The Journal of pharmacology and experimental therapeutics, Sep 13, 2016
To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute an... more To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the Adapter protein-2 Associated Kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase 1 formalin) but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin (STZ) model of diabetic peripheral neuropathy. Usi...
... Biol. 1: 31-65 (1994). [23] HR Jadhav, A. Singh, and KK Bhutani. Rationale for immunomodulato... more ... Biol. 1: 31-65 (1994). [23] HR Jadhav, A. Singh, and KK Bhutani. Rationale for immunomodulatory and anti-inflammatory effects of Ocimum sanctum: radical scavenging potential and effect on nitric oxide production, Acta. Hort. 678: 159-162 (2005). ...
The Journal of pharmacology and experimental therapeutics, Sep 13, 2016
To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute an... more To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the Adapter protein-2 Associated Kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase 1 formalin) but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin (STZ) model of diabetic peripheral neuropathy. Usi...
... Biol. 1: 31-65 (1994). [23] HR Jadhav, A. Singh, and KK Bhutani. Rationale for immunomodulato... more ... Biol. 1: 31-65 (1994). [23] HR Jadhav, A. Singh, and KK Bhutani. Rationale for immunomodulatory and anti-inflammatory effects of Ocimum sanctum: radical scavenging potential and effect on nitric oxide production, Acta. Hort. 678: 159-162 (2005). ...
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