Pain and Opioid Addiction: A Systematic Review and Evaluation of Pain Measurement in Patients with Opioid Dependence on Methadone Maintenance Treatment.

BACKGROUND: While chronic pain has been said to impact patient's response to methadone maintenance treatment for opioid dependence, the reported findings are inconsistent. These discrepancies may be a direct result of variations in the measurement of chronic pain or definitions of response to methadone treatment. The goal of this study is to evaluate the association between pain and substance use behaviour to determine the real impact of comorbid pain in the methadone population. We also aim to examine sources of variation across the literature with a specific focus on the measurement of pain. METHODS/DESIGN: We performed a systematic review using an electronic search strategy across CINAHL, MEDLINE, Web of Science, PsychINFO, EMBASE, and the Cochrane Library including Cochrane Reviews and the Cochrane Central Register of Controlled Trials databases. Title, abstract, as well as full text screening and extraction were performed in duplicate. Studies evaluating the association between chronic pain and methadone maintenance treatment response were eligible for inclusion in this review. Using a sample of 297 methadone patients from the Genetics of Opioid Addiction (GENOA) research collaborative, we assessed the reliability of patient self-reported pain and the validated Brief Pain Inventory (BPI) assessment tool. RESULTS: After screening 826 articles we identified five studies eligible for full text extraction, of which three showed a significant relationship between the presence of pain and the increase in substance abuse among patients on methadone for the treatment of opioid dependence. Studies varied largely in the definitions and measurement of both pain and response to treatment. Results from our validation of pain measurement in the GENOA sample (n=297) showed the use of a simple self-reported pain question is highly correlated to the use of the BPI. Simply asking patients whether they have pain showed a 44.2% sensitivity, 88.8% specificity, 84.4% PPV and 53.6% NPV to the BPI. The area under the ROC curve was 0.67 and the Pearson χ(2) was 37.3; (p<0.0001). DISCUSSION: The field of addiction medicine is at a lack of consensus as to the real effect of chronic pain on treatment response among opioid dependent patients. Whether it be the lack of a single "gold standard" measurement of response, or a lack of consistent measurement of pain, it is difficult to summarize and compare the results of these relatively small investigations. In comparison to the BPI, use of the simple self-reported pain has lower sensitivity for identifying patients with pain, suggesting the inconsistencies in these studies may result from differences in pain measurement. Future validation studies of pain measurement are required to address the predictive value of self-reported pain.

T cell-mediated immunity to oncornavirus-induced tumors. III. Specific and nonspecific suppression in tumor-bearing mice.

A strong cell-mediated immune response against Friend, Moloney, Rauscher virus-induced (FMR) cell surface antigens has been demonstrated previously in mice which reject oncornavirus-induced tumors. In order to identify an eventual suppressor mechanism in animals with progressively growing tumors, experiments were initiated in C57BL/6 mice bearing either a murine sarcoma virus (MSV) tumor or Moloney virus-induced lymphoma (MBL2). Progressive tumor growth was induced (a) in viremic animals first infected with Moloney murine leukemia virus (M.Mu LV), then inoculated as adult with MSV; (b) in nonviremic animals injected with MBL2 lymphoma cells. In the absence of tumor cells, viremia induces specific tolerance for which there is no evidence for suppressor cells. In tumor-bearing mice, specific suppressor T cells are detected which are able to inhibit the generation of anti-FMR cytolytic T lymphocytes in vitro and enhance the tumor growth in vivo. In addition to the specific suppressor T cells, a nonspecific suppressive activity mediated by metastatic T lymphoma cells is demonstrated in the spleens of lymphoma-bearing animals. The respective role of the virus and tumor cells in the induction of tolerance to M.MuLV-induced antigens, and their relationship to other components of the specific cell-mediated immune response is discussed.

T cell-mediated immunity to oncornavirus-induced tumors. IV. Preliminary evidence for a specific suppression of anti-Moloney cell-mediated immune response by autoimmune T cells.

Previous reports have demonstrated that adult C57BL/6 mice infected with murine sarcoma virus (MSV) develop a strong cell-mediated immune response against Friend, Moloney, Rauscher virus-induced type-specific (FMR) antigens and reject their tumors. To demonstrate a possible role for auto-anti-MSV T blasts, syngeneic C57BL/6 mice were immunized with highly enriched anti-FMR cytolytic T cells. One of 3 pools of these autoimmune T cells prepared from 12 surviving immunized mice (a) inhibited specifically the in vitro anti-MSV cytolysis generation and (b) enhanced drastically the MSV tumor growth in vivo. The possibility for such an immunization procedure to induce anti-idiotype T cells, the repeatability of this effect and the relationship of the suppressor cells with antigen-specific suppressor cells and other components of the anti-MSV immune response are discussed.