Pain
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Existing analgesics are not efficacious in treating all patients with chronic pain and have harmful side effects when used long term. A deeper understanding of pain signaling and sensitization could lead to the development of more efficacious analgesics. Nociceptor sensitization occurs under conditions of inflammation and nerve injury where diverse chemicals are released and signal through receptors to reduce the activation threshold of ion channels, leading to an overall increase in neuronal excitability. ⋯ Thus, PIP2 sits at a critical convergence point for multiple receptors, ion channels, and signaling pathways that promote and maintain chronic pain. Decreasing the amount of PIP2 in neurons was recently shown to attenuate pronociceptive signaling and could provide a novel approach for treating pain. Here, we review the lipid kinases that are known to regulate pain signaling and sensitization and speculate on which additional lipid kinases might regulate signaling in nociceptive neurons.
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Much evidence from pain patients and animal models shows that chronic pain does not exist in a vacuum but has varied comorbidities and far-reaching consequences. Patients with long-term pain often develop anxiety and depression and can manifest changes in cognitive functioning, particularly with working memory. Longitudinal studies in rodent models also show the development of anxiety-like behavior and cognitive changes weeks to months after an injury causing long-term pain. ⋯ Nevertheless, studies in humans reveal that lifestyle choices, such as the practice of meditation or yoga, can reduce pain perception and have the opposite effect on the brain as does chronic pain. In rodent models, studies show that physical activity and a socially enriched environment reduce pain behavior and normalize brain function. Together, these studies suggest that the burden of chronic pain can be reduced by nonpharmacological interventions.
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Concussion after a force to the head is called mild traumatic brain injury (mTBI). Approximately 1 in 5 patients with mTBI will develop chronic pain (headache and widespread pain, possibly of central origin) and/or sleep problems (insomnia, disordered breathing, periodic limb movements). However, the predisposing mechanisms for chronic pain in patients with mTBI are unknown. ⋯ Customized approaches are indicated for mTBI, pain, and sleep complaints. Further studies in pediatric, sport, and transportation populations are needed to prevent TBI chronification. Improvements are emerging in biomarker sensitivity and specificity and management strategies for TBI, pain, and sleep comorbidities.
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Cancer pain sends a message. It is frightening to the patient. It heralds progression or recurrence to the oncologist. ⋯ In this manner, these nerves serve as bellwethers and sensors embedded within the cancer. When we rigorously assess patients' cancer pain, we gain insight into the action of cancer. An enhanced understanding of cancer pain offers biological questions that if answered might not only provide relief from cancer pain but might also improve survival.
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Multicenter Study
Predictors of New Onset Distal Neuropathic Pain in HIV-infected Individuals in the Era of Combination Antiretroviral Therapy.
Despite modern combination antiretroviral therapy, distal neuropathic pain (DNP) continues to affect many individuals with HIV infection. We evaluated risk factors for new-onset DNP in the CNS Antiretroviral Therapy Effects Research (CHARTER) study, an observational cohort. Standardized, semiannual clinical evaluations were administered at 6 US sites. ⋯ During follow-up, more severe depression symptoms conferred a significantly elevated risk. The associations with opioid use disorders and depression reinforce the view that the clinical expression of neuropathic pain with peripheral nerve disease is strongly influenced by neuropsychiatric factors. Delineating such risk factors might help target emerging preventive strategies, for example, to individuals with a history of opioid use disorder, or might lead to new treatment approaches such as the use of tools to ameliorate depressed mood.