Effects and underlying mechanisms of endotoxemia on post-incisional pain in rats

Aims: The aimof the present studywas to investigate the effects and underlying mechanisms of endotoxin (lipopolysaccharide, LPS) on postoperative pain using a rat model of incisional pain. Main methods: Animalswere assigned to one of four groups using a 2 x 2 experimental design: a single intraperitoneal injection of 5mg/kg LPS versus vehicle, by plantar incision versus anesthesia alone. Spontaneous pain and mechanical pawwithdrawal threshold (PWT) were evaluated using Rat Grimace Scale (RGS) and von Frey fibers, respectively. Analgesic effects of ketoprofen, morphine, and wound infiltration with ropivacaine, as well as the contribution of the Toll-like receptor (TLR) 4 pathway, were also evaluated. In vivo single fiber recordings were performed to assess the nociceptive afferent signals from the surgical site. Key findings: Systemic administration of LPS significantly increased the pain intensity at 2 h after hind paw incision, but did not affect the PWT. The duration of post-incisional pain assessed by both scales did not significantly differ in the presence or absence of LPS. The analgesic efficiency of ketoprofen andmorphinewas reduced by LPS, while that ofwound infiltrationwith ropivacainewas preserved. On the other hand, in vivo single fiber recording failed to demonstrate any significant effects of LPS on the activity of primary afferents due to mechanical stimuli. Pre-treatment with intrathecal LPS from Rhodobacter sphaeroides, a TLR-4 antagonist, almost completely inhibited LPS-induced exacerbated post-incisional pain, and decreased analgesic responsiveness. Significance: The present results suggested that LPS exacerbates post-incisional pain via the central TLR-4 pathway. (C) 2016 Elsevier Inc. All rights reserved.