screening methods – analgesic drugs
TRANSCRIPT
Screening Methods – Analgesic Drugs
Dr. KEERTHI SAGAR J
• Pain : Unpleasant sensory and emotional experience associated with actual & potential tissue damage
• “an aversive sensory experience caused by actual or potential injury that elicits progressive motor and vegetative reactions, results in learned avoidance behaviour, andmay modify species specific behaviour, including social behaviour”.
Need for New Drugs
• In Vivo Studies• In Vitro Studies• Neuropathic Pain Models
Classification of Screening Methods
Classification of In Vivo Screening Methods
• Chemical Stimulation Methods
• Electrical Stimulation Methods
• Mechanical Stimulation Methods
• Thermal Stimulation Methods
• Writhing Test• Randal Selitto Test• Formalin Test
• Chemical Stimulation Methods
• Electrical Stimulation Methods
• Mechanical Stimulation Methods
• Thermal Stimulation Methods
• Electrical Stimulation of Tail
• Grid shock/ Flinch Jump Test
• Tooth Pulp stimulation in Rabbit
• Monkey Shock Titration Test
Classification of In Vivo Screening Methods
Classification of In Vivo Screening Methods
• Chemical Stimulation Methods
• Electrical Stimulation Methods
• Mechanical Stimulation Methods
• Thermal Stimulation Methods
• Haffner’s tail clip Test
Classification of In Vivo Screening Methods
• Chemical Stimulation Methods
• Electrical Stimulation Methods
• Mechanical Stimulation Methods
• Thermal Stimulation Methods
• Radiant Heat Method• Hot Plate Method• Tail Immersion Test
Chemical Stimulation Methods
Writhing Test
• Principle• Irritant – Phenylquinone
suspension 0.25ml• Response = Stretching
of abdomen + Stretching of one of the Hind Limb
Modifications
• 0.1ml of 0.65 acetic acid solution• In rats – 4% Sodium Chloride Solution
Randal Sellito Test
• Principle• Induction of
Inflammation: o.1ml of 20% Brewers Yeast suspension
Formalin Test
• 0.05ml 0f 10% Formalin into dorsal portion of front paw
• Observation= Favoring of paw• Protection= Both the paws are resting on the
floor
Electrical Stimulation Methods
Electrical Stimulation of Tail
• Stimulus: rectangular wave pulse, 40- 50 V, 1 Shock/s & Duration of Pulse is 2.5ms
Grid Shock Test/ Flinch Jump TestStimulus: 30 cycles per second square wave pulses with the duration of 2ms per pulse
Rabbit Pulp Stimulation• Anesthesia - Thiopental
15mg/kg/ fentanyl 0.2mg/kg
• Stimulus : rectangular current of 50Hz, duration of 1s. Starting current 0.2mA & ↑ at the interval of 0.1mA
• Response= licking, biting, chewing & head flick
• Threshold Current?
Monkey Shock Titration Test
Mechanical Stimulation Methods
Haffner’s Tail Clip Method
• Response= Biting of the clip/ The tail near the location of Clip
• Cut off time= ARTControl + 3SD
• Positive Response= > Cut Off Time
Thermal stimulation Methods
Radiant Heat Method
• Response1. Escape Reaction2. Spinal Reflex• Cut off time = 6s
Hot Plate Method
• Principle• Response= Licking The
Paw/ Jumping• t- Test
Tail Immersion Test
• Cut off time of Immersion= 15s• Normal = 1-5.5s• Positive= >6s
5 most common tests in medline used to test nociception
Neuropathic Pain
• Chronic Nerve Constriction Injury• DS= PWL Control- PWL Test
In Vitro Methods
• 3H-Naloxone Binding Assay• 3H-Dihydromorphine Binding to μ Opiate
Receptors in Rat Brain• 3H-Bremazocine Binding to κ Opiate
Receptors in Guinea Pig Cerebellum