OBJECTIVES: To describe the potential for drug-drug interactions (DDIs) among patients with neck and back pain diagnoses categorized into neuropathic (NEURO), neuropathic and nociceptive(MIXED), nociceptive only (NOCI)or osteoarthritis(OA) cohorts.  METHODS: The PharMetrics US National managed care database was used to identify commercially insured patients 18 to 63 years of age with at least one claim for an opioid analgesic and a pre-existing study-related diagnosis, who were continuously eligible for services from 9/1/2006-8/31/2008. Patients who had nursing home care claims, drug/alcohol abuse, malignancy, and spine procedures, or pregnancy-related diagnoses were excluded.  Over the 2-year study period, the frequency of patients with at least 10 days of simultaneous availability of pain or pain-related prescriptions and medications that are known inhibitors or inducers of the cytochrome P450 (CYP) metabolic pathway was examined. RESULTS: The analysis identified 2,375 NEURO, 37,019 MIXED, 39,496 NOCI, and 6,124 OA patients. A high prevalence of coexisting medical conditions was found in all cohorts with 40%-74% of patients having diagnoses in at least 8 different disease categories.  Based on the 10-day simultaneous drug availability criterion, the potential for DDIs were identified in 26% of all patients during the 2-year observation period. This percentage was highest in the MIXED cohort (31%) and lowest in the NOCI cohort (20%).  Overall, potential inhibitor interactions were found in 20% of patients and potential inducer interactions were found in 11%. The CYP-2D6 substrates tramadol and oxycodone were the most frequent potential inhibitor interactions (5.6% and 5.9% of patients, respectively). Potential inducer DDIs were most commonly found in the CYP-1A2 pathway (8% of patients). CONCLUSIONS: Potential DDIs are common among patients taking pain medication.  Coexisting medical conditions and their treatment, and variations in the metabolism of different pain medications contribute to the complexity of selecting analgesics that would be expected to effectively treat pain.