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

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

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.