This is a double-blind, placebo-controlled, randomized, crossover trial aimed at assessing the effect of gabapentin and tizanidine, two pain medications, on insomnia in chronic pain patients.

Chronic pain and insomnia are highly prevalent conditions affecting 10-25% and 6-10% of the general population, respectively. Importantly, these two conditions frequently co-occur, with 50-80% of chronic pain patients reporting sleep disturbances. Identifying medication that alleviates pain and insomnia simultaneously may help reduce risks associated with polypharmacy, including drug-drug interactions.

In this double-blind, placebo-controlled, randomized, crossover trial, gabapentin and tizanidine, two drugs which are respectively commonly used to treat neuropathic and musculoskeletal pain, will be compared to each other and to placebo in their ability to alleviate insomnia in chronic pain patients.

In each week, patients will receive 3-night (Friday-Sunday) trials each of placebo, gabapentin or tizanidine in a randomized, double-blind order and will monitor their insomnia using the Athens Insomnia Scale (AIS) questionnaire (adapted to fit the time frame of this trial). The primary outcome consists of the difference in mean AIS scores between the 3 treatments at the primary time point, which is Monday of each week (after 3 nights of drug intake).

Patients will also monitor their sleepiness, pain relief and overall improvement as secondary variants using the Stanford Sleepiness Scale (SSS), Visual Analog Scale (VAS), and Patient's Global Impression of Change (PGIC) questionnaires respectively.

Scores on the Monday preceding the first treatment will serve as baseline and the period between treatments (i.e. Monday-Thursday nights) will serve as a 4-day washout period between treatments.

Our hypothesis is that gabapentin and tizanidine will both be more effective than placebo in alleviating insomnia in chronic pain patients but will not be different from one another.

Inclusion Criteria:

• BMI ≤ 35
• Any ethnicity
• Must be able to communicate in English
• Must have access to email and be able to respond to REDCap questionnaires in English
• Has a chronic pain condition (≥ 3 months of pain)
• Reports sleep disturbance and scores ≥ 6 on AIS questionnaire
• Ability to provide informed consent

Exclusion Criteria:

• Pregnancy
• Breastfeeding
• Has diagnosis of chronic kidney disease
• Has known QT prolongation >500 msec on prior EKG
• Inability to complete daily questionnaires
• Allergy to, or intolerance of, any of tizanidine or gabapentin
• Shift workers
• Anticipated travel across multiple time zones (jetlag) during the duration of the trial
• Circadian misalignment
• Prior syncope experience and/or fear of blood/needles (if a blood draw is required)

Deidentified data will be shared in a manner TBD based on funding availability and journal requirements.

Beginning 12 months and ending 3 years following article publication.

Researchers who provide a methodologically sound proposal. Proposals should be sent to nmschuster@health.ucsd.edu.

Each participant will have an identification number and randomization of drug sequence allocation will be performed a priori using a random number generator by the study pharmacist. The 3 treatments will be identically encapsulated by the study pharmacist. The study pharmacist will place the drug capsules in identical sealed plastic bags labeled "Treatment 1" through "Treatment 3".