Novel analgesic SBS-1000 does not alter survival or cardiorespiratory responses after extremity trauma and moderate hemorrhage in rats

Objective: Novel analgesics used for acute pain relief in both the military and civilian settings must have minimal or no secondary effects, especially on the cardiovascular and respiratory systems, when the pain of trauma is associated with hemorrhage. Sparian Biosciences has developed an N-arachidonoylethanolamine receptor agonist, SBS-1000, that has “opioid-like” analgesic efficacy but lacks “opioid-like” side effects, like respiratory depression and tolerance. However, the effects of SBS-1000 on cardiovascular and respiratory responses after hemorrhage (HEM) associated with trauma are unknown. Thus, the objective of this study is to test effects of an analgesic dose of SBS-1000 on cardiorespiratory responses and survival in an animal model of battlefield trauma and HEM. We hypothesized that, when given after trauma and HEM, SBS-1000 will suppress cardiorespiratory responses to HEM by 30% or more and thereby decrease survival. Methods: Male rats were anesthetized with isoflurane and implanted with a telemetry transmitter to measure mean arterial pressure (MAP) and heart rate (HR); buprenorphine sustained release was used to relieve pain associated with surgical procedures. Following 2 weeks recovery, rats were anesthetized with isoflurane, and a carotid catheter was implanted. No analgesics were used to relieve the pain associated with catheter implantation to exclude associated confounding factors during experiment day. The next day, rats were briefly anesthetized to perform extremity trauma (ET; fibular fracture + hindlimb soft tissue crush injury) and were allowed to recover 90 min before starting conscious HEM (time = 0-25 min) within a plethysmograph to measure respiratory rate (RR), tidal volume (TV), and minute ventilation (MV). HEM was moderate and consisted of 37% of total blood volume. Rats received either 1) vehicle (VEH, 10% DMS, 10% Kolliphor, 80% Saline) or 2) SBS-1000 (1 mg/kg in VEH) via subcutaneous injection into the animal’s back after HEM (t = 25 min). The study continued for 215 minutes (time = 25-240 min). Data are mean ± standard deviation (SD). Results: There were no differences between groups in MAP, HR, RR, TV, MV at either baseline (t = 0 min), end of HEM (t = 25 min), or after VEH/SBS-1000 injection (t = 25-240 min). 100% of animals in VEH (n=8) and SBS-1000 (n=9) groups survived. Conclusion: An analgesic dose of SBS-1000 did not affect cardiorespiratory responses or survival following ET and HEM. SBS-1000 is a promising novel analgesic that may prove useful in the battlefield or civilian sector to reduce pain from trauma in the presence of moderate hemorrhage. Future studies will investigate the effects of SBS-1000 after a more severe level of hemorrhage. Funding Source: Congressionally Directed Medical Research Program (CDMRP) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.