Algesia- Derived from the Greek word algesis (sensitivity to pain).
Hyperalgesia- An extreme sensitivity.
Analgesic - Derived from Greek word an (without) and algos (pain) means absence of pain.
Pain
An unpleasant sensory and emotional experience with actual or potential tissue damage.
Types of pain-
Somatic pain (arising from the skin, muscles, joints, ligaments and bones), visceral pain, neuropathic pain , cancer pain.There are various chemical mediators for the pain such as 5-HT , substance P and mediators extrinsic to nervous system including prostaglandins, kin ins, cytokines, chemo-kines etc. Pain is produced by the excitation of particular receptors , nociceptors of their afferent fibers. Most of the afferent fibers that are excited by noxious stimuli are non-myelinated C-fibers with low conduction velocity.
Classification of Analgesic
Opioids Analgesic:
These are morphine derivatives.
Example- morphine, codeine, heroin, fentanyl.
Uses- moderate to severe pain.
Non-Opioids Analgesic-
Non-steroidal anti –inflammatory drugs.
Example- aspirin , ibuprofen , paracetamol
Uses- mild pain , anti-inflammatory.
Screening Methods of Analgesic Activity
1) Chemical method
A) Writhing test
B) Randall-selitto test
C) Intra-arterial bradykinin test
D) Formalin test
2) Electrical simulation method
A) Electrical stimulation of tail
B) Flinch- jump test in mice
C) Tooth pulp stimulation in rabbits
3) Mechanical Stimulation Method
A) Haffner’s tail-clip test in mice
4) Thermal Stimulation Method
A) Radiant-heat(tail-flick) method
B) Tail immersion method
C) Hot plate method
Model Used For Central Analgesic Activity
A) Haffner’s tail clip method in mice.
B) Tail flick / others radiant heat method.
C) Tail immersion tests.
D) Hot plate method.
E) Electrical stimulation method.
F) Monkey shock titration.
G) Formalin test.
Model Used For Peripheral Analgesic Activity
A) Writhing test.
B) Randall-selitto test.
1) Radiant Heat Method OR Tail Flick Test
Purpose And Rational
This method was developed by schumacher & walff (1940) for quantitative measurement of pain threshold in man against thermal radiation. Also for evaluation of analgesic activity of opioids. This test is very useful in discriminating b/w centrally acting analgesic and non-opioids analgesic. Widely and reliably used test for revealing the potency of opioid analgesics.In this heat is used as noxious stimulus.
The stimulus causes a simple nociceptive spinal reflex response in which the rat or mouse flicks its tail away from the heat source.
Tail Flick Test Procedure:
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| Flow Diagram Radiant Heat Method OR Tail Flick Test |
2) Hot Plate Method
Widely used to evaluate opioids analgesics. Paws of rodents are highly sensitive to heat at temperature which do not damage their skin. In this jumping , withdrawing of paws & licking of paws are recorded. Opioids prolonged the time required for the onset of these responses while peripheral or nsaids do not affect this responses. Helpful in the differentiation of opioids and NSAIDS.
Hot Plate Test Procedure :
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| Flow Diagram of Hot Plate Test Procedure |
Hot Plate Analgesiometer:
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| Hot Plate Analgesiometer |
3) Tail Immersion Test
Widely and reliably used test for revealing the potency of the opioids. The procedure is based on the observation that the opioids are selectively capable of prolonging the rxn time of the typical tail-withdrawal reflex in rat induced by immersing the end of the tail in warm water of 55°C.
Tail Immersion Test Procedure:
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| Flow Diagram Tail Immersion Test |
Chemical Methods
1) Writhing test
Model for the visceral or peritoneal pain. Used to detect peripheral analgesic activity of a test compound. In this pain is induce by intra-peritoneal administrative of chemical that irritates serous membrane & provoke a stereotyped behavior known as writhing.
Purpose And Rational:
- Suitable to detect analgesic activity.
- Pain is induced by injection of irritants into the peritoneal cavity of mice & animal show a characteristic stretching behavior (writhing).
Evaluation:
- Four drug group and a vehicle control group are employed.
- ED50 is calculated.
Writhing test Procedure :
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| Flow Diagram Writhing Test |
Writhing Test Calculating Formula:
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| Writhing Test Calculating Formula |
Other chemical which are producing writhing behavior -
Examples- Glacial acetic acid, Bradykinin, prostaglandin E1 , Ethacrynic acid, Aconitine, 4% Nacl.
2) Formalin Test
Formalin Test Procedure:
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| Flow Diagram Formalin Test Procedure |
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