Patients will get an injection of either SKY0402 or placebo during hemorrhoid surgery, and their pain and pain medicine use will be monitored.

Inclusion Criteria:

• Age > 18 years of age at the Screening visit
• American Society of Anesthesiologists (ASA) class 1-3
• Scheduled to have a two or three column excisional hemorrhoidectomy under general anesthesia using the Milligan-Morgan technique
• For female subjects, surgically sterile or at least two years menopausal, or using an acceptable method of birth control; must have a documented negative blood or urine pregnancy test within 24 hours before surgery
• Clinical lab values less than or equal to twice the upper limit of normal or, if abnormal, deemed not clinically significant per the Investigator.
• Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments
• Able to speak, read, and understand the language of all subject-facing documents, including the ICF and study questionnaires
• Able and willing to comply with all study visits and procedures

Exclusion Criteria:

• Single-column hemorrhoidectomy or hemorrhoidectomy without an internal component
• Body weight less than 50 kilograms (110 pounds)
• History of hypersensitivity or idiosyncratic reactions or amide-type local anesthetics, opioids, or propofol
• Current painful physical condition or concurrent surgery other than hemorrhoids that may require analgesic treatment (such as non-steroidal anti-inflammatory drug [NSAID], opioid, selective serotonin reuptake inhibitor [SSRI], tricyclic antidepressant, gabapentin, pregabalin) in the postoperative period for pain that is not strictly related to the hemorrhoidectomy procedure and may confound the postoperative assessments
• Concurrent fissurectomy
• Use of any NSAID including selective COX-2 inhibitor, opioid, SSRI, tricyclic antidepressant, gabapentin, or pregabalin within three days of surgery
• Use of acetaminophen within 24 hours of surgery
• Chronic users of analgesic medications, including taking opioid medications for more than 14 days in the last 3 months, or non-opioid pain medications more than 5 times per week
• History of, suspected, or known addiction to or abuse of drugs or alcohol within the past two years
• Current use of glucocorticosteroids or use of glucocorticoids within one month of enrollment into this study
• HIV infection or hepatitis
• Currently pregnant, nursing, or planning to become pregnant during the course of the study or within one month of study drug administration
• Any psychiatric, psychological, medical, or laboratory condition that the investigator feels makes the subject an inappropriate candidate for this clinical trial
• Subjects who have received another investigational drug within the longer of the last 30 days or 10 elimination half-lives
• Previous participation in a SKY0402 study
• Failure to pass drug and alcohol screen