The nociceptive study was carried out in the partial sciatic nerve ligation model of traumatic neuropathy, which is a well-established, highly reproducible, and easily performable model of neuropathic pain characterized by mechanical hyperalgesia [25 (link),26 (link)]. It is widely used to examine the effects of novel analgesic candidates for the unmet need of these medical conditions [27 (link),28 (link),29 (link),30 (link)].
Partial sciatic nerve ligation was performed in male NMRI mice under ketamine/xylazine (100/5 mg/kg, i.p.) anesthesia, as previously described [25 (link)]. Briefly, the ipsilateral common sciatic nerve was exposed high in the thigh region and one-third to one-half of the nerve thickness was tightly ligated using a siliconized silk suture (Ethilon 8-0, Ethicon, Somerville, NJ, USA). The wound was closed with a skin suture (Mersilk 4-0, Ethicon, Somerville, NJ, USA), and the animals were allowed to survive for 7 days, because significant mechanical hyperalgesia develops without postoperative pain component by this time point [20 (link)].
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