Prolonged Analgesic Effect of PRF-108 and PRF-110 on Post-operative Pain in Pigs

Abstract

Introduction: Local anesthetic infusion techniques have been reported to reduce opiate requirements and pain scores following different kinds of surgery, including orthopedic surgery, inguinal hernia, and Cesarean surgery in women.

Methods: PRF-108 and PRF-110 formulations were applied to the wound space in an incisional model in pigs to test the hypothesis that these formulations have better and longer analgesic effects than the commercially available ropivacaine solution (Naropin(®), AstraZeneca).

Results: The data show significantly better analgesic activity with PRF-108 and PRF-110 compared to ropivacaine. The duration of the analgesic efficacy of PRF-108 and PRF-110 was at least five times longer than that was measured following treatment with ropivacaine. The data further suggest that active clearance from the injection site (the wound) is much slower for PRF-108 and PRF-110 than for the commercial ropivacaine solution.

Conclusion: Assessing the local concentration of PRF compounds and commercially available ropivacaine solution suggests that active clearance from the injection site (the wound) is much slower for PRF-108 and PRF-110 than for ropivacaine.

Funding: PainReform.

Keywords: Incision; PRF-108; PRF-110; Pain; Pig; Ropivacain; Surgery.

Fig. 1

Study design. The figure shows the study activity over a period of 48 h. However, six additional animals were observed for a period of 14 days at day 14. These animals were culled and the incision area was removed for wound healing analysis

Fig. 2

The effect of PRF-108, PRF-110, and Naropin on withdrawal force following von Frey testing. *P < 0.05 vs. sham-operated animals. EtOH ethanol, Ropi ropivacaine

Fig. 3

The effect of PRF-108, PRF-110 and Naropin on the duration of analgesia. PRF-108 and PRF-110 showed a significantly lower analgesia period, exceeding 24 h, vs. Naropin. *P < 0.05 vs. sham-operated animals. EtOH ethanol, Ropi ropivacaine

Fig. 4

Changes in ropivacaine plasma levels over time following PRF-108 or Naropin dosing

Fig. 5

Concentration of ropivacaine in the plasma (A) and the wound (B) 48 h post-treatment with PRF-108/4% ethanol, PRF-108/6% ethanol, PRF-110 or Naropin. *P < 0.05 vs. the Naropin-treated group. EtOH ethanol, Ropi ropivacaine

Fig. 6

Representative photographs of macroscopic observations. a A 7.5-cm-long sample from an animal treated with 4% ropivacaine/6% ethanol (Group 3). The incision is well apposed and visible up to a point. Sutures continue for approximately 1.8 cm beyond the visible incision (marked). Small dried scabs in suture holes and to a lesser degree along the entire visible incision. No thickening is noted. b A sample from an animal of the sham group (Group 1) with an 8.4-cm-long incision. The incision is well apposed and visible throughout, except in the 1 cm away from the mark where it is barely perceptible (marked). A slightly larger scab in approximately one-third of the incision line and small dried scabs limited to suture holes. No thickening is noted