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

• Heat Pain Threshold [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  The investigators will measure the heat pain threshold using Quantitative Sensory Testing (QST). The testing will be done at three of the four visits.
• Heat Pain Tolerance [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  The investigators will measure the heat pain tolerance using Quantitative Sensory Testing (QST). The testing will be done at three of the four visits.
• Temporal Pain Summation [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  The investigators will measure the temporal pain summation using Quantitative Sensory Testing (QST). The testing will be done at three of the four visits.
• Detecting Diffuse Noxious Inhibitory Control (DNIC) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  The investigators will detect the Diffuse Noxious Inhibitory Control (DNIC) using Quantitative Sensory Testing (QST). The DNIC is when pain A is lessened by or inhibited by another pain B. The testing will be done at three of the four visits.
• Needle Stick Test [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  The investigators will measure the subject's pain score before and after the subcutaneous needle stick. The testing will be done at three of the four visits.

• Heat Pain Threshold [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  We will measure the heat pain threshold using the QST. The testing will be done at three of the four visits.
• Heat Pain Tolerance [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  We will measure the heat pain tolerance using the QST. The testing will be done at three of the four visits.
• Temporal Pain Summation [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  We will measure the temporal pain summation using the QST. The testing will be done at three of the four visits.
• Detecting DNIC [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  We will detect the DNIC using the QST. The testing will be done at three of the four visits.
• Needle Stick Test [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  We will measure the subject's pain score before and after the subcutaneous needle stick. The testing will be done at three of the four visits.

Dual medication (guanfacine and morphine) as a standard treatment for chronic pain.

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.

• Drug: Guanfacine

  Subjects will be randomized into 1 of the following 5 treatment groups:

  1. guanfacine (2mg): morphine
  2. guanfacine (1mg): morphine
  3. guanfacine (2mg): placebo
  4. morphine: placebo
  5. placebo:placebo

  To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 10 weeks of drug treatment (combination or placebo).

• Drug: Morphine

  Subjects will be randomized into 1 of the following 5 treatment groups:

  1. guanfacine (2mg): morphine
  2. guanfacine (1mg): morphine
  3. guanfacine (2mg): placebo
  4. morphine: placebo
  5. placebo:placebo

  To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 10 weeks of drug treatment (combination or placebo).

• Drug: Placebo

  Subjects will be randomized into 1 of the following 5 treatment groups:

  1. guanfacine (2mg): morphine
  2. guanfacine (1mg): morphine
  3. guanfacine (2mg): placebo
  4. morphine: placebo
  5. placebo:placebo

  To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 10 weeks of drug treatment (combination or placebo).

• Active Comparator: Guanfacine:morphine

  Subjects will be randomized into 1 of the following 5 treatment groups:

  1. guanfacine (2mg): morphine
  2. guanfacine (1mg): morphine
  3. guanfacine (2mg): placebo
  4. morphine: placebo
  5. placebo:placebo

  Subjects who are randomized into the guanfacine:morphine groups will be compared to the placebo-mixed or placebo only groups.

  Interventions:

  • Drug: Guanfacine
  • Drug: Morphine
• Placebo Comparator: Placebo

  Subjects will be randomized into 1 of the following 5 treatment groups:

  1. guanfacine (2mg): morphine
  2. guanfacine (1mg): morphine
  3. guanfacine (2mg): placebo
  4. morphine: placebo
  5. placebo:placebo

  Subjects who are in the placebo-mixed or placebo only groups will be compared to the guanfacine:morphine groups.

  Interventions:

  • Drug: Guanfacine
  • Drug: Morphine
  • Drug: Placebo

Inclusion Criteria:

1. back and neck pain refers to pain resulting from conditions such as degenerative facet joint disease, degenerative disc disease, radiculitis, or post-laminectomy pain syndrome; and
2. abdominal and pelvic pain includes pain due to chronic pancreatitis, endometriosis, etc.
3. subjects are 18 to 65 years of age,
4. subjects have a pain condition described above for at least six months and a VAS score of 5 or above, and
5. subjects have not received guanfacine (or other alpha-2AR agonists) or opioid treatment for at least the past 6 months.

Exclusion Criteria:

1. have sensory deficits at the site of QST or have Raynaud's syndrome,
2. have pending litigation related to chronic pain condition,
3. are on a methadone or suboxone maintenance program for addiction treatment d) currently in a treatment program for alcohol abuse,

e) have major psychiatric disorders that required hospitalization in the past 6 months such as major depression, bipolar disorder, schizophrenia, anxiety disorder, or psychotic disorders, f) are using illicit drugs, recreational drugs, or drugs not prescribed to them as detected by a urine toxicology/drug screen, g) are pregnant or lactating; h) allergic to opioid or guanfacine, i) are on such drugs as valproic acid, antibiotics, antifungal drugs, St. John wort, ACE inhibitors, nefazodone (antidepressant), calcium channel blockers, HIV or AIDS medications, seizure medications, or alpha2-AR agonists and j) have hypotension or bradycardia.