Pain
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Epinephrine (EPI) contributes to hyperalgesia in inflammatory and stress conditions. EPI signals via adrenoceptors, which are regulated by G protein-coupled receptor kinase 2 (GRK2). We previously reported that GRK2 is decreased in nociceptors during chronic inflammation. ⋯ In terms of EPI signalling pathways, the protein kinase A (PKA) inhibitor H-89 inhibited EPI-induced mechanical hyperalgesia in wild-type mice, whereas H-89 had no effect in mice with low GRK2 in sensory neurons (SNS-GRK2(+/-) mice). Conversely, intraplantar injection of the protein kinase Cε PKCε inhibitor TAT-PKC(εv1-2) inhibited hyperalgesia in sensory neuron specific (SNS)-GRK2(+/-) mice and not in wild-type mice. These results indicate that low GRK2 in primary sensory neurons switches EPI-induced signalling from a protein kinase A-dependent toward a PKCε-dependent pathway that ultimately mediates prolonged EPI-induced hyperalgesia.
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This study examined processes that contribute to the changing painfulness of a repeatedly presented thermal (heat) stimulus. The 3-second pulses were presented to the side of the hand at a rate of 4/min, too slow to engage wind-up. Over the course of 32 trials, pain intensity (measured by verbal report on a 0-100 scale) first declined and then (in most cases) rose again, indicating adaptation and sensitization, respectively. ⋯ Adaptation and sensitization were comparable in participants with fibromyalgia, temporomandibular disorders, and in healthy controls, indicating that these processes occur before the perceptual amplification that characterizes fibromyalgia and temporomandibular disorders. The ability of vibration to reduce pain has previously been shown to involve segmental inhibition; the finding in the present study that vibratory gating of pain is significantly (inversely) related to the rate of sensitization suggests that the latter also reflects segmental processes. Several lines of evidence thus point to the conclusion that adaptation and sensitization occur at early stages of sensory information processing.
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Randomized Controlled Trial
Cancer Health Empowerment for Living without Pain (Ca-HELP): effects of a tailored education and coaching intervention on pain and impairment.
We aimed to determine the effectiveness of a lay-administered tailored education and coaching (TEC) intervention (aimed at reducing pain misconceptions and enhancing self-efficacy for communicating with physicians) on cancer pain severity, pain-related impairment, and quality of life. Cancer patients with baseline "worst pain" of ≥4 on a 0-10 scale or at least moderate functional impairment due to pain were randomly assigned to TEC or enhanced usual care (EUC) during a telephone interview conducted in advance of a planned oncology office visit (265 patients randomized to TEC or EUC; 258 completed at least one follow-up). Patients completed questionnaires before and after the visit and were interviewed by telephone at 2, 6, and 12 weeks. ⋯ The improvement in pain-related impairment was not sustained at 6 and 12 weeks. There were no significant intervention by subgroup interactions (P>.10). We conclude that TEC, compared with EUC, resulted in improved pain communication self-efficacy and temporary improvement in pain-related impairment, but no improvement in pain severity.