Effect of Guanfacine on Opioid-induced Hyperalgesia (OIH) and Tolerance

This aim proposes that guanfacine would be a useful drug to deter Opioid-Induced Hyperalgesia
(OIH) when combined with an opioid (morphine) in chronic pain management.

Inclusion Criteria

- 18-65 years old

- Chronic neck or back pain condition for at least 3 months

- VAS score of 4-8

- Has not taken an opioid for the last 3 months

- Has not taken guanfacine (or other alpha-2AR agonists) for the last 6 months

Exclusion Criteria

- Sensory deficits at site of QST, such as peripheral neuropathy

- Allergic to or has had a severe adverse reaction to study medication (i.e. opioids,
guanfacine, lactose, vitamin B2 a.k.a. riboflavin)

- Cannot tolerate study drugs' maximum doses

- Takes vitamin B2 > 1.6mg/day during the study

- Pregnant or breastfeeding

- Pending litigation

- Diagnosed with Raynaud's syndrome

- Has other chronic pain conditions such as fibromyalgia or joint osteoarthritis that
are predominant over back and neck pain with regard to its intensity (VAS)

- Has known pre-existing cardiovascular disease (i.e. arrhythmia - prolonged QT interval
> 440ms), cerebrovascular disease, hepatic or renal impairment, CNS condition,
metabolic condition, or history of syncope

- Hypotension (SBP < 90 mmHg and DBP < 60 mmHg for female or SBP < 100 mmHg and DBP < 60
mmHg for male; measured while in a sitting position) or bradycardia (resting heart
rate < 60 bpm)

- Subjects are on antihypertensive drugs (e.g., a beta-blocker) that result in
hypotension and/or bradycardia as defined above

- Tests positive for non-study opioids, illicit drugs, marijuana, or non-prescribed
drugs

- Major psychiatric disorders that required hospitalization in the past 6 months such
as: major depression, bipolar disorder, schizophrenia, anxiety disorder, or psychotic
disorders

- Currently in a treatment program for alcohol or drug abuse, or currently on methadone
or buprenorphine (i.e. suboxone, subutex) for treatment of addiction, or stimulants
for treatment of ADHD

- History of substance or alcohol abuse (meets DSM IV criteria) per medical record or
subject admission

- Subjects are on medications that serve as CYP3A4/5 inhibitors or CYP3A4 inducers
including, but are not limited to, valproic acid, macrolide antibiotics, antifungal
drugs, St. John wort, ACE inhibitors, nefazodone (antidepressant), calcium channel
blockers, H2-receptor antagonists, anti-HIV or AIDS drugs, and antiepileptic drugs

- Subjects are on medications that are ligands for alpha2-adrenergic receptors including
antipsychotic drugs (e.g. clozapine) and tricyclic or tetracyclic antidepressants
(e.g. imipramine, mirtazapine, mianserin). Any medications taken by a subject at the
enrollment will be reviewed regarding their compatibility with guanfacine and morphine
as well as possible confounding side effects. In addition, subjects will be warned of
side effects of morphine such as sedation, respiratory depression at the enrollment.
Subjects will be allowed to take non-opioid pain medications except for gabapentinoids
and amitriptyline/nortriptyline as far as such medications do not have incompatibility
with morphine and guanfacine.