Articles: chronic.
-
Neuropathic pain (NP) is a chronic condition caused by nerve injuries, such as nerve compression. Understanding its underlying neurobiological mechanisms is critical for developing effective treatments. Previous studies have shown that Kinesin family member 1A (Kif1a) heterozygous deficient mice display sensory deficits in response to nociceptive stimuli. ⋯ Furthermore, TET1 knockdown or overexpression significantly affected pain-related behaviors, as well as Kif1a methylation and transcription. Female mice given intrathecal injections of PI3K inhibitors exhibited similar molecular and behavioral outcomes as male mice. These findings offer new insights into NP mechanisms, suggesting that targeting the PI3K/KIF1A axis could be a promising therapeutic approach for NP treatment.
-
Sleep disorders that involve circadian rhythm disruption and sleep-disordered breathing (SDB) such as obstructive sleep apnea (OSA) are closely linked to respiratory infections. SDB leads to a proinflammatory state due to intermittent hypoxia, sleep fragmentation, increased oxidative stress, and elevation of inflammatory mediators such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and C-reactive protein (CRP). Furthermore, inflammatory mediator levels correlate with SDB severity, especially in people with OSA. ⋯ Chronic conditions such as bronchiectasis, with or without concomitant cystic fibrosis, can lead to structural sleep changes and increase the risk of OSA due to chronic cough, arousals, aspirations, hypoxia, upper airway edema, and overexpression of proinflammatory cytokines. The protective effect of treatment for sleep disorders against respiratory infection is currently unknown. However, in people presenting with respiratory infection, it is important to test for SDB to prevent complications.
-
Exosomes served as "communicators" to exchange information among different cells in the nervous system. Our previous study demonstrated that the enhanced spinal synaptic transmission contributed to chronic visceral pain in irritable bowel syndrome. However, the underlying mechanism of primary sensory neuron (PSN)-derived exosomes on spinal transmission remains unclear. ⋯ The PSN-derived exosomal miR-1306-3p sorted from spinal dorsal horn activated P2X3R, enhanced spinal synaptic transmission, and led to visceral pain in NMD mice. Moreover, upregulation of Rab27a in dorsal root ganglia mediated the increased release of PSN-derived exosomes, and intrathecal injection of siR-Rab27a reduced visible PSN-derived exosomes in spinal cord, suppressed spinal synaptic transmission, and alleviated visceral pain in NMD mice. This and future studies would reveal the detailed mechanisms of PSN-derived exosomes and provide a potential target for clinical treatment of chronic visceral pain in patients with irritable bowel syndrome.
-
Chronic musculoskeletal pain (CMP) causes significant health loss worldwide and is one of the major public health issues of our time. Cigarette smoking is an independent risk factor of CMP. The present study examined the potential mediating role of 2 subproducts of cigarette smoke, acrylamide and cadmium, individually and combined, on the association between cigarette smoking and CMP, using the Inverse Odds Ratio Weighting (IORW) method. ⋯ Small indirect effects were identified through acrylamide (aOR = 1.24 [95% CI: 0.96-1.61]) and cadmium (aOR = 1.56 [95% CI: 0.92-2.63]) only among moderate and heavy smokers. When both biomarkers were considered together, their indirect effect was larger (aOR = 2.07 [95% CI: 1.32-3.23]). These results suggest that the association between cigarette smoking and CMP is mediated by acrylamide and cadmium and that these substances, also present in food and the environment, may serve as biomarkers of CMP.