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

Combination of guanfacine with opioid medication as a standard treatment for chronic pain.

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

Eligibility Criteria:
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.