Rat paw lick model

Gupta, P.K., Patel, J.P., and Hahn, K.R., Evaluation of pain and irritation following local administration of parenteral formulations using the rat paw lick model, /. Pharm. Sci. Technol., 48, 159, 1994. 

Results from the rat paw lick model seem to correlate well with clinical painfulness experience and the muscle irritation test with certain antibiotic formula-tions. However, because rat paw lick results from a wide variety of drug formulations have not been published, these correlations may hold only for a certain subset of painful formulations. A formulation could cause pain but yet not cause muscle damage upon intramuscular injection. Additionally, some formulations are painful upon intravenous injection. 

Pain on injection is usually of greatest concern with intramuscular injections because of the long residence time of the formulation at the injection site. Not surprisingly, there are no in vitro models to test the potential of a formulation to cause pain It is therefore necessary to test for the potential to cause pain by means of an in-vivo model. Gupta et al. (1994b) describe the use of the rat paw lick model for the assessment of pain in response to formulation pH and co-solvent concentration. The potential for muscle damage should also be evaluated when developing an intramuscular formulation, and the industry standard is the rabbit lesion volume model (Sutton et al. 1996). 

Models that do assess pain on injection are the rat paw lick and mouse scratch models. In the paw lick model, the drug formulation is injected into the pad of the hindfoot, and the number of times the rat licks the paw is counted. The mouse scratch test is similar except that the formulation is injected subcutaneously on the back, and the number of times the mouse scratches the injection site is counted. 

A model of thermal pain. Mice or rats are placed on a heated metal plate of variable temperature. Depending on the temperature (48-58 °C), a weak or strong pain stimulus is induced. Animals respond either by licking their paws or by jumping. Analgesics increase the latency for this pain reaction. The low temperature hot plate detects a broader spectrum of less efficacious analgesics in comparison to its high temperature modification or the tail flick test (Eddy and Leimbach J. Pharmacol. 1953, 107, 385). 

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