Effect of Guanfacine on the Reversal of Opioid-induced Hyperalgesia (OIH)

Inclusion Criteria

• 18-65 years old

• Chronic neck or back pain condition for at least 6 months

• VAS score of 4-8, despite opioid therapy

• On a stable morphine equivalent dose of at least 60mg/day and ≤ 240mg/day for at least 3 months

Exclusion Criteria

• Has taken Methadone, Suboxone, Fentanyl, and/or Tramadol in the last six (6) months

• Has taken guanfacine (or other alpha-2AR agonists) in the last six (6) months

• Changes to current or adding new pain treatment while enrolled in the study (i.e. opiates, epidural steroid injection) will be reviewed by the study physician

• Unable to independently provide informed written consent

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

• Intolerable allergies or has had a severe adverse reaction to study medication (i.e. guanfacine, lactose, vitamin B2 a.k.a. riboflavin)

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

• Pregnant or breastfeeding

• Pending litigation related to neck or back pain

• 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 severe cardiovascular disease (i.e. arrhythmia - prolonged QT interval > 440ms), cerebrovascular disease/accident (i.e., stroke), 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) will be reviewed by a study physician

• Bradycardia (resting heart rate < 60 bpm) will be reviewed by a study physician

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

• Tests positive for 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 currently prescribed 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 as well as possible confounding side effects. 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 guanfacine.