Efficacy of an Investigational Small Molecule for Pain After Colorectal Surgery

Open wound during a surgical operation.
The efficacy of a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A was investigated for postoperative pain after colorectal surgery.

Treatment with VVZ-149, a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A, resulted in a nonsignificant reduction of postoperative pain 8 hours after colorectal surgery. A post hoc analysis, however, suggested it may be beneficial in patients with negative affect who have higher postoperative opioid use. These findings were published in Journal of Clinical Anesthesia.

Patients (N=52) undergoing laparoscopic colorectal surgery between 2015 and 2016 at 3 centers were recruited for this randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT02489526). Patients were randomized 2:1 to receive either VVZ-149 (n=36) or placebo (n=16) administered via intravenous infusion for 8 hours after emergence from anesthesia. Opioid consumption and pain on an 11 point Numerical Rating Scale (NRS) were assessed up to 24 hours.

Patients were aged mean 53.98±11.82 years and 93.3% were White.

Total opioid consumption during the first 2 (P =.046), 6-8 (P =.007), 8-9 (P =.015), and 8-12 (P =.020) hours was significantly lower among the VVZ-149 cohort. By 24 hours, the opioid consumption was 34.2% lower (mean difference, -3.12; 95% CI, -5.7 to  -0.5 mg; P =.020).

Patient-controlled analgesia was significantly lower among the VVZ-149 cohort at 0-2 (P =.019), 2-4 (P =.011), 6-8 (P <.001), 8-9 (P =.003), and 9-12 (P =.001) hours. Median demands over 12 hours were significantly reduced (20.5 vs 40.5; P =.002).

The amount of rescue dosing during the first 2 hours was correlated with predose pain intensity (r, 0.359; P =.009) and patient-controlled analgesia demand (r, 0.313; P =.024) which was itself correlated with preoperative anxiety (r, 0.417; P =.002).

Differences in VVZ-149 efficacy were observed for opioid consumption among patients who did and did not require rescue. Patients who received VVZ-149 and required rescue consumed 40% fewer opioids than placebo recipients (mean difference, -2.2; 95% CI, -4.4 to -0.0 mg; P =.048). The difference in opioid consumption among the nonrescued cohort did not reach significance.

Adverse events were reported by 92.5% of the VVZ-149 and 80.0% of the placebo cohorts. Rehospitalization occurred among three VVZ-149 and one placebo recipient due to postoperative ileus, one VVZ-149 patient due to acute kidney injury, and one VVZ-149 recipient due to infection. Events possibly associated with study drug occurred among 40.0% of both cohorts. VVZ-149 recipients reported more somnolence (45% vs 25%) and headache (25% vs 5%).

This study was ended prematurely due to slow recruitment and was likely under powered.

VVZ-149 may have a beneficial effect among patients who require rescue following surgery and may decrease opioid consumption among the subset of patients at increased risk. Additional larger trials are needed.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Nedelijkovic SS, Song I, Bao X, et al. Exploratory study of VVZ-149, a novel analgesic molecule, in the affective component of acute postoperative pain after laparoscopic colorectal surgery. J Clin Anesth. 2022;76:110576. doi:10.1016/j.jclinane.2021.110576