Intradermal hypertonic saline-induced behavior as a nociceptive test in mice

We report a nociceptive test involving peripheral irritation which produces behavior similar to that elicited by intrathecally injected substance P. Intradermal hypertonic saline injected to the lower abdominal area produced quantifiable behavior in mice. The behavior consisted of licking, biting and scratching directed to the location of i.d. injection, and was dose-dependent with respect to the concentration and volume of saline. Intrathecally administered (D-Pro2, D-Trp7,9)-SP, a substance P antagonist, dose-dependently blocked the behaviors induced by intrathecally administered substance P as well as those induced by intradermally injected hypertonic saline, indicating a possibly common final pathway at the spinal cord level for the manifestation of both behaviors. Hypertonic saline-induced behavior was blocked completely by morphine and a partial opiate agonist (pentazocine) in a dose-dependent manner, but was not blocked by another partial opiate agonist (nalorphine). The behavior was not blocked by non-steroidal anti-inflammatory agents. This nociceptive test, in conjunction with the substance P-induced behavior test, may allow discrimination between agents acting pre- or post-synaptically in the spinal cord. Baclofen, a GABAB agonist thought to act presynaptically, changed substance P-induced behavior and hypertonic saline-induced behavior in opposite directions.