CARES (Comprehensive Analgesic, Recovery, and Education Support) for Surgery Trial

INCLUSION CRITERIA:

* 18 to 75 years of age
* Able to speak, write, and read fluently in English
* Scheduled for elective surgery at

  * Stanford University Medical Center,
  * Brigham and Women's Hospital (Harvard University),
  * Atrium Health Wake Forest Baptist Medical Center (Wake Forest University), or
  * University of Kansas Medical Center
* Preoperative long-term opioid use (Defined as ≥ 60-day supply of opioids in the 180-day period prior to surgery), identified via self-report, state Prescription Drug Monitoring Program (PDMP), or Electronic Medical Records (EHR). Days may be nonconsecutive, and actual use of opioid supply is not required.
* Willing and able to complete online assessments and study calls independently
* On the preoperative Baseline assessments, least one of the following:

  * Current Opioid Misuse Measure (COMM-17): score ≥ 9
  * Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS-1): Reported use more frequent than "Never" on any item except Tobacco; for Tobacco, "Yes" to at least one item on the TAPS-2 for Tobacco
  * Alcohol Use Disorders Identification Test (AUDIT-C): score ≥4 (men), ≥3 (women)
  * Modified Brief Pain Inventory (mBPI): "Yes" to at least one of the following:

    * Over the past 24 hours have you needed to take your pain medication to help you sleep?
    * Have you taken any pain medications for any reason other than your pain, such as to reduce anxiety or improve mood?
    * Have you taken more pain medication than was prescribed to you in the past 24 hours?
* At the Post-Operative Call (7-13 days post-op): Postoperative daily opioid dose ≥ preoperative daily opioid dose (identified during the Pre-Surgery Call 5-1 day before surgery), measured in Morphine Milligram Equivalents (MME).

EXCLUSION CRITERIA

* Infection, tumor, or fracture at the operative site
* Allergy or intolerance to tizanidine
* Current use of tizanidine
* Renal impairment (Creatinine Clearance \[CrCl\] \< 25 ml/min)
* Hepatic impairment, including cirrhosis or elevated liver enzymes
* Concurrent use of other α2-adrenergic agonists, skeletal muscle relaxants
* Concurrent use of: fluvoxamine, ciprofloxacin,zileuton, fluoroquinolones, antiarrhythmics (amiodarone, mexiletine, propafenone, verapamil), cimetidine, famotidine, oral contraceptive pills, acyclovir, ticlopidine, and fexinidazole
* Pre-existing hypotension, sedation, dizziness, severe respiratory insufficiency.
* Opioid Use Disorder
* Suicidality as assessed by the Patient Health Questionnaire-9 (PHQ-9) Question 9 score ≥ 1
* Pregnancy, breastfeeding, or planning to conceive
* Planned cancer treatment in the \< 3 months following surgery
* Conditions causing inability to complete assessments (education, cognitive ability, mental status, medical status)
* Participating in another clinical trial with an active treatment arm