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

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 enroll…