Pain
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Chronic pain associated with inflammation is a major clinical problem, but the underlying mechanisms are incompletely understood. Recently, we reported that GRK2(+/-) mice with a approximately 50% reduction of GRK2 develop prolonged hyperalgesia following a single intraplantar injection of the pro-inflammatory cytokine interleukin-1beta (IL-1beta). Here we show that spinal microglia/macrophage GRK2 is reduced during chronic inflammation-induced hyperalgesia. ⋯ These data establish that chronic inflammatory hyperalgesia is associated with reduced GRK2 in microglia/macrophages and that low GRK2 in these cells is sufficient to markedly prolong hyperalgesia after a single intraplantar injection of IL-1beta. Ongoing hyperalgesia is maintained by spinal microglial/macrophage activity, fractalkine signaling, p38 activation and IL-1 signaling. We propose that chronic inflammation decreases spinal microglial/macrophage GRK2, which prevents silencing of microglia/macrophage activity and thereby contributes to prolonged hyperalgesia.
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Randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are accumulating, so an updated review of the available evidence is needed. Studies were identified using MEDLINE and EMBASE searches. Numbers needed to treat (NNT) and numbers needed to harm (NNH) values were used to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions. ⋯ A large proportion of neuropathic pain patients are left with insufficient pain relief. This fact calls for other treatment options to target chronic neuropathic pain. Large-scale drug trials that aim to identify possible subgroups of patients who are likely to respond to specific drugs are needed to test the hypothesis that a mechanism-based classification may help improve treatment of the individual patients.
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Functional abdominal pain in childhood and adolescence increases risk for chronic pain in adulthood.
A few studies of long-term outcomes for pediatric functional abdominal pain (FAP) have assessed acute non-abdominal pain at follow-up, but none has assessed chronic pain. We followed a cohort of pediatric patients with FAP (n=155) and a well control group (n=45) prospectively for up to 15 years. Participants ranged in age from 18 to 32 years at a follow-up telephone interview. ⋯ One-third of the Unresolved group reported both headache and one or more sites of chronic non-abdominal pain at follow-up, compared to 17.8% of the Resolved group and 4.4% of controls. Youth with FAP that persists into adulthood may be at increased risk for chronic pain and headache. Examination of central mechanisms that are common across chronic pain disorders may enhance understanding of this subgroup of FAP.