Pain
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Randomized Controlled Trial Multicenter Study
Imipramine and Pregabalin Combination for Painful Polyneuropathy. A Randomized Controlled Trial.
Monotherapy with first-line drugs for neuropathic pain often fails to provide sufficient pain relief or has unacceptable side effects because of the need for high doses. The aim of this trial was to test whether the combination of imipramine and pregabalin in moderate doses would relieve pain more effectively than monotherapy with either of the drugs. This was a randomized, double-blind, placebo-controlled, crossover, multicenter trial consisting of four 5-week treatment periods in patients with painful polyneuropathy. ⋯ During combination therapy, the dropout rate was higher and the patients reported a higher rate and severity of side effects. Combination of moderate doses of the tricyclic antidepressant imipramine and pregabalin could be considered as an alternative to high-dosage monotherapy. However, the trial also emphasized that balance between efficacy and safety is an issue.
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Children's memories for pain play a powerful role in their pain experiences. Parents' memories may also influence children's pain experiences, by influencing parent-child interactions about pain and children's cognitions and behaviors. Pain catastrophizing of children and parents has been implicated as a factor underlying memory biases; however, this has not been empirically examined. ⋯ Although parent catastrophizing had a direct effect on pain memories, mediation analyses revealed that child catastrophizing (helplessness) indirectly influenced children's and parents' pain memories through the child's postoperative pain experience. Findings highlight that aspects of catastrophic thinking about child pain before surgery are linked to distressing pain memories several months later. Although both child and parent catastrophizing influence pain memory development, parent catastrophizing is most influential to both children's and parents' evolving cognitions about child pain.
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Protease-activated receptor type 2 (PAR2) is known to play an important role in inflammatory, visceral, and cancer-evoked pain based on studies using PAR2 knockout (PAR2(-/-)) mice. We have tested the hypothesis that specific activation of PAR2 is sufficient to induce a chronic pain state through extracellular signal-regulated kinase (ERK) signaling to protein synthesis machinery. We have further tested whether the maintenance of this chronic pain state involves a brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (trkB)/atypical protein kinase C (aPKC) signaling axis. ⋯ Systemic injection of the trkB antagonist ANA-12 similarly inhibited PAR2-mediated mechanical hypersensitivity, grimacing, and hyperalgesic priming. Inhibition of aPKC (intrathecal delivery of ZIP) or trkB (systemic administration of ANA-12) after the resolution of 2-at-induced mechanical hypersensitivity reversed the maintenance of hyperalgesic priming. Hence, PAR2 activation is sufficient to induce neuronal plasticity leading to a chronic pain state, the maintenance of which is dependent on a BDNF/trkB/aPKC signaling axis.