Intervention: Morphine Sulfate
Trial phase: Phase 4
SMILES: CN1CCC23c4c5ccc(O)c4OC2C(O)C=CC3C1C5.CN1CCC23c4c5ccc(O)c4OC2C(O)C=CC3C1C5.O=S(=O)(O)O
Sex: Male
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 8
Group description: Participants will receive MS Contin over a 4 week period starting at 15 mg bid. Doses will titrated upwards as tolerated by increments of 15-30 mg to a highest attained dose or a maximum dose of 90 mg

MS Contin
Eligibility criteria:
-INCLUSION CRITERIA:

Clinical evidence of chronic OA by history, examination and radiological examination

a. Pain level of 4/10 or greater on a scale of 0 to 10 over a 2 week screening period
b. Pain for a duration of 3 months or longer present at least 5 out of 7 days a week by history
c. Radiographic evidence of moderate to severe OA in at least one joint selected for study based on the Kellgren and Lawrence scoring scale (Appendix I:Table 2)
Age between 30-65 at study entry. This age range was chosen as osteoarthritis is rare in people younger than 30 and to minimize the effect of the neuroendocrine changes associated with aging on study outcome measures.
Men of all ethnicities
Ability to provide his own consent and to cooperate with study procedures
Willingness to refrain from drinking alcohol during the study because alcohol may exacerbate the sedative effects of morphine
Willingness to refrain from using muscle relaxers, antiepileptic medications and antidepressants within 6 weeks of starting study procedures
Willingness not to be on opioids other than prescribed by the study for the duration of the study and willingness to come off of opioids six weeks prior to starting study procedures

EXCLUSION CRITERIA:

Impaired pulmonary, renal, hepatic, cardiovascular or endocrine-metabolic function or major coexisting medical condition such as cancer, Cushing s disease, and diabetes which may make participation unsafe or interfere with hormone measurements
Prostatic disease or hypertrophy which would make subjects prone to urinary retention or require medication that would interfere with study hormone measurements
Sexual dysfunction including lack of libido, impotence or erectile abnormalities for safety reasons as these symptoms may be worsened by morphine
Rheumatoid arthritis other types of inflammatory arthritis
Use of systemic corticosteroids in the two months before study entry which might interfere with study hormone measurements
Present or past history of alcohol dependence which might predispose subjects to problems with opioid dependence based on 2 or more positive responses to the CAGE questionnaire (the latter group will be referred to psychiatry for further evaluation and excluded from study if found to fulfill psychiatric criteria for alcohol dependence or abuse)
Current usage of any recreational or unauthorized prescription drugs because this may indicate abuse potential based on positive urine drug test at study screening visit
History of opioid abuse at any time in the past based on patient report or a urine drug screen positive for opioids
Major depression based on a score of greater than or equal to 20 on the Beck Depression Inventory at screening, present history of major depression or treatment for major depression because these may effect endocrine function
Hct < 35; anemia or bleeding disorder because subjects will undergo serial blood sampling to assess hormone function
Allergy or inability to tolerate to morphine
Current or past fibromyalgia according to Wolfe criteria (1990)
Present or past history of sleep apnea because of increased risk of respiratory depression with morphine
Body mass index (BMI) > 30kg/m(2) and BMI < 20kg/m(2)
Local steroid injections during the study because weight has significant effects on hormone levels
Addition of or changes to complementary or alternative treatments during the study