Pain
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Review Meta Analysis
Flunarizine as prophylaxis for episodic migraine: a systematic review with meta-analysis.
Based on few clinical trials, flunarizine is considered a first-line prophylactic treatment for migraine in several guidelines. In this meta-analysis, we examined the pooled evidence for its effectiveness, tolerability, and safety. Prospective randomized controlled trials of flunarizine as a prophylaxis against migraine were identified from a systematic literature search, and risk of bias was assessed for all included studies. ⋯ Meta-analyses were robust and homogenous, although several of the included trials potentially suffered from high risk of bias. Unfortunately, reporting of AEs was inconsistent and limited. In conclusion, pooled analysis of data from partially outdated trials shows that 10-mg flunarizine per day is effective and well tolerated in treating episodic migraine-supporting current guideline recommendations.
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Pediatric pain is common, and memory for it may be distressing and have long-lasting effects. Children who develop more negatively biased memories for pain (ie, recalled pain is higher than initial pain report) are at risk of worse future pain outcomes. In adolescent samples, higher child and parent catastrophic thinking about pain was associated with negatively biased memories for postsurgical pain. ⋯ Parent state anxiety and child preoperative anxiety were not associated with children's recall. Children who developed negatively biased pain memories had worse postsurgical pain several days after surgery. These findings underscore the importance of reducing parental anxiety and effective postsurgical pain management to potentially buffer against the development of negatively biased pain memories in young children.
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Chronic pain is associated with neuroplastic changes in the amygdala that may promote hyper-responsiveness to mechanical and thermal stimuli (allodynia and hyperalgesia) and/or enhance emotional and affective consequences of pain. Stress promotes dynorphin-mediated signaling at the kappa opioid receptor (KOR) in the amygdala and mechanical hypersensitivity in rodent models of functional pain. Here, we tested the hypothesis that KOR circuits in the central nucleus of the amygdala (CeA) undergo neuroplasticity in chronic neuropathic pain resulting in increased sensory and affective pain responses. ⋯ This effect was mediated through increased inhibitory postsynaptic currents, suggesting tonic disinhibition of CeA output neurons due to increased KOR activity as a possible mechanism promoting ongoing aversive aspects of neuropathic pain. Interestingly, this mechanism is not involved in SNL-induced mechanical allodynia. Kappa opioid receptor antagonists may therefore represent novel therapies for neuropathic pain by targeting aversive aspects of ongoing pain while preserving protective functions of acute pain.