Pain
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Endometriosis affects ∼176 million women worldwide, yet on average, women experience pain ∼10 years from symptom onset before being properly diagnosed. Standard treatments (drugs or surgery) often fail to provide long-term pain relief. Elevated levels of reactive aldehydes such as 4-hydroxynonenal (4-HNE) have been implicated in the peritoneal fluid of women with endometriosis and upon accumulation, reactive aldehydes can form protein-adducts and/or generate pain. ⋯ We determined, in the eutopic and ectopic endometrium of women with severe (stage IV) peritoneal endometriosis, that ALDH2 enzyme activity was decreased, which was associated with decreased ALDH2 expression and increased 4-HNE adduct formation compared to the eutopic endometrium of controls in the proliferative phase. Using a rodent model of endometriosis and an ALDH2*2 knock-in mouse with decreased ALDH2 activity, we determined that increasing ALDH2 activity with the enzyme activator Alda-1 could prevent endometriosis lesion development as well as alleviate pain-associated behaviors in proestrus. Overall, our findings suggest that targeting the ALDH2 enzyme in endometriosis may lead to better treatment strategies and in the proliferative phase, that increased 4-HNE adduct formation within the endometrium may serve as a less invasive diagnostic biomarker to reduce years of suffering in women.
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The differentiation of chronic primary pain syndromes into those with widespread vs regional musculoskeletal pain has been characterized by controversial discussions about common or distinct mechanisms and core clinical and sensory criteria. For example, the recent revision of fibromyalgia criteria has discarded sensory characteristics such as number of "tender points." This study examined empirical evidence related to this diagnostic shift and aimed to identify basic sensory-clinical pain phenotypes in patients with chronic local primary pain (chronic primary back pain [CBP]) and patients with chronic widespread primary pain (fibromyalgia syndrome). Combined sensory-clinical pain phenotypes of 185 patients with previous CBP and fibromyalgia syndrome diagnoses were derived by a stepwise data reduction through descriptive statistical, correlational, principal components and latent class analyses. ⋯ Subsequent discriminant analysis revealed that 3 discriminant functions of pressure sensitivity markers sufficed to differentiate the clusters. These sensory-clinical phenotypes differed also in somatic symptoms and impairment but neither in psychopathology nor in psychosocial cofactors. The results highlight the relevance of sensory testing in combination with clinical pain assessment in chronic primary pain syndromes.
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Nocebo hyperalgesia refers to increases in perceived pain that putatively result from negative expectations regarding a nocebo stimulus (eg, an inert treatment, compared with no treatment). The precise cognitive-emotional factors contributing to the origins of nocebo effects are poorly understood. We aimed to test the effects of experimentally induced pain-related fear on the acquisition and extinction of nocebo hyperalgesia in healthy participants (N = 72). ⋯ However, only the High-pain group maintained significant nocebo responses at the end of extinction. Anticipatory pain-related fear induced through a threat manipulation did not amplify nocebo hyperalgesia. These findings suggest that fear of high pain may be a key contributor to the amplification of nocebo hyperalgesia, only when high pain is experienced and not when it is merely anticipated.
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Global spread of severe acute respiratory syndrome coronavirus 2 continues unabated. Binding of severe acute respiratory syndrome coronavirus 2's spike protein to host angiotensin-converting enzyme 2 triggers viral entry, but other proteins may participate, including the neuropilin-1 receptor (NRP-1). Because both spike protein and vascular endothelial growth factor-A (VEGF-A)-a pronociceptive and angiogenic factor, bind NRP-1, we tested whether spike could block VEGF-A/NRP-1 signaling. ⋯ Pronociceptive behaviors of VEGF-A were similarly blocked through suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A "silencing" of pain through subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.
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Low back pain (LBP) is a high-burden condition that lacks routine surveillance data. Health administrative data may be used for surveillance, but their validity for measuring LBP in the general population has not been established. We aimed to (1) determine the validity of health administrative data to measure LBP compared to self-reported LBP in a population-based sample of Ontario adults; and (2) describe the differences in characteristics of LBP cases based on data sources. ⋯ Characteristics of LBP cases based on data sources differed in sex, health/behaviour characteristics, and allied health care utilization. Using health administrative data significantly underestimates the prevalence of LBP. This can lead to misclassification bias that is likely nondifferential in epidemiological studies.