Pain
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Neural mobilisations (NM) have been advocated for the treatment of nerve-related cervicobrachial pain; however, it is unclear what types of patients with nerve-related cervicobrachial pain (if any) may benefit. Medline, Web of Science, Scopus, PeDro, Cinahl, and Cochrane databases were searched from inception until December 2022. Randomised controlled trials were included if they assessed the effectiveness of NM in nerve-related cervicobrachial pain, and outcome measures were pain intensity and/or disability. ⋯ In most comparisons, there were significant differences in the effectiveness of NM between the subgroups. Neural mobilisations was consistently more effective than all alternative interventions (no treatment, traction, exercise, and standard physiotherapy alone) in 13 studies classified as Wainner cluster. PROSPERO registration: CRD42022376087.
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Neuromas are a substantial cause of morbidity and reduction in quality of life. This is not only caused by a disruption in motor and sensory function from the underlying nerve injury but also by the debilitating effects of neuropathic pain resulting from symptomatic neuromas. A wide range of surgical and therapeutic modalities have been introduced to mitigate this pain. ⋯ Therefore, there remains a great clinical need for additional therapeutic modalities to further improve treatment for patients with devastating injuries that lead to symptomatic neuromas. However, the molecular mechanisms and genetic contributions behind the regulatory programs that drive neuroma formation-as well as the resulting neuropathic pain-remain incompletely understood. Here, we review the histopathological features of symptomatic neuromas, our current understanding of the mechanisms that favor neuroma formation, and the putative contributory signals and regulatory programs that facilitate somatic pain, including neurotrophic factors, neuroinflammatory peptides, cytokines, along with transient receptor potential, and ionotropic channels that suggest possible approaches and innovations to identify novel clinical therapeutics.
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Decades of efforts in elucidating pain mechanisms, including pharmacological, neuroanatomical, and physiological studies have provided insights into how nociceptive information transmits from the periphery to the brain and the locations receiving nociceptive signals. However, little is known about which specific stimulus-dependent activated neurons, amongst heterogeneous neural environments, discriminatively evoke the cognate pain behavior. We here shed light on the population of neurons in the spinal cord activated by a painful stimulus to identify chronic pain-dependent activated neuronal subsets using Fos2A-iCreER (TRAP2) mice. ⋯ Of interest, spinal neurons expressing calretinin, calbindin, and parvalbumin were activated differently with distinct pain modalities (ie, mechanical allodynia vs heat hyperalgesia). Chemogenetic inhibition of those activated neurons significantly and specifically reduced the response to the pain stimulus associated with the stimulus modality originally given to the animals. These findings support the idea that spinal neuronal ensembles underlying nociceptive transmission undergo dynamic changes to regulate selective pain responses.
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Co-occurrence of chronic pain and clinically significant symptoms of anxiety and/or depression is regularly noted in the literature. Yet, little is known empirically about population prevalence of co-occurring symptoms, nor whether people with co-occurring symptoms constitute a distinct subpopulation within US adults living with chronic pain or US adults living with anxiety and/or depression symptoms (A/D). To address this gap, this study analyzes data from the 2019 National Health Interview Survey, a representative annual survey of self-reported health status and treatment use in the United States (n = 31,997). ⋯ The likelihood of experiencing functional limitations in daily life was highest among those experiencing co-occurring symptoms, compared with those experiencing chronic pain alone or A/D symptoms alone. Among those with co-occurring symptoms, 69.4% reported that work was limited due to a health problem, 43.7% reported difficulty doing errands alone, and 55.7% reported difficulty participating in social activities. These data point to the need for targeted investment in improving functional outcomes for the nearly 1 in 20 US adults living with co-occurring chronic pain and clinically significant A/D symptoms.
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Severe pain is often experienced by patients with head and neck cancer and is associated with a poor prognosis. Despite its frequency and severity, current treatments fail to adequately control cancer-associated pain because of our lack of mechanistic understanding. Although recent works have shed some light of the biology underlying pain in HPV-negative oral cancers, the mechanisms mediating pain in HPV+ cancers remain unknown. ⋯ Interrogation of published sequencing data of human sensory neurons exposed to human cancer-sEVs suggested a stimulation of protein translation in neurons. Induction of translation by cancer-sEVs was validated in our mouse model, and its inhibition alleviated cancer pain in mice. In summary, our work reveals that HPV+ head and neck squamous cell carcinoma-derived sEVs alter TRPV1+ neurons by promoting nascent translation to mediate cancer pain and identified several promising therapeutic targets to interfere with this pathway.