Pain
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Comparative Study Clinical Trial
Developmental and sex differences in somatosensory perception--a systematic comparison of 7- versus 14-year-olds using quantitative sensory testing.
There are controversial discussions regarding developmental- and sex-related differences in somatosensory perception, which were found, eg, when comparing younger children (6-8 years), older children (9-12 years), and adolescents (13-16 years) using quantitative sensory testing (QST). The aim of our current study was to systematically assess the impact of age and sex using the QST protocol of the German Research Network on Neuropathic Pain (DFNS). QST, including thermal and mechanical detection and pain thresholds, was assessed in 86 healthy 7-year-old children (42 girls and 44 boys) and 87 healthy 14-year-old adolescents (43 girls and 44 boys). ⋯ In conclusion, developmental changes during the puberty appear to influence pain perception, whereas sex effects in childhood are negligible. At present, it is not clear what brings about the differences between adult men and women that are apparent in epidemiological studies. Our results contradict the hypothesis that differences in peripheral nerve-fiber functioning underlie sex effects.
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The management of neuropathic pain is unsatisfactory, and new treatments are required. Because the sensitivity of a subset of fast-conducting primary afferent nociceptors is thought to be regulated by the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, selectively targeting mTORC1 represents a new strategy for the control of chronic pain. Here we show that activated mTOR was expressed largely in myelinated sensory fibers in mouse and that inhibiting the mTORC1 pathway systemically alleviated mechanical hypersensitivity in mouse models of inflammatory and neuropathic pain. ⋯ Also, there was no evidence for neuronal toxicity after repeated systemic treatment with CCI-779. Additionally, we show that acute and chronic i.p. administration of Torin1 (20 mg/kg), a novel ATP-competitive inhibitor targeting both mTORC1 and mTORC2 pathways, reduced the response to mechanical and cold stimuli in neuropathic mice. Our findings emphasize the importance of the mTORC1 pathway as a regulator of nociceptor sensitivity and therefore as a potential target for therapeutic intervention, particularly in chronic pain.
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Adenosine triphosphate-sensitive potassium (K(ATP)) channels are suggested to be involved in pathogenesis of neuropathic pain, but remain underinvestigated in primary afferents and in the spinal cord. We examined alterations of K(ATP) channels in rat spinal cord and tested whether and how they could contribute to neuropathic pain. The results showed that protein expression for K(ATP) channel subunits SUR1, SUR2, and Kir6.1, but not Kir6.2, were significantly downregulated and associated with thermal hyperalgesia and mechanical allodynia after sciatic nerve injury. ⋯ Furthermore, preadministration of an astroglial gap junction decoupler carbenoxolone (10 μg) completely reversed the inhibitory effects of CRO treatment on the hyperalgesia and allodynia and phosphorylation of NR1 and NR2B receptors and the subsequent activation of Ca(2+)-dependent signals Ca(2+)/calmodulin-dependent kinase II and cyclic adenosine monophosphate (cAMP) response element binding protein. These findings suggest that nerve injury-induced downregulation of the K(ATP) channels in the spinal cord may interrupt the astroglial gap junctional function and contribute to neuropathic pain, thus the K(ATP) channels opener can reduce neuropathic pain probably partly via regulating the astroglial gap junctions. This study may provide a new strategy for treating neuropathic pain using K(ATP) channel openers in the clinic.
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Early, preemptive blockade of nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA) attenuates tumor-induced nerve sprouting and bone cancer pain. A critical unanswered question is whether late blockade of NGF/TrkA can attenuate cancer pain once NGF-induced nerve sprouting and neuroma formation has occurred. By means of a mouse model of prostate cancer-induced bone pain, anti-NGF was either administered preemptively at day 14 after tumor injection when nerve sprouting had yet to occur, or late at day 35, when extensive nerve sprouting had occurred. ⋯ In this model, as in most cancers, the individual cancer cell colonies have a limited half-life because they are constantly proliferating, metastasizing, and undergoing necrosis as the parent cancer cell colony outgrows its blood supply. Similarly, the sensory and sympathetic nerve fibers that innervate the tumor undergo sprouting at the viable/leading edge of the parent tumor, degenerate as the parent cancer cell colony becomes necrotic, and resprout in the viable, newly formed daughter cell colonies. These results suggest that preemptive or late-stage blockade of NGF/TrkA can attenuate nerve sprouting and cancer pain.
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Randomized Controlled Trial
A combined pain consultation and pain education program decreases average and current pain and decreases interference in daily life by pain in oncology outpatients: a randomized controlled trial.
Pain education programs (PEP) and pain consultations (PC) have been studied to overcome patient-related and professional-related barriers in cancer pain management. These interventions were studied separately, not in combination, and half of the studies reported a significant improvement in pain. Moreover, most PEP studies did not mention the adequacy of pain treatment. ⋯ Adequacy of pain management did not differ between the groups. Patients were more adherent to analgesics after randomization to PC-PEP than to SC (P=.03). In conclusion, PC-PEP improves pain, daily interference, and patient adherence in oncology outpatients.