Paw withdrawal threshold in response to application of von Frey filaments before spinal nerve ligation is 22.6±2.4 g. The mechanical threshold decreases significantly (2.3±0.5 g, P<0.05) within 10 days after nerve ligation and remains stable for at least 8 weeks. Intrathecal injection of 5 to 30 μg of L-APB significantly increases the paw withdrawal threshold in response to application of von Frey filaments in eight nerve-ligated rats in a dose-dependent manner. The maximal effect of L-APB appears within 45 min and gradually subsided in 120 min following intrathecal administration[2].
In Vitro
Kinase Assay
Cell Assay
Animal Administration
Rats[2] The effect of L-APB (L-AP4: 5, 10, and 50 μM) on identified ascending dorsal horn neurons is studied in 20 L5 and L6 spinal nerve ligated rats. L-APB, starting with the lowest concentration, is applied topically onto the exposed spinal cord. Five to 10 min following L-APB application, the response of neurons to graded mechanical stimuli is re-examined. To ensure that the effect of L-APB on dorsal horn neurons is through group III mGluRs, the inhibitory effect of 50 μM L-APB is tested before and after topical application of 100 μM MAP4, a specific antagonist for group III mGluRs, in another 12 dorsal horn neurons. MAP4 is applied to the recording site 10 min before application of 50 μM L-APB. In addition, to determine whether topical application of L-APB affects ascending dorsal horn neurons in normal rats, the effect of 50 μM L-APB on spontaneous and evoked responses to graded mechanical stimuli is examined in 11 dorsal horn neurons from eight normal rats. Also, the effect of topical spinal application of 100 μM MAP4 alone on these cells is tested 15 to 20 min after washout of L-APB solution from the recording site[2].
References
[1]. Selvam C, et al. Increased Potency and Selectivity for Group III Metabotropic Glutamate Receptor Agonists Binding at Dual sites. J Med Chem. 2018 Mar 8;61(5):1969-1989.
[2]. Chen SR, et al. Distinct roles of group III metabotropic glutamate receptors in control of nociception and dorsal horn neurons in normal and nerve-injured Rats. J Pharmacol Exp Ther. 2005 Jan;312(1):120-6.
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