Pain
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Debate continues regarding the influence of litigation on pain outcomes after motor vehicle collision (MVC). In this study we enrolled European Americans presenting to the emergency department (ED) in the hours after MVC (n=948). Six weeks later, participants were interviewed regarding pain symptoms and asked about their participation in MVC-related litigation. ⋯ Initial pain severity in the ED predicted pain outcomes among both litigants and nonlitigants. Markers of socioeconomic disadvantage predicted worse pain outcomes in litigants but not nonlitigants, and individual pain and psychological symptoms were less predictive of pain outcomes among those engaged in litigation. These data demonstrate that persistent pain after MVC is common among those not engaged in litigation, and provide evidence for bidirectional influences between pain outcomes and litigation after MVC.
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Inflammatory and degenerative diseases of the joint are major causes of chronic pain. Long-lasting pain symptoms are thought to result from a central sensitization of nociceptive circuits. These processes include activation of microglia and spinal disinhibition. ⋯ In the spinal cord, EFX analgesia was accompanied by a reduction in microglial activation and in the levels of proinflammatory mediators. Using electrophysiological tools, we found that EFX treatment not only amplified spinal GABAergic inhibition, but also prevented prostaglandin E2-induced glycinergic disinhibition and restored a "normal" spinal pain processing. Because EFX is already distributed in several countries under the trade name of Stresam for its anxiolytic actions in humans, new clinical trials are now required to further extend its therapeutic indications as pain killer.
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Reducing the risk of chronic postoperative pain through preventive analgesia is an attractive therapeutic concept. Because peripheral nerve lesions are a major cause of chronic pain after surgery, we tested in rats whether analgesic treatment with pregabalin (PGB) has the capacity to mitigate the development of persistent neuropathic pain-like behavior. Starting on the day of spared nerve injury or 1week later, we treated rats with a continuous intrathecal infusion of PGB (300 or 900μg/24hours) or vehicle for up to 28days. ⋯ PGB did not suppress the activation of spinal microglia, indicating that analgesia alone does not eliminate certain pain mechanisms even if they depend, at least partially, on nociceptive input. Unexpectedly, intrathecal infusion of PGB did not inhibit the nerve injury-induced accumulation of its binding target, the voltage-gated calcium channel subunit α2δ1, at primary afferent terminals in the spinal cord. Interference with the synaptic trafficking of α2δ1 is not required to achieve analgesia with PGB.
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In experimental and clinical pain studies, the sex of subjects was rarely taken into account, even if nociceptive inputs appear to be processed and modulated by partially distinct neural mechanisms in each sex. In this study we analysed, in male and female mice, behavioural and neuronal responses in developing, maintaining, and recovering from neuropathic pain. Experiments were carried out in adult CD1 mice by using Chronic Constriction Injury (CCI) as neuropathic pain model. ⋯ Proteomic analysis confirmed sex-related differences of proteins associated with nerve regenerative processes. In addition, the reactive gliosis induced by CCI at day 7, as revealed by colocalization of glial fibrillary acidic protein (astrocytes) and CD11b (microglia) with phosphorylated p38, disappeared 121 days after CCI in male but not in female mice. These results may have important therapeutic implications for the treatment of neuropathic pain.
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The persistence of pain after surgery increases the recovery interval from surgery to a normal quality of life. AYX1 is a DNA-decoy drug candidate designed to prevent post-surgical pain following a single intrathecal injection. Tissue injury causes a transient activation of the transcription factor EGR1 in the dorsal root ganglia-dorsal horn network, which then triggers changes in gene expression that induce neuronal hypersensitivity. ⋯ Administered in the peri-operative period, AYX1 dose dependently prevents mechanical hypersensitivity in models of acute incisional (plantar), inflammatory (CFA), and chronic neuropathic pain (SNI) in rats. Furthermore, in a knee surgery model evaluating functional measures of postoperative pain, AYX1 improved weight-bearing incapacitance and spontaneous rearing compared to control. These data illustrate the potential clinical therapeutic benefits of AYX1 for preventing the transition of acute to chronic post-surgical pain.