# Lab 3#. Introduction - Pain: an unpleasant sensory and emotional experience associated with actual...
-
Upload
jesse-gregory -
Category
Documents
-
view
219 -
download
1
Transcript of # Lab 3#. Introduction - Pain: an unpleasant sensory and emotional experience associated with actual...
Introduction- Pain: an unpleasant sensory and emotional
experience associated with actual or potential tissue damage, or described in terms of such damage
- Analgesics : Drugs used to relief or suppress the pain.
pain is associated with electrical activity in small diameter primary afferent fibers of peripheral nerves .
These nerves have sensory ending in the peripheral tissues and activated by noxious stimuli of various kinds :
I. Chemical stimuliII. Thermal stimuli III. Mechanical stimuli
Types of afferent sensory nerve fibers :
C- fibers A - fibers
Non- myelinated Myelinated
Low conducting velocity
High conduction velocity
Cause a dull burning and non-
localized pain
Cause a sharp and localized pain
NociceptorsA Sensory receptor that sends signals that
cause the perception of pain in response to a potentially damaging stimulus.
These receptors are activated by mechanical, thermal and chemical stimulants.
Provide information about the location, intensity and duration of a noxious stimulus to the body
Nociceptors are connected to primary afferent nerve fibers.
Pain Mediators
pain mediators include : bradykinin, leukotriene, substance P,
histamine, Ach, 5-HT and prostaglandins
they increase the sensitivity of the nerve ending to other pain mediators
Pain Mediators Mechanism of action of the paim mediators to
cause pain :
I. Direct : stimulate of the nerve ending directly via nocieceptors.
II. Indirect : increase the sensitivity of nerve ending to other pain mediators.
Analgesics are divided into
Narcortic analgesics( opioid analgesics )
e.g. Morphine
Non- narcotic analgesics (non- opioid analgesics)
(non- steroidal anti-inflammatory drugs)
NSAIDs
e.g. Aspirin
Opioid analgesicsOpioid include natural (Morphine),
semisynthetic (Heroin) and synthetic (Fentanyl).
They reduce moderate to severe pain without loss of consciousness.
They act by binding to specific receptors located primarily in the brain and spinal cord.
Opioid analgesicsThe major classes of opioid receptors are(
μ, κ, δ) mu, delta and kappa.
Each receptor type has subtypes: mu1, mu2, delta1, delta2, kappa1, kappa2 and kappa3.
Most of the currently available opioid analgesics act primarily at the mu receptor.
Mechansim of action :
All opioid recptors are linked through G-proiten by inhibition of adenylate cyclase i.e facilitate opening of K channels ( causing hyperpolarization ) and inhibit opening of Ca channels ( inhibiting transmitters release )
They stimulate the release of endogenous opiod peptide ( endorphins and enkephalins) which cause decresing in release of pain mediators.
Side effects:
Dependency and tolerance
Nausea and constipation
CNS: drowsiness, lightheadedness, euphoria or dysphoria, or
confusion.
Urinary retention
Respiratory depression, particularly in elderly or debilitated
patients
Miosis ( constriction of the pupil )
Non opioid analgesics (NSAIDs) Aspirin and other NSAIDs are useful for the
treatment of pain from injury ( mild to moderate )
Examples for NSAIDs :
I. Cox ( cyclooxygenase) non selective : Aspirin,
Ibuprofen, Diclofenac …etc
II. Cox2 selective : Celecoxib and Rofecoxib.
Phospholipids
Phospholipase A2
Arachidonic Acid
Prostaglandins Thromboxanes
Prostacyclin
COX
Leukotrienes
Lipoxygenase
LAB WORKObjective :
To show the analgesic effects of different analgesics using different methods.
I. Writhing test.II. Hot plate method.
Writhing test
Principle:
Pain is induced by injection of noxious
chemical as Acetic acid 0.1% at volume 0.3
ml.
Writhing means stretching behavior of the
abdominal and at least one hind limb.
Procedure:
1.First inject the mouse with acetic acid and
calculate the number of writhing/20 minutes
and this will be control test.
2.Inject the second animal with aspirin and
inject the third one with morphine.
3.After 5 minutes inject the animals with
acetic acid then calculate the number of
writhing/20 minutes.
Procedure:
4.Compare the number of writhing for each
drug and comment on the results (a drug
has more number of writhing >>> more
potency as analgesic.
DrugNo. of
writhing/20 minutes
Control Acetic cid
Test 1Morphine acetic
acid
Test 2 Aspirin acetic
acid
5 min’s
5 min’s
Hot plate methodprinciple:
The paws of the mouse are very sensitive to heat
at temperature which are not damaging the skin .
At temperature of 55 C the mouse will jump and
licking the paws.
The time till these response occur is calculated
and is prolonged after administration of analgesics.
Procedure:
1. Put the mouse on the hot plate and record the time
taken in order to jump or licking the fore paws.
2. Record the time in seconds this is the control time.
3. Weight the animal and calculate the dose of
Morphine and Aspirin
4. At 5 min’s interval ( for 30 min’s ) place the animal
on the hot plate and record the time to see the
response .
5. Compare the time need to see the response the drug
with longer time is more potent as analgesic.