Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus)

Katechan Jampachaisri,Cholawat Pacharinsak,Monika K Huss,Alexandra Blaney,Bradley Taylor

doi:10.1371/journal.pone.0246213

Abstract

Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in a neonatal rat model of incisional pain. Male and female postnatal day 3 Sprague Dawley rat pups (n = 34) were randomly assigned to one of four treatment groups: 1) saline (control), 0.1 mL, once subcutaneously (SC); 2) buprenorphine HCl (Bup HCl), 0.05 mg/kg, once SC; 3) low dose Bup SR (low-SR), 0.5 mg/kg, once SC; 4) high dose Bup SR (high-SR), 1 mg/kg, once SC. Pups were anesthetized with sevoflurane and a 0.5-cm long skin incision was made over the left lateral thigh. The underlying muscle was dissected and closed using surgical glue. Thermal hypersensitivity testing was performed at 24 h prior to surgery and subsequently at 1, 4, 8, 24, and 48 h post-surgery using an infrared diode laser. Thermal hypersensitivity was attenuated at 1 h post-surgery in the Bup HCl group, while it was attenuated through the entire postoperative period in both low-SR and high-SR groups. This data suggests that a single dose of low-SR (0.5 mg/kg) or high-SR (1 mg/kg) effectively attenuates thermal hypersensitivity for at least 8 h in neonatal rat pups.

Highlights

Evaluation and management of pain in neonates is an area of increasing focus within both human and veterinary medicine
Thermal latency in this study was defined as time until purposeful movement away from the laser, and decreased latency correlated with thermal hyperalgesia
Withdrawal and behavioral response to noxious stimuli is seen in rat pups as early as postnatal day 1, and injection of irritating chemicals in rat pups at postnatal day 3 results in allodynia and hyperalgesia [23,24]

Summary

Introduction

Evaluation and management of pain in neonates is an area of increasing focus within both human and veterinary medicine. Prior to 1980, it was common for human neonatal patients to undergo invasive surgical procedures without adjunctive pain medication [1]. The prevailing belief during this time was that the neonatal nervous system was not developed enough to feel pain [2]. Indicates that neonates do experience pain, but that controlling pain early in life is critical to preventing lasting changes to developing somatosensory systems [3,4,5]. A number of analgesic agents have been evaluated in neonates and infants, including topical anesthesia, acetaminophen, and opioids [6].

Objectives

Methods

Results

Conclusion