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Updated: Sep 26, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
The algogenic-induced nociceptive flexion test in mice: studies on sensitivity of the test and stress on animals
Makoto Inoue1, Md Harunor Rashid, Toshiko Kawashima
1Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Abstract:
Recently we developed a new technique, known as peripheral nociception test or algogenic-induced nociceptive flexion (ANF) test, to study the in vivo signal transduction of pain at the peripheral nerve endings in mice. In the present report, we examined the sensitivity of the method to detect pain signal and the stresses induced by the test on experimental animals. In the algogenic-induced biting and licking (ABL) test, bradykinin could not induce significant biting-licking response even at a dose of 1nmol. It induced significant biting-licking response only at 10nmol. However, with the ANF test, 100fmol of bradykinin was enough to produce sharp and significant nociceptive flexion response. Similarly, substance P, ATP and ONO-54918-07, a stable prostaglandin I(2) agonist, induced nociceptive flexion response in ANF test at much lower doses than needed to induce biting-licking responses in ABL test. Next, we measured the plasma corticosterone level after different nociception tests, which is a measure of stress on animals due to experimental manipulations. However, no significant rise in corticosterone level was observed with ANF test. Altogether, these findings indicate that the ANF test is a highly sensitive and less stressful technique to study in vivo mechanisms of pain at the peripheral nerve ending.

