Pain
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Electrical stimulation of low-threshold Aβ-fibers (Aβ-ES) is used clinically to treat neuropathic pain conditions that are refractory to pharmacotherapy. However, it is unclear how Aβ-ES modulates synaptic responses to high-threshold afferent inputs (C-, Aδ-fibers) in superficial dorsal horn. Substantia gelatinosa (SG, lamina II) neurons are important for relaying and modulating converging spinal nociceptive inputs. ⋯ These findings show that activities in Aβ-fibers lead to frequency-dependent depression of synaptic transmission in SG neurons in response to peripheral noxious inputs. However, 50 Hz Aβ-ES failed to induce cell-type selective inhibition in SG neurons. The physiologic implication of this novel form of synaptic depression for pain modulation by Aβ-ES warrants further investigation.
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The goal of this study was to follow a cohort of patients undergoing total knee arthroplasty over time to: (1) identify and describe the various pain trajectories beginning preoperatively and for up to 12 months after surgery, (2) identify baseline predictors of trajectory group membership, and (3) identify trajectory groups associated with poor psychosocial outcomes 12 months after surgery. One hundred seventy-three participants (female = 85 [49%]; mean age [years] = 62.9, SD = 6.8) completed pain and psychological questionnaires and functional performance tests preoperatively and 4 days, 6 weeks, and 3 and 12 months after total knee arthroplasty. Using growth mixture modeling, results showed that a 4-group model, with a quadratic slope and baseline pain data predicting trajectory group membership, best fit the data (Akaike information criterion = 2772.27). ⋯ Group 4, the constant high pain group, comprises patients who have a neutral or positive pain slope and do not show improvement in their pain experience over the first year after surgery. This model suggests that preoperative pain levels are predictive of pain trajectory group membership and moderate preoperative pain, as opposed to low or high pain, is a risk factor for a neutral or positive pain trajectory postoperatively. Consistent with previous studies, these results show that postoperative pain is not a homogeneous condition and point to the importance of examining intraindividual pain fluctuations as they relate to pain interventions and prevention strategies.
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Treatment of neuropathic pain is a clinical challenge likely because of the time-dependent changes in many neurotransmitter systems, growth factors, ionic channels, membrane receptors, transcription factors, and recruitment of different cell types. Conversely, an increasing number of reports have shown the ability of extended and regular physical exercise in alleviating neuropathic pain throughout a wide range of mechanisms. In this study, we investigate the effect of swim exercise on molecules associated with initiation and maintenance of nerve injury-induced neuropathic pain. ⋯ Finally, prolonged swim exercise reversed astrocyte and microglia hyperactivity in the dorsal horn after nerve lesion, which remained normalized after training cessation. Together, these results demonstrate that exercise therapy induces long-lasting analgesia through various mechanisms associated with the onset and advanced stages of neuropathy. Moreover, the data support further studies to clarify whether appropriate exercise intensity, volume, and duration can also cause long-lasting pain relief in patients with neuropathic pain.
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Migraine is a common and disabling neurologic disorder, with important psychiatric comorbidities. Its pathophysiology involves activation of neurons in the trigeminocervical complex (TCC). Kainate receptors carrying the glutamate receptor subunit 5 (GluK1) are present in key brain areas involved in migraine pathophysiology. ⋯ This study demonstrates a differential role of GluK1 receptors in the TCC, antagonism of which can inhibit trigeminovascular activation through postsynaptic mechanisms. Furthermore, the data suggest a novel, possibly presynaptic, modulatory role of trigeminocervical kainate receptors in vivo. Differential activation of kainate receptors suggests unique roles for this receptor in pro- and antinociceptive mechanisms in migraine pathophysiology.