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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Assessing family supportive responses to pain behaviors is paramount, as these may help or hinder chronic pain (CP) adjustment. Current self-report measures of pain-specific family supportive dynamics are scarce, covering a limited range of responses. To address this gap, this paper aimed at the psychometric validation of a (revised) novel measure - the Informal Social Support for Autonomy and Dependence in Pain Inventory (ISSADI-PAIN). ⋯ The revised ISSADI-PAIN is an innovative, valid, and reliable measure of relevant functions of pain-related social support, which may influence pain persistence and adaptation. PERSPECTIVE: This article presents a novel self-report measure (ISSADI-PAIN) that assesses family support for functional autonomy and dependence in pain contexts. This measure may contribute to further research on the complexities of family supportive dynamics surrounding individuals with AP/CP, clarifying their role on pain persistence and adaptation processes.
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There have been several recent calls to re-think chronic pain in response to the growing awareness of social inequities that impact the prevalence of chronic pain and its management. This in turn has resulted in new explorations of suffering as it relates to pain. While laudable, many of these clinically oriented accounts are abstract and often fail to offer a critical theoretical understanding of social and structural inequities. ⋯ Our goal is to identify the social organization of chronic pain care which underpins experience in order to situate the social as political rather than medical or individual. PERSPECTIVE: This article explicates the health work of people living with chronic pain and marginalization, drawing on their situated experience. We offer the concept of chronic struggle as a conceptualization that allows us to bring into clear view the social organization of chronic pain in which the social is visible as political and structural rather than medical or individual.
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Recent research suggests that recovery sleep (RS) has the potential to restore pain sensitivity and modulation after hyperalgesia due to preceding sleep deprivation. However, it has not yet been systematically examined whether the restoration of these pain parameters is driven by sleep characteristics of RS. Thus, the present study assessed changes in experimental pain during RS after total sleep deprivation (TSD) to test whether RS parameters predicted the restoration of the pain system. ⋯ Thus, results indicate moderate effects of sleep manipulations on pain sensitivity, but not on pain modulation. PERSPECTIVE: This article highlights the potential of recovery sleep to let pain thresholds return to normal following their decrease after a night of total sleep deprivation. In contrast, endogenous pain modulation (temporal pain summation, conditioned pain modulation) was not affected by sleep deprivation and recovery sleep.
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Dysregulation of circular RNAs (circRNAs) has been reported to be functionally associated with chronic pain, but it is unknown whether and how circRNAs participate in visceral hypersensitivity. The expression of circKcnk9 was increased in spinal neurons of irritable bowel syndrome (IBS)-like rats. ShcircKcnk9 attenuated visceral hypersensitivity and inhibited c-Fos expression in IBS-like rats, whereas overexpression of spinal circKcnk9 induced visceral hypersensitivity and increased c-Fos expression in control rats. ⋯ Finally, the signal transducer and activator of transcription 3 (STAT3), validated as a target of miR-124-3p, could play a critical role in visceral hypersensitivity by regulating NSF/GluR2. PERSPECTIVE: Spinal circKcnk9 functions as a miR-124-3p sponge to promote visceral hypersensitivity by regulating the STAT3/NSF/GluR2 pathway. This pathway might provide a novel epigenetic mechanism of visceral hypersensitivity and a potential circRNA therapeutic target for IBS.