Pain
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The mechanisms underlying chemotherapy-induced peripheral neuropathy have yet to be fully elucidated, but primary afferent neurons have emerged as an especially vulnerable initiating pathophysiological target. An important recent study has also shown that the initial toxicity produced by paclitaxel in patients was highly predictive of long-term outcome. In this study, we therefore focused on defining the mechanisms of acute toxicity produced by paclitaxel treatment on primary sensory neurons under in vitro conditions. ⋯ However, CCL2 applied to cultured neurons not only induced DSFs but also evoked action potentials. Evidence of oxidative stress and mitotoxicity was observed at 48 hours of exposure. These results closely parallel the responses measured in the DRG with paclitaxel exposure in vivo and so indicate that acute toxicity of paclitaxel on the DRG can be modelled using an in vitro approach.
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Youth with chronic pain and their parents face uncertainty regarding their diagnosis, treatment, and prognosis. Given the uncertain nature of chronic pain and high comorbidity of anxiety among youth, intolerance of uncertainty (IU) may be critical to the experience of pediatric chronic pain. This study longitudinally examined major tenets of the Interpersonal Fear Avoidance Model of Pain and included parent and youth IU as key factors in the model. ⋯ Youth IU had a significant indirect effect on 3-month pain interference through youth pain catastrophizing and fear of pain. The results suggest that parent and youth IU contribute to increases in youth pain interference over time through increased pain catastrophizing, parent protectiveness, and youth fear of pain. Thus, parent and youth IU play important roles as risk factors in the maintenance of pediatric chronic pain over time and may be important targets for intervention.
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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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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.