Therapeutics: Yes-associated protein 1 (YAP1; YAP); WW domain containing transcription regulator 1 (WWTR1; TAZ)

Rat studies suggest inhibiting YAP1 or its paralog WWTR1 could help treat neuropathic pain. In a rat model of peripheral nerve ligation-induced neuropathic pain, siRNA targeting YAP1 delayed the onset of mechanical allodynia and siRNA targeting YAP1 or WWTR1 decreased established mechanical allodynia, compared with scrambled siRNA. Also in the model, intrathecal injection of Visudyne verteporfin, a YAP1 inhibitor, delayed the onset of mechanical allodynia onset and decreased established mechanical allodynia compared with vehicle injection. Also in the model, intrathecal injection of an upstream pathway inhibitor that blocks activity of YAP and WWTR1 delayed the onset of thermal hyperalgesia and mechanical allodynia, and decreased established thermal hyperalgesia and mechanical allodynia. Next steps could include identifying and testing additional YAP1 or WWTR1 inhibitors in animal models of neuropathic pain...