Pain
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The role of the major estrogen estradiol (E2) on orofacial pain conditions remains controversial with studies reporting both a pronociceptive and antinociceptive role of E2. E2 modulation of peripheral serotonergic activity may be one mechanism underlying the female prevalence of orofacial pain disorders. We recently reported that female rats in proestrus and estrus exhibit greater serotonin (5HT)-evoked orofacial nocifensive behaviors compared with diestrus and male rats. ⋯ We report that a diestrus level of E2 is protective against 5HT-evoked orofacial pain behaviors, which increase with increasing E2 concentrations, and that E2 differentially alters several pain genes in the trigeminal ganglia. Furthermore, E2 receptors coexpressed with 5HT 2A and transient receptor potential vanilloid 1 and enhanced capsaicin-evoked signaling in the trigeminal ganglia through estrogen receptor α. Overall, our data indicate that low, but not high, physiological levels of E2 protect against orofacial pain, and we provide evidence that estrogen receptor α receptor activation, but not others, contributes to sensitization of nociceptive signaling in trigeminal sensory neurons.
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This study aimed to identify patterns of opioid dispensing in Australian workers with low back pain (LBP) and determine the association of dispensing patterns with wage replacement duration. Australian workers' compensation claimants with LBP and at least 1 day of wage replacement were included. We used group-based trajectory modelling to identify opioid dispensing patterns over a two-and-a-half-year period from reported LBP onset and quantile regression to compare wage replacement duration between each dispensing pattern group. ⋯ In addition, moderate-volume and high-volume long-term dispensing groups had significantly longer wage replacement duration compared with the short-term dispensing group (median [weeks]: 126.9, 126.0, and 30.7, respectively). Without controlling for pain severity, these results offer limited evidence that opioids lead to longer wage replacement duration. Further research controlling for pain severity, psychosocial factors, and recovery expectations is required to confirm whether the relationship between opioid dispensing pattern and wage replacement duration is causal in nature.
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Long-term opioid therapy (LTOT) is associated with increased risk for depression. It is not known if the frequency of opioid use during LTOT is associated with new-onset depression. We used Optum's de-identified Integrated Claims-Clinical dataset (2010-2018) to create a cohort of 5146 patients, 18 to 80 years of age, with an encounter or claims in the year before new LTOT. ⋯ In LTOT, risk for new depression episodes is up to 40% greater in near-daily users compared with occasional users. Patients could reduce depression risk by avoiding opioid use on as many low pain days as possible. Repeated screening for depression during LTOT is warranted.
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Primary sensory neurons in dorsal root ganglia (DRG) are wrapped by satellite glial cells (SGCs), and neuron-SGC interaction may affect somatosensation, especially nociceptive transmission. P2-purinergic receptors (P2Rs) are key elements in the two-way interactions between DRG neurons and SGCs. However, because the cell types are in such close proximity, conventional approaches such as in vitro culture and electrophysiologic recordings are not adequate to investigate the physiologically relevant responses of these cells at a population level. ⋯ Blocking pannexin 1 channels attenuated the late phase response of DRG neurons, indicating that P2R stimulation may subsequently induce paracrine ATP release, which could further activate cells in the ganglion. Moreover, ganglionic α,β-MeATP treatment in vivo sensitized small neurons and enhanced responses of spinal wide-dynamic-range neurons to subsequent C-fiber inputs, suggesting that modulation via ganglionic P2R signaling could significantly affect nociceptive neuron excitability and pain transmission. Therefore, targeting functional P2Rs within ganglia may represent an important new strategy for pain modulation.
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There is moderate quality evidence that exercise can help to prevent future low back pain (LBP). This study aimed to explore patient needs and preferences for exercise programs to prevent LBP and the outcomes of these programs that would be most important to a patient. Researchers conducted 26 semistructured interviews with people with LBP. ⋯ Clinicians should discuss with patients the transition from a focus on treatment to the prevention of LBP. This provides greater opportunity to adjust goals and expectations and provide relevant education. Balancing the need for individualised care against affordability presents an ongoing challenge.