERMAL STIMULI
1. The Tail Flick models:
• Commonly accepted model for
quantifying analgesic response in
animals.
• In this model, radiant heat is applied to
a small surface of the tail or the tail is
immersed in hot water.
22. a. Tail flick model using radiant heat:
• Hardy et al. 1940 used on human
• Then used in Rat (1953)
• The tail flick test with radiant heat is a
simplified method the application of
thermal radiation to the tail of an animal
provokes the withdrawal of the tail
• The morphine like drugs are capable of
prolonging the reaction time.
24. Procedure
–The tail of Wistar rat (170-
210gms) is placed on the
radiant source and time
taken for the rat to withdraw
its tail is recorded.
Withdrawal of the tail from
heat source is referred to as ‘
tail flick latency’. Exposure of
the tail with radiant heat is
done for 10-20 seconds.
25. Evaluation:
• The tail flick latency in the test, standard, and
control animals are compared
• A lengthening of the reaction time is
interpreted as an analgesic action.
• Using various doses, ED-50 values can be
calculated.
26. Merits
• Effective for screening Morphine like
analgesics
• Simple technique, which does not
require any special skill
• Results of experiments are quite
accurate and less time consuming.
27. Demerits:
• Tail flick response is prone to habituation
• Efficient only for revealing the activity of
opioid analgesics
• Prolonging exposure to radiant heat
beyond 20 seconds may cause burning of
tail.
28. Modification
• USG induced tail flick procedure
• Ear withdrawal by applying radiant
heat
• Tail flick formalin test in rodents:
changes in skin temperature
29. b. Tail flick model using immersion of the tail:
• Distal 5 cm of the tail of wistar rat
is marked and immersed in a cup
of warm water ( 55°Cto56°C) for
15 seconds.
• The reaction time is determined
periodically after administration
of test drug (0.5, 1, 2, 3, 4, and 6
hours)
30. Tail flick model using immersion of
the tail
Mouse Tail-Flick, Allegheny College.mp4
31. • Response and Evaluation: - Withdrawal of tail or
attempt to escape or abrupt movement of tail
and sometimes the recoiling of whole body is
seen.
• Centrally acting analgesics are capable of
causing prolongation of tail withdrawal
reflex( more than 6 sec.).
• Modification:
–Cold tail Flick test
–Cold ethanol Tail flick test
32. 2. Hot Plate Model
• Introduced by Woolfe and
Mc Donald in 1944
• Mice are put on the
hotplate(temp. 55° to56
°C)and then latency is
noted following
administration of test drug.
• Response – jumping or paw
licking.
34. EVALUATION
• The prolongation of latency time between the
test, standard and control animals are
compared (by using t-test)
• Using various doses ED-50 values can be
calculated.
35. B: PAIN STATE MODELS USING
MECHANICAL STIMULI:
1. Haffner’s Tail Clip Method:
• Preferred sites for applying nociceptive
mechanical stimuli are the hind paw and the tail
• Highly sensitive for centrally acting drugs
• Tests using constant pressure have been
abandoned progressively for those applying
gradually increasing pressures
36. PROCEDURE
• An artery clip is placed at the root of tail of mice.
• A quick response is seen as biting the clip or tail,
where clip has been placed. The reaction time is
noted by a stopwatch.
• The test compounds are administered
subcutaneously or orally.
• Then after 15, 30, and 60 minutes, the same
procedure is repeated and the reaction time is
measured.
37. EVALUATION
• Reaction time of the test animals, greater
than the cut off time denotes a positive
response, indicating analgesic activity.
38. PAIN STATE MODELS USING
ELECTRICAL STIMULI: Grid shock
method
-Blake et al (1963)
-Used for central and peripheral analgesics
-Stimulus is given in the form of square wave pulses
to male mice . The output of the stimulator is
connected to the wires of grid with fixed
resistance which is kept parallel to oscilloscope
-Pain thresholds are determined in each individual
mouse twice before and after administration of the
test drug.
-Response- on oscilloscope , a starling reaction ,
increase locomotion or attempt to jump.
39. EVALUATION
• Current in milli-ampere is
recorded in each mouse before
and after administration of drug
is noted.
• The average pain threshold
values for each group at each
time interval are calculated and
statistically compared with the
control values.
40. D. PAIN STATE MODELS USING
CHEMICAL STIMULI
• Slow, progressive, and
irreversible form of
stimulation
• Closest in nature to
clinical pain
41. 1. Formalin Test
• 10% formalin solution is used as noxious stimulus
which is injected into the paw of rat or mouse and
inflammation is created as a model of persistent
or chronic pain.
• Two phases reactions are shown – Early phase
starts immediately after injection, and lasts for 3-5
minutes
• The second phase starts after 10—15 mins. of
injection and lasts for 20-40 mins.
• Opioid analgesics are effective in both phases,
while NSAIDs are effective in the second phase.
42. • Male wistar rats ( 180-300gms) are administered
subcutaneously with 0.05 ml of 10% formalin in
dorsum of the front paw.
• Each animal is placed into separate cages for
observation of pain responses in early and late
phases.
• Responses are as elevation or favoring of paw, or
excessive licking and biting of the paw
PROCEDURE
43. • Scoring is done according to the pain scale
• Then test drug is administered and again scoring is
done after 30, 60, minutes for comparison
• If both paws of animal are allowed to rest on the
floor with no obvious favouring of the injected paw,
this is taken as positive analgesic response.
Contd..
44. b. Writhing Test
• Model of visceral or peritoneal
pain in animals
• Test is issued to detect
peripheral analgesic activity
• Pain is induced by intra
peritoneal administration of
chemicals, which irritate serous
membrane and provoke a
stereotype behaviour in the
mouse or rat known as writhing.
• Chemicals used are acetic acid,
acetylcholine, bradykinin,
aconitine, 4% NaCL, etc.
45. PROCEDURE
• Acetic acid solution is
administered to the mice(20-
25gm.) and placed individually
in the glass jar.
• The test and standard drug is
administered 15 minutes prior
to the acetic acid administered.
• Responses are noted.
47. EVALUATION
• The writhing period is recorded for 10 minutes
and compared with the control group.
• Writhing response in the drug treated must be
less when compared to the acetic acid treated
control.
48. IN VITRO MODELS
BIOASSAYS FOR NOCICEPTION
Purpose and rationale:
Nociception receptors in the periphery can be
characterized by studies in isolated
organs(Guerrini et al.1998,Bigoni et al.1999) .
The guinea pig ileum , according to Paten 1957,
the mouse vas deferens according Hughes etal.
1975, the rabbit vas deferens according to Oka
et al. 1980, the guinea pig renal pelvis according
to Giuliani and magi 1996.
49. PROCEDURE
• Tissues are taken from male Swiss mice, guinea
pigs, Sprague Dawley rats, and New Zealand
albino rabbits.
• Suspended in 10 ml organ baths containing
Krebs solution oxygenated with 95% oxygen
and 5% carbon-dioxide.
• Temperature is set around 33-35 degrees and a
resting tension of 0.3-1 gm is applied
• The tissues are stimulated through two
platinum ring electrodes
50. • The electrically evoked contractions are
measured isotonically with a strain gauge
transducer and recorded on a multichannel chart
recorder.
• After equilibration period about 60 mins, the
contractions induced by electrical field
stimulation are stable. At this time, cumulative
concentration response curves to nociception or
opioid peptides are performed.
Contd..
51. • Four electrical field stimulation are performed
with each tissue at 30 min intervals.
• Agonists and antagonists are added to the
bath
• Contractile response to electrical field
stimulation are expressed as % increment to
the spontaneous activity of the tissue.
• The biological effects of the application of
agonists or antagonists are expressed as %
inhibition of electrical field stimulation
induced contraction.
Contd..
53. MODELS OF CHRONIC PAIN:
• Rat Model of Incisional Pain:
• This model helps to understand mechanisms of
sensitization caused by surgery and investigate new
therapies for post operative pain
• A longitudinal incision of 1 cm is given through the skin,
fascia and muscle of the plantar surface of the hind
paw in halothane anesthetized rats.
• Withdrawal responses are measured using Von Frey
filaments at different areas around the wound before
surgery and for the next 6 days.
• The results of tests for withdrawal responses suggest
that surgical incision of the rat foot causes mechanical
hyper-algesia lasting for several days after surgery.
54. RESEARCH ARTICLES
• The necessity of animal models in pain research
• Jeffrey S. Mogil a,*, Karen D. Davis b,c, Stuart W. Derbyshire
• IASP PAIN 151 (2010) 12–17
• Abstract-There exists currently a fair degree of introspection in
the pain research community about the value of animal research.
This review represents a defense of animal research in pain. We
discuss the inherent advantage of animal models over human
research as well as the crucial complementary roles animal
studies play vis-à-vis human imaging and genetic studies. Finally,
we discuss recent developments in animal models of pain that
should improve the relevance and translatability of findings using
laboratory animals. We believe that pain research using animal
models is a continuing necessity–to understand fundamental
mechanisms, identify new analgesic targets, and inform, guide
and follow up human studies–if novel analgesics are to be
developed for the treatment of chronic pain.
55. Animal models of pain : progress and challenges
Jeffrey S. Mogil
Nature Review, Neuroscience; Vol. 10, April 2009;
pg 283-94
Abstract:
Many are frustrated with the lack of translational progress in the pain field, in
which
huge gains in basic science knowledge obtained using animal models have not
led to the development of many new clinically effective compounds. A
careful re-examination of animal models of pain is therefore warranted.
Pain researchers now have at their disposal a much wider range of mutant
animals to study, assays that more closely resemble clinical pain states, and
dependent measures beyond simple reflexive withdrawal. However, the
complexity of the phenomenon of pain has made it difficult to assess the true
value of these advances. In addition, pain studies are importantly affected by a
wide range of modulatory factors, including sex, genotype and social
communication, all of which must be taken into account when using an animal
model.
56. Evaluation of the Analgesic and Anti inflammatory
Activity of Kadamba (Anthocephalus cadamba miq.) –
an experimental study
Thesis dissertation by Dr. Prakash L Hegde, submitted to
the RGUHS
• Used model – Hot Plate Method
• Conclusion - Alcoholic extract of Kadamba has potent
analgesic and anti-inflammatory activity almost like
standard drug.
• Thus kadamba is a freely available safe drug showing
efficacy in single use both in extract and kashaya form on
rats. Same has to be reconfirmed on human beings.
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How the Vaidya examines and certifies
the King’s food:
First, he should test it by fire, then, by
feeding it to a peacock to determine whether
it is poisonous or not. Then, he should chant
holy hymns and chants to ward of evil, and
should ensure that the king has donned and
sacred stones and medicaments as
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There are four stages in the case of quadrupeds, and
three stages in that of birds. In the animal, in the first
stage, there will be asthenia and whirling; in the
second stage the animal quivers, and in the third,
passes into stupor and takes no food. In the fourth
stage respiration becomes hard and it dies. The bird in
the first stage of poisoning feels depression and in the
second stage whirling in the third stage its limbs get
paralysed and death ensues.
60. DISCUSSION
• Pain –
– Common unpleasant sensory and emotional
experiences.
– Acute, chronic, somatic, visceral, Neuropathic etc are
different ways of experiences of pain.
– In Ayurveda pain is described as Vedana, Ruja, Shoola,
Angamarda, Arti etc.
– Nociception – Pain due to noxisious stimuli
61. • Analgesics –
– Various types
– New drugs are introducing continuously due to
limitations and adverse effects of existing one.
– Bright future for Ayurvedic drugs in field of Analgesics
– Ayurveda system seeking potent analgesic drugs for
different types of pain
• Ayurveda and Analgesic
– Acharyas mentioned different drugs in Vedana-
Sthapaka, Shoolprashaman, Angamardaprashaman
Gana.
– These drugs should be tested by analgesic models and
Contd..
63. • Analgesic models
– Analgesic models are equally applicable for phasic or
acute pain as well as tonic or chronic pain.
– Centrally acting and peripherally acting analgesics. both
can be evaluated by analgesic models.
– Different thermal, mechanical electrical and chemical
stimuli are used.
– In-vitro models are also used.
64.
65. – Haffner’s tail clip method, hot plate method, tail
immersion method, grid shock test, formalin test in rats
etc. are used mainly for central analgesic activity.
– Responses given by the subject of the analgesic models
helps to determine analgesic effect.
– Writhing test, Randall Selitto test, mechanical/visceral
pain models in the rat etc. Are used mainly for
peripheral analgesic activity.
– Animal models are necessary for pain research, having
various challenges.
– In Ayurveda, birds and other animals were used as
experimental model in few extent.
Contd..
66. CONCLUSION
• Analgesics have to be tested not only for their in
vitro activity, but also for their in vivo analgesic
potential
• The most commonly used methods for
measuring peripheral analgesics activity are the
writhing test in mice.
• Tail flick method, Hot plate method and
Haffner’s tail clip method are common methods
for measuring central acting analgesic effects.
67. • Herbs described as vedanastahpaka, vedanahara,
shothahara,
shoolprashaman,Angamardaprashaman could be
tested for their respective analgesic effects by
using analgesic models.
• Limitations of different models should be tackled
with modification in subject, assays and
measures.
68. References
• Charak Samhita
• Astanga Sangraha
• K. D. Tripathi. Essential of Medical Pharmacology
• Drug Screening Methods : SK Gupta
• Dr. Prakash L. Hegde; Evaluation of the Analgesic and Antiinflammatory Activity
of Kadamba (Anthocephalus codamba Miq.): An Experimental Study
• DANIEL LE BARS,MANUELAGOZRIU, AND SAMUELW.CADDEN-Animal Models of
Nociception,The American society for pharmacology and experimental
therapeutics : vol 53 no.4 ; 597- 612
• Parle Milind, Yadav Monu. Laboratory Models for Screening Analgesics.
International research Journal of Pharmacy. 2013;4 (1): p-15-19
• Jeffery, S. Mogil, Karen D. Davis, Sturt W. Derbyshire The necessity of animal
models in pain research – comprehensive review, PAIN 151 (2010); p.12-17
• Jeffery, S. Mogil – Animal models of pain: progress and challenges, Nature
Reviews / Neuroscience; 2009 April: (10); p-283-294