3.5.3 Pharmacology I
Lab 11 Evaluation of analgesic action of Tramadol on rats using hot plate analgesiometer
Theory (Cont'd...): Tissue irritation or injury causes the release of some mediators like prostaglandins,
leukotrienes, serotonin, platelet activating factor, kinins that stimulate the nociceptors and causes the pain, called
peripheral pain. The relief from such type of pain can be obtained either by inhibiting the propagation of nerve impulse or
by using a molecule, capable of inhibiting the action of such mediators (eg. non steroidal anti inflammatory agents,
glucocorticoids). Temperature, bellow 100 C or above 480 C also stimulate the pain receptors, instead of stimulating the
thermoreceptors (stimulated in the temperature range of 100 C to 480 C) and produce the painful sensation. There are few
physiological analgesic like endorphin, enkephalin, dinorphin and serotonin (less potent), those bind with the opioid
receptor and inhibit the propagation of nerve impulse in the CNS. Binding with opioid receptor causes the opening of
K+ channels and closing of Ca++ channels (inhibiting the release of substance P) followed by the hyperpolarisation of the
post synaptic neurons. This causes the inhibition of nerve impulse propagation. Thus, the analgesic action is obtained.
Opioid receptor agonists (eg. morphin, codeine, pethidine) can act as a central analgesic by the same mechanism as endorphin
or enkephalin. Tramadol acts as a central analgesic by binding with the $\mu$ opioid receptor (low affinity) as well as by
inhibiting the reuptake of serotonin and noradrenalin in the CNS. Tramadol blocks the impulse at the spinal level.
Materials: Sprague-Dawley rats, weighing 320~450 g, hot plate analgesiometer, timer, narcotic analgesic
(Tramadol HCl: 10 mg/kg B. W.), NS (as control), Needle.
Method: Analgesic effect in rats was assessed by hot plate model analgesiometer by the method of
Baker et al., 2002 with few modifications. A metal hot-plate was heated to a constant temperature of 50±50 C. The temperature
of the plate was monitored at all times. The latency of licking of paw for each animal of the group is noted before the
administration of the drug and up to 3 hours, after the administration of the drug (10 mg/Kg B.W., i.p.) in 1 hour interval.
After each measurement the plate was wiped with a damp cloth to remove traces of urine and faeces.
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