Pain
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We developed an animal model of activity-induced muscle pain that is dependent on local macrophage activation and release of interleukin-1β (IL-1β). Activation of purinergic type 2X (P2X) 7 receptors recruits the NOD-like receptor protein (NLRP) 3 and activates Caspase-1 to release IL-1β. We hypothesized that pharmacological blockade of P2X7, NLRP3, and Caspase-1 would prevent development of activity-induced muscle pain in vivo and release of IL-1β from macrophages in vitro. ⋯ Blockade of P2X7, NLRP3, Capsase-1, or IL-1β 24 hours, but not 1 week, after induction of the model alleviated muscle hyperalgesia in male, but not female, mice. mRNA expression of P2X7, NLRP3, Caspase-1, and IL-1β from muscle was increased 24 hours after induction of the model in both male and female mice. Using multiplex, increases in IL-1β induced by combining adenosine triphosphate with pH 6.5 in lipopolysaccharide-primed male and female macrophages were significantly lower with the presence of inhibitors of P2X7 (A740003), NLRP3 (MCC950), and Caspase-1 (Z-WEHD-FMK) when compared with the vehicle. The current data suggest the P2X7/NLRP3/Caspase-1 pathway contributed to activity-induced muscle pain initiation and early maintenance phases in male but not female, and not in late maintenance phases in male mice.
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The experience of pain is determined by many factors and has a significant impact on quality of life. This study aimed to determine sex differences in pain prevalence and intensity reported by participants with diverse disease states in several large international clinical trials. Individual participant data meta-analysis was conducted using EuroQol-5 Dimension (EQ-5D) questionnaire pain data from randomised controlled trials published between January 2000 and January 2020 and undertaken by investigators at the George Institute for Global Health. ⋯ In stratified analyses, there were differences in pain by disease group ( P for heterogeneity <0.001), but not by age group or region of recruitment. Females were more likely to report pain, and at a higher level, compared with males across diverse diseases, all ages, and geographical regions. This study reinforces the importance of reporting sex-disaggregated analysis to identify similarities and differences between females and males that reflect variable biology and may affect disease profiles and have implications for management.
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Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological modality widely used to manage pain; however, its effectiveness for individuals with fibromyalgia (FM) has been questioned. In previous studies and systematic reviews, variables related to dose of TENS application have not been considered. The objectives of this meta-analysis were (1) to determine the effect of TENS on pain in individuals with FM and (2) determine the dose-dependent effect of TENS dose parameters on pain relief in individuals with FM. ⋯ The electrode placement was not significantly associated with any effect sizes. Thus, there is evidence that TENS can effectively reduce pain in individuals with FM when applied at high or at mixed frequencies, a high intensity, or in long-term interventions involving 10 or more sessions. This review protocol was registered at PROSPERO (CRD42021252113).
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Pain is common and variable in its severity among hospitalized patients with cancer. Although biopsychosocial factors are well established as modulators of chronic pain, less is known about what patient-level factors are associated with worse pain outcomes among hospitalized cancer patients. This prospective cohort study included patients with active cancer presenting to the emergency department (ED) with pain severity of ≥4/10 and followed pain outcomes longitudinally throughout hospital admission. ⋯ Higher pain catastrophizing ( B = 0.1, P ≤ 0.001), more recent surgery ( B = -0.2, P ≤ 0.05), outpatient opioid use ( B = 1.4, P ≤ 0.001), and history of chronic pain before cancer diagnosis ( B = 0.8, P ≤ 0.05) were independently associated with greater average daily pain while admitted to the hospital. Higher pain catastrophizing ( B = 1.6, P ≤ 0.05), higher anxiety ( B = 3.7, P ≤ 0.05), lower depression ( B = -4.9, P ≤ 0.05), metastatic disease ( B = 16.2, P ≤ 0.05), and outpatient opioid use ( B = 32.8, P ≤ 0.001) were independently associated with higher daily opioid administration. Greater psychological distress, especially pain catastrophizing, as well as pain and opioid use history, predicted greater difficulty with pain management among hospitalized cancer patients, suggesting that early assessment of patient-level characteristics may help direct consultation for more intensive pharmacologic and nonpharmacologic interventions.
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Chronic pain and mental health problems have both been identified as public health emergencies and co-occur at high rates. This prospective, longitudinal investigation examined whether chronic pain status, pain-related symptoms (intensity, interference), pain catastrophizing, and insomnia severity predicted first lifetime onset of depressive and/or anxiety disorders as well as suicidality in a cohort of youth with a parental history of mood and/or anxiety disorders. Participants included 145 youth ( Mage = 13.74 years; 64% female) who completed structured diagnostic interviews at baseline and at 9- and 18-month follow-up to assess depressive and anxiety disorders as well as suicidality. ⋯ Increased pain intensity and interference at baseline predicted increased severity of suicidality at follow-up. Insomnia severity predicted increased likelihood of anxiety disorder onset. The presence of chronic pain and elevated pain-related symptoms and insomnia are premorbid risk factors for the development of significant mental health disorders and issues in youth.