Responsiveness of the Intermittent and Constant Osteoarthritis Pain (ICOAP) scale in a trial of duloxetine for treatment of osteoarthritis knee pain.

OBJECTIVE: To assess the change in the Intermittent and Constant Osteoarthritis Pain (ICOAP)-scale scores in patients taking duloxetine or placebo and to characterize the responsiveness of the ICOAP by comparing the effect size associated with its scales to effect sizes seen with other pain scales used in this study. METHODS: This was a secondary analysis of data from a 10-week, double-blind, randomized, flexible-dose, placebo-controlled trial that enrolled patients who had persistent moderate pain due to osteoarthritis (OA) of the knee, despite having received nonsteroidal anti-inflammatory drug (NSAID) therapy. The pain measures used in this study (focusing on the drug-placebo difference at week 8) were patient-rated pain severity, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Brief Pain Inventory (BPI), and the ICOAP. RESULTS: The mean difference between duloxetine and placebo at week 8 for patient-rated pain severity, the BPI average pain, WOMAC pain, and each ICOAP scale was statistically significant (P < 0.001 for each). The ICOAP total showed a moderate effect size of 0.53, whereas the constant and intermittent scores showed effect sizes of 0.47 and 0.49, respectively. The patient-rated pain severity and the BPI average pain showed similar moderate effect sizes of 0.59 and 0.53, respectively. CONCLUSION: The study demonstrated efficacy of duloxetine compared with placebo when using the ICOAP scale in a placebo-controlled trial. The observed treatment effect size for the ICOAP scores was similar to that for other reliable, valid and responsive pain assessments. CLINICAL TRIALS REGISTRATION: ClinicalTrial.gov Identifier: NCT01018680.

Changes in expression of sensory organ-specific microRNAs in rat dorsal root ganglia in association with mechanical hypersensitivity induced by spinal nerve ligation.

Chronic neuropathic pain caused by peripheral nerve injury is associated with global changes in gene expression in damaged neurons. To understand the molecular mechanisms underlying neuropathic pain, it is essential to elucidate how nerve injury alters gene expression and how the change contributes to the development and maintenance of chronic pain. MicroRNAs are non-protein-coding RNA molecules that regulate gene expression in a wide variety of biological processes mainly at the level of translation. This study investigated the possible involvement of microRNAs in gene regulation relevant to neuropathic pain. The analyses focused on a sensory organ-specific cluster of microRNAs that includes miR-96, -182, and -183. Quantitative real-time polymerase chain reaction (qPCR) analyses confirmed that these microRNAs were highly enriched in the dorsal root ganglion (DRG) of adult rats. Using the L5 spinal nerve ligation (SNL) model of chronic neuropathic pain, we observed a significant reduction in expression of these microRNAs in injured DRG neurons compared to controls. In situ hybridization and immunohistochemical analyses revealed that these microRNAs are expressed in both myelinated (N52 positive) and unmyelinated (IB4 positive) primary afferent neurons. They also revealed that the intracellular distributions of the microRNAs in DRG neurons were dramatically altered in animals with mechanical hypersensitivity. Whereas microRNAs were uniformly distributed within the DRG soma of non-allodynic animals, they were preferentially localized to the periphery of neurons in allodynic animals. The redistribution of microRNAs was associated with changes in the distribution of the stress granule (SG) protein, T-cell intracellular antigen 1 (TIA-1). These data demonstrate that SNL induces changes in expression levels and patterns of miR-96, -182, and -183, implying their possible contribution to chronic neuropathic pain through translational regulation of pain-relevant genes. Moreover, SGs were suggested to be assembled and associated with microRNAs after SNL, which may play a role in modification of microRNA-mediated gene regulation in DRG neurons.