Pain
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Alleviating chronic pain is challenging, due to lack of drugs that effectively inhibit nociceptors without off target effects on motor or central neurons. Dorsal root ganglia (DRG) contain nociceptive and non-nociceptive neurons. Drug screening on cultured DRG neurons, rather than cell lines, allows the identification of drugs most potent on nociceptors with no effects on non-nociceptors (as a proxy for unwanted side effects on CNS and motor neurons). ⋯ We confirmed the link between the oscillatory profile and nociceptors; and the slow-decay profile and non-nociceptors using three transgenic mouse lines of known pain phenotypes. We used the assay to show that blockers for Nav1.7 and Nav1.8 channels, which are validated targets for analgesics, affect non-nociceptors at concentrations needed to effectively inhibit nociceptors. However, a combination of low doses of both blockers had an additive effect on nociceptors without a significant effect on non-nociceptors, indicating that the assay can also be used to screen for combinations of existing or novel drugs for the greatest selective inhibition of nociceptors.
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Increasing numbers survive cancers in childhood and adolescence. Long-term survivors of cancers in adulthood have increased prevalence of pain and consumption of analgesics. It is not established whether long-term survivors of cancers in childhood and adolescence also have an increased use of analgesics. ⋯ For those survivors, who were persistent or high-dose users of opioids, co-medication with high doses of benzodiazepines and/or benzodiazepine-related hypnotics was far more common than among persistent and high-dose opioid users in the general population. The high prevalence of gabapentinoids may indicate increased prevalence of neuropathic pain in this group. The high degree of co-medication with benzodiazepines and/or benzodiazepine-related hypnotics in survivors on persistent and high-dose opioids might be an indication of problematic opioid use or addiction.
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It has recently been shown that epidermal growth factor receptor (EGFR) contributes to the pathogenesis of pain. We scanned genetic markers within genes coding for receptors of the EGFR family (EGFR, ERBB2, ERBB3 and ERBB4) and their ligands (AREG, BTC, EGF, EPGN, EREG, HBEGF, MUC4, NRG1, NRG2, NRG3, NRG4 and TGFA) for association with self-reported pain intensity in patients with chronic facial pain who participated in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) cohort. We found that only epiregulin (EREG) was associated with pain. ⋯ Lastly, we investigated the functional role of epiregulin using mouse models of chronic and acute pain. Injecting mice with an EREG monoclonal antibody (mAb) reversed established mechanosensitivity in the complete Freund's adjuvant (CFA) and spared nerve injury (SNI) models of chronic pain. However, the EREG mAb prolonged allodynia when administered during the development of CFA-induced mechanosensitivity and enhanced pain behavior in the capsaicin model of acute pain.
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Pain disparities based on race, sex, age, and socioeconomic status have been well documented. This study aimed to examine interactions among these sociodemographic factors on self-reported bodily pain in an urban community sample to assess whether membership in multiple at-risk groups confers greater risk for pain independent of depressive symptomatology. Participants (N=1173) were enrolled in the epidemiological Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, and reported experiences of pain in various body sites. ⋯ Among those above the poverty line, African American (AA) men were less likely to report pain than White men (p=.024) and AA women (p=.019), potentially due to greater stoicism or coping skills and sources of resilience. Consistent with prior research, significant main effects revealed that older age (OR=2.16, 95% CI[1.28, 3.64], p=.004) and higher depressive symptoms (OR=1.03, 95% CI[1.02,1.04], p<.001) were associated independently with increased likelihood of reporting pain. This study demonstrates that in an urban population intersecting sociodemographic factors create unique social identities that impact pain, and emphasizes the need for identification of relevant mediational pathways.
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Prescribers are often confronted with the decision to escalate opioid doses to achieve adequate analgesia. Understanding the impact of dose escalation on pain intensity is warranted. Using a retrospective cohort study design, Veterans with chronic pain and chronic opioid therapy were identified. ⋯ Pain scores were persistently higher among dose escalators at each 90 day time period after the index date (0-90 Days After Index Date: Dose Escalators:4.68, 95%CI: 4.64, 4.72 Dose Maintainers:4.32, 95%CI: 4.28, 4.36, p<0.0001; 91-180 Days After Index Date: Dose Escalators:4.53, 95%CI: 4.49, 4.57; Dose Maintainers:4.25, 95%CI: 4.22, 4.29, p<0.0001) but were not different in the 90 days prior to the index date (Dose Escalators:4.64, 95%CI: 4.61, 4.68; Dose Maintainers:4.59, 95%CI: 4.55, 4.63, p=0.0551). Sensitivity analyses provided similar results as the primary analyses. Opioid dose escalation among patients with chronic pain is not associated with improvements in NRS pain scores.