Pain
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Emerging evidence suggests that perceived injustice is a risk factor for adverse outcomes associated with chronic pain. To date, however, the processes by which perceived injustice impacts on pain outcomes remain speculative. Evidence from several lines of research suggests that anger may mediate the relationship between injustice and pain outcomes. ⋯ Hierarchical regression analyses indicated that anger variables completely mediated the relationship between perceived injustice and pain intensity, and partially mediated the relationship between perceived injustice and depressive symptoms. Anger did not mediate the relationship between perceived injustice and self-reported disability. The Discussion addresses the theoretical and clinical implications of the findings.
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Chronic widespread pain (CWP) is a complex condition characterized by central hyperexcitability and altered descending control of nociception. However, nociceptive input from deep tissues is suggested to be an important drive. N-Acylethanolamines (NAEs) are endogenous lipid mediators involved in regulation of inflammation and pain. ⋯ This is the first study demonstrating that CNSP and CWP differ in levels of NAEs in response to a low-force exercise which induces pain. Increases in pain intensity as a consequence of low-force exercise were associated with low levels of PEA and SEA in CNSP and CWP. These results indicate that PEA and SEA have antinociceptive roles in humans.
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Primary and metastatic cancers that affect bone are frequently associated with severe and intractable pain. The mechanisms underlying the development of bone cancer pain are largely unknown. In this study, we first demonstrated that a functional upregulation of P2X3 receptors in dorsal root ganglion (DRG) neurons is closely associated with the neuronal hyperexcitability and the cancer-induced bone pain in MRMT-1 tumor cell-inoculated rats. ⋯ Taken together, these results suggest that functional upregulation of P2X3 receptors by VILIP-1 in DRG neurons contributes to the development of cancer-induced bone pain in MRMT-1 rats. Hence, P2X3 receptors and VILIP-1 could serve as potential targets for therapeutic interventions in cancer patients for pain management. Pharmacological blockade of P2X3 receptors or knockdown of VILIP-1 in DRGs would be used as innovative strategies for the treatment of bone cancer pain.
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Quantitative sensory testing (QST) is a psychophysical method used to quantify somatosensory function in response to controlled stimuli in healthy subjects and patients. Although QST shares similarities with the quantitative assessment of hearing or vision, which is extensively used in clinical practice and research, it has not gained a large acceptance among clinicians for many reasons, and in significant part because of the lack of information about standards for performing QST, its potential utility, and interpretation of results. A consensus meeting was convened by the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG) to formulate recommendations for conducting QST in clinical practice and research. ⋯ For the conduct of QST in healthy subjects and in patients, we recommend use of predefined standardized stimuli and instructions, validated algorithms of testing, and reference values corrected for anatomical site, age, and gender. Interpretation of results should always take into account the clinical context, and patients with language and cognitive difficulties, anxiety, or litigation should not be considered eligible for QST. When appropriate standards, as discussed here, are applied, QST can provide important and unique information about the functional status of somatosensory system, which would be complementary to already existing clinical methods.
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Randomized Controlled Trial Multicenter Study
A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to evaluate the efficacy, safety, and tolerability of naloxegol in patients with opioid-induced constipation.
Naloxegol (previously known as NKTR-118) is a peripherally acting μ-opioid receptor antagonist engineered using polymer conjugate technology in development as an oral, once-daily agent for the treatment of opioid-induced constipation (OIC). Eligible patients with OIC (n=207), defined as <3 spontaneous bowel movements (SBMs) per week with accompanying symptoms, on a stable opioid regimen of 30-1000 mg/day morphine equivalents for ≥ 2 weeks were randomized to receive 4 weeks of double-blind placebo or naloxegol (5, 25, or 50mg) once daily in sequential cohorts after a 1-week placebo run-in. The primary end point, median change from baseline in SBMs per week after week 1 of drug administration, was statistically significant for the 25- and 50-mg naloxegol cohorts vs placebo (2.9 vs 1.0 [P=0.0020] and 3.3 vs 0.5 [P=0.0001], respectively). ⋯ Similar AEs occurred with increased frequency and severity in the 50-mg cohort. There was no evidence of a statistically significant increase from baseline in pain, opioid use for the 25- and 50-mg cohorts, or centrally mediated opioid withdrawal signs and/or symptoms with naloxegol. These data demonstrate that once-daily oral naloxegol improves the frequency of SBMs compared with placebo and is generally well tolerated in this population of patients with OIC.