The journal of pain : official journal of the American Pain Society
-
ClinicalTrials.gov is a registry and results database of federally and privately supported clinical trials conducted worldwide. We sought to answer: what are the characteristics of pain trials; how frequently are these trials stopped and why; what is the magnitude of attrition due to lack of efficacy or adverse events; and whether the withdrawal rates depend on pain syndrome. To facilitate this and subsequent studies, we have developed a system called Sherlock that automatically downloads data from ClinicalTrials.gov into a relational database. We included pain interventional trials. To evaluate attrition, we restricted consideration to prospective randomized, parallel, double-blind, placebo-controlled trials. Of the 82,867 trials, 6% reported results and 5.6% terminated before the planned number of subjects was accrued. Of these early terminations, 38% were due to enrollment difficulties. In the placebo arms, 3.8% of participants withdrew due to lack of efficacy and 4.9% due to adverse events, with proportions differing among pain conditions. Compared with migraine trials, in fibromyalgia trials 5.1% more participants withdrew due to lack of efficacy (95% confidence interval [CI], 2.5-7.8%), and 6.4% more withdrew due to adverse events (95% CI, 4.3-8.6%). Nonsteroidal anti-inflammatory drugs were the treatment class with the lowest adverse events withdrawals. Recruitment challenges account for the largest proportion of noncompleted trials. Attrition rates differ across pain conditions. Migraine studies had the lowest withdrawal rate. Tools like Sherlock facilitate conducting research in the ClinicalTrials.gov registry. ⋯ ClinicalTrials.gov registry enables researchers to get a snapshot of a specific field and observe changes over time in trial design, including numbers of subjects accrued, and it can inform clinical trial design. We learned that recruitment challenges account for the largest proportion of noncompleted trials, attrition rates differed across pain conditions, and migraine studies had the lowest withdrawal rate.
-
Despite the increasing use of opioid analgesics for chronic pain management, it is unclear whether opioid dose escalation leads to better pain relief during chronic opioid therapy. In this study, we retrospectively analyzed clinical data collected from the Massachusetts General Hospital Center for Pain Medicine over a 7-year period. We examined 1) the impact of opioid dose adjustment (increase or decrease) on clinical pain score; 2) gender and age differences in response to opioid therapy; and 3) the influence of clinical pain conditions on the opioid analgesic efficacy. A total of 109 subjects met the criteria for data collection. We found that neither opioid dose increase, nor decrease, correlated with point changes in clinical pain score in a subset of chronic pain patients over a prolonged course of opioid therapy (an average of 704 days). This lack of correlation was consistent regardless of the type of chronic pain including neuropathic, nociceptive, or mixed pain conditions. Neither gender nor age differences showed a significant influence on the clinical response to opioid therapy in these subjects. These results suggest that dose adjustment during opioid therapy may not necessarily alter long-term clinical pain score in a group of chronic pain patients and that individualized opioid therapy based on the clinical effectiveness should be considered to optimize the treatment outcome. ⋯ The study reports a relationship, or lack thereof, between opioid dose change and clinical pain score in a group of chronic pain patients. The study also calls for further investigation into the effectiveness of opioid therapy in the management of chronic nonmalignant pain conditions.
-
Multiple investigators have recently asked whether neuroimaging has shown that chronic pain is a brain disease. We review the clinical implications of seeing chronic pain as a brain disease. Abnormalities noted on imaging of peripheral structures have previously misled the clinical care of patients with chronic pain. We also cannot assume that the changes associated with chronic pain on neuroimaging are causal. When considering the significance of neuroimaging results, it is important to remember that "disease" is a concept that arises out of clinical medicine, not laboratory science. Following Canguilhem, we believe that disease is best defined as a structural or functional change that causes disvalue to the whole organism. It is important to be cautious in our assertions about chronic pain as a brain disease because these may have negative effects on 1) the therapeutic dialogue between clinicians and patients; 2) the social dialogue about reimbursement for pain treatments and disability due to pain; and 3) the chronic pain research agenda. Considered scientifically, we may be looking for the cause of chronic pain through neuroimaging, but considered clinically, we are in fact often looking to validate pain complaints. We should not yield to the temptation to validate pain with the magnetic resonance imaging scanner (structural or functional). We should not see pain as caused by the brain alone. Pain is not felt by the brain, but by the person. ⋯ Neuroimaging investigators have argued that brain imaging may demonstrate that chronic pain is a brain disease. We argue that "disease" is a clinical concept and that conceiving of chronic pain as a brain disease can have negative consequences for research and clinical care of patients with chronic pain.
-
There is a well-established comorbidity between migraine and anxiety and depression (A/D). Here, we investigate whether this relationship is specific for migraine and A/D or whether other types of pain are also consistently associated with A/D. In addition, we test whether there is a consistent association between migraine and other types of pain when comorbidity with A/D is controlled for. Data on A/D, migraine, and 6 nonheadache pain locations (back, neck, orofacial area, abdomen, joints, and chest) were analyzed in 2,981 participants from the Netherlands Study of Depression and Anxiety (NESDA). It was tested whether the prevalence of pain in each individual location, as well as the total number of pain locations, depended on A/D and migraine status. A/D was consistently associated with pain in all measured locations. Migraine was also associated with pain in all anatomical sites, but these associations weakened substantially after correction for A/D severity, suggesting that a considerable part of the comorbidity of migraine and other types of pain may be explained by A/D. These findings emphasize the importance of accounting for A/D in studies of pain comorbidity. This will contribute to a better understanding of the mechanisms underlying A/D and pain. ⋯ Anxiety and depression are consistently associated with pain, regardless of anatomical site. These disorders may be important factors in the co-occurrence of different pain disorders. Awareness of this comorbidity and a better understanding of the underlying mechanisms may facilitate adequate treatment of both types of conditions.
-
Oxycodone hydrochloride controlled-release, also known as extended-release oxycodone (ER oxycodone), was reformulated with physicochemical barriers to crushing and dissolving intended to reduce abuse through nonoral routes of administration (ROAs) that require tampering (eg, injecting and snorting). Manufacturer shipments of original ER oxycodone (OC) stopped on August 5, 2010, and reformulated ER oxycodone (ORF) shipments started August 9, 2010. A sentinel surveillance sample of 140,496 individuals assessed for substance abuse treatment at 357 U.S. centers between June 1, 2009, and March 31, 2012, was examined for prevalence and prescription-adjusted prevalence rates of past-30-day abuse via any route, as well as abuse through oral, nonoral, and specific ROAs for ER oxycodone and comparators (ER morphine and ER oxymorphone) before and after ORF introduction. Significant reductions occurred for 8 outcome measures of ORF versus OC historically. Abuse of ORF was 41% lower (95% CI: -44 to -37) than historical abuse for OC, with oral abuse 17% lower (95% CI: -23 to -10) and nonoral abuse 66% lower (95% CI: -69 to -63). Significant reductions were not observed for comparators. Observations were consistent with the goals of a tamper resistant formulation for an opioid. Further research is needed to determine the persistence and generalizability of these findings. ⋯ This article presents preliminary findings indicating that 8 outcome measures of abuse of a reformulated ER oxycodone were lower than that for original ER oxycodone historically, particularly through nonoral ROAs that require tampering (ie, injection, snorting, smoking), in a sentinel sample of individuals assessed for substance use problems for treatment planning.