Pain
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The development of nonopioid analgesics for the treatment of abdominal pain is a pressing clinical problem. To address this, we examined the expression of Gi/o-coupled receptors, which typically inhibit nociceptor activation, in colonic sensory neurons. This led to the identification of the orphan receptor GPR35 as a visceral analgesic drug target because of its marked coexpression with transient receptor potential ankyrin 1 (TRPA1), a mediator of noxious mechanotransduction in the bowel. ⋯ Consistent with this mechanism of action, we confirmed that TRPA1-mediated colonic contractions evoked by SP release were abolished by CS pretreatment in a GPR35-dependent manner. Our data demonstrate that GPR35 agonists prevent the activation and sensitisation of colonic nociceptors through the inhibition of TRPA1-mediated SP release. These findings highlight the potential of GPR35 agonists to deliver nonopioid analgesia for the treatment of abdominal pain.
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Understanding the development of chronic pain (CP) is challenging due to its multifactorial etiology. Child maltreatment (CM), encompassing various types of neglect and abuse affecting more than one-third of the population, is a critical aspect of early-life adversity with long-lasting impacts. It is increasingly recognized for its role in altering biopsychosocial processes, potentially increasing vulnerability to CP. ⋯ Importantly, biopsychosocial factors are found to explain over 60% of the association between CM and CP, with psychological factors playing a key role. This study not only characterizes the relationship between CM and CP but also underscores the influence of psychosocial elements in this dynamic interplay. These findings offer important insights into the long-term impacts of CM and provide a foundation for developing targeted therapeutic and preventive strategies for CP.
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Patients with temporomandibular disorders (TMDs) typically experience facial pain and discomfort or tenderness in the temporomandibular joint (TMJ), causing disability in daily life. Unfortunately, existing treatments for TMD are not always effective, creating a need for more advanced, mechanism-based therapies. In this study, we used in vivo GCaMP3 Ca2+ imaging of intact trigeminal ganglia (TG) to characterize functional activity of the TG neurons in vivo, specifically in mouse models of TMJ injury and inflammation. ⋯ In addition, we confirmed the attenuating effect of calcitonin gene-related peptide antagonist on FMO-induced sensitization by in vivo GCaMP3 Ca2+ imaging of intact TG. Our results contribute to unraveling the role and activity of TG neurons in the TMJ pain, bringing us closer to understanding the pathophysiological processes underlying TMJ pain after TMJ injury. Our study also illustrates the utility of in vivo GCaMP3 Ca2+ imaging of intact TG for studies aimed at developing more targeted and effective treatments for TMJ pain.
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Post-traumatic stress disorder (PTSD) is common in patients with chronic pain, adversely affects chronic pain outcomes, and is associated with opioid use and adverse opioid outcomes. Social support is a robust predictor of PTSD incidence and course as well as chronic pain outcome. We determined whether the association between PTSD and persistent opioid use was modified by emotional support in a cohort of patients receiving opioids for noncancer pain. ⋯ In fully adjusted models, PTSD was no longer associated with opioid use at 6-month follow-up among participants with high emotional support. Among those with lower emotional support, PTSD was significantly associated with opioid use at 6-month follow-up in unadjusted (odds ratio = 2.40; 95% confidence interval: 1.24-4.64) and adjusted models (odds ratio = 2.39; 95% confidence interval: 1.14-4.99). Results point to the hypothesis that improvement of emotional support in vulnerable patients with chronic pain and PTSD may help reduce sustained opioid use.
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The variability in pain drawing styles and analysis methods has raised concerns about the reliability of pain drawings as a screening tool for nonpain symptoms. In this study, a data-driven approach to pain drawing analysis has been used to enhance the reliability. The aim was to identify distinct clusters of pain patterns by using latent class analysis (LCA) on 46 predefined anatomical areas of a freehand digital pain drawing. ⋯ Statistically significant differences were found between these clusters in every self-reported health domain. Similarly, for both LBP and MBPNP, pain drawings involving more extensive pain areas were associated with higher activity limitation, more intense pain, and more psychological distress. This study presents a versatile data-driven approach for analyzing pain drawings to assist in managing spinal pain.