The journal of pain : official journal of the American Pain Society
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Given the limited options and often harmful side effects of current analgesics and the suffering caused by the opioid crisis, new classes of pain therapeutics are needed. Protease-activated receptors (PARs), particularly PAR2, are implicated in a variety of pathologies, including pain. Since the discovery of the role of PAR2 in pain, development of potent and specific antagonists has been slow. ⋯ Given the importance of this signaling pathway in PAR2-evoked nociception, C781 exemplifies a key pharmacophore for PAR2 that can be optimized for clinical development. PERSPECTIVE: Our work provides evidence that PAR2 antagonists that only block certain aspects of signaling by the receptor can be effective for blocking protease-evoked pain in mice. This is important because it creates a rationale for developing safer PAR2-targeting approaches for pain treatment.
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Randomized Controlled Trial
The effect of theta burst stimulation over the primary motor cortex on experimental hamstring pain: A randomised, controlled study.
Theta burst stimulation (TBS) over the primary motor cortex (M1) is an emerging technique that may have utility in the treatment of musculoskeletal pain. However, previous work exploring the analgesic effects of noninvasive brain stimulation has been limited largely to the arm or hand, despite 80% of acute musculoskeletal injuries occurring in the lower limb. This is a pertinent point, given the functional and neurophysiological differences between upper and lower limb musculature, as well as evidence suggesting that reorganization of corticomotor pathways is region-specific. ⋯ Subjective reports of pain intensity and function did not change following active TBS, contrasting previous reports in studies of the upper limb. PERSPECTIVE: M1 TBS reduces mechanical sensitivity associated with experimentally induced hamstring pain. Though further work is needed, these findings may hold important implications for those seeking to expedite recovery or reduce muscle sensitivity following hamstring injury.
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Oxycodone is commonly used by pregnant women for the treatment of pain. However, the potential risk associated with its use in pregnancy have not been robustly evaluated. The objective of this study was to examine neonatal outcomes associated with prenatal oxycodone exposure. ⋯ The use of oxycodone in pregnancy was not associated with an increased risk of congenital anomalies. However, oxycodone exposure was associated with a short period of gestation, preterm birth, and NAS, which likely contributed to a longer period of hospitalization following birth. PERSPECTIVE: This article assesses the neonatal risks associated with prenatal exposure to oxycodone, providing clinicians and patients with important information on the safety of oxycodone in the treatment of pain in pregnancy.
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Variability in pain-related outcomes can hamper assay sensitivity of chronic pain clinical trials. Expectations of outcome in such trials may account for some of this variability, and thereby impede development of novel pain treatments. Measurement of participants' expectations prior to initiating study treatment (active or placebo) is infrequent, variable, and often unvalidated. ⋯ We conclude with suggestions regarding future studies focused on better understanding the utility of incorporating these measures into clinical trial analyses. PERSPECTIVE: This focus article provides an overview of the relationship between participants' baseline expectations and pain-related outcomes in the setting of clinical trials of chronic pain treatments. Systematic research focused on the measurement of expectations and the impact of adjusting for expectations in clinical trial analyses may improve assay sensitivity.
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Nonpharmacological treatments are considered first-line pain management strategies, but they remain clinically underused. For years, pain-focused pragmatic clinical trials (PCTs) have generated evidence for the enhanced use of nonpharmacological interventions in routine clinical settings to help overcome implementation barriers. The Pragmatic Explanatory Continuum Indicator Summary (PRECIS-2) framework describes the degree of pragmatism across 9 key domains. ⋯ Key principles of achieving this balance include clear definitions of intervention core components, intervention monitoring and documentation that is sufficient but not overly burdensome, provider training that meets the demands of delivering an intervention in real-world settings, and use of an ethical lens to recognize and avoid potential trial futility when necessary and appropriate. PERSPECTIVE: This article presents nuances to be considered when applying the PRECIS-2 framework to describe pragmatic clinical trials. Trials must ensure that patient-centered treatment flexibility does not compromise delivery of interventions as designed, such that measurement and analysis of treatment effects is reliable.