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Many women with endometriosis continue to have pelvic pain despite optimal surgical and hormonal treatment; some also have palpable pelvic floor muscle spasm. We describe changes in pain, spasm, and disability after pelvic muscle onabotulinumtoxinA injection in women with endometriosis-associated pelvic pain, a specific population not addressed in prior pelvic pain studies on botulinum toxin.
Learn More >Acute pain is adaptive, but chronic pain is a global challenge. Many chronic pain syndromes are peripheral in origin and reflect hyperactivity of peripheral pain-signaling neurons. Current treatments are ineffective or only partially effective and in some cases can be addictive, underscoring the need for better therapies. Molecular genetic studies have now linked multiple human pain disorders to voltage-gated sodium channels, including disorders characterized by insensitivity or reduced sensitivity to pain and others characterized by exaggerated pain in response to normally innocuous stimuli. Here, we review recent developments that have enhanced our understanding of pathophysiological mechanisms in human pain and advances in targeting sodium channels in peripheral neurons for the treatment of pain using novel and existing sodium channel blockers. Expected final online publication date for the Annual Review of Neuroscience Volume 42 is July 8, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Learn More >The purpose of this study is to evaluate the effectiveness of a multimodal approach to treating chronic low back pain.
Learn More >Chronic headache is a significant worldwide problem despite advances in treatment options. Chronic headaches can have significant a detrimental impact on the activities of daily living.
Learn More >Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes.
The vicious itch-scratch cycle is a cardinal feature of atopic dermatitis (AD), in which IL-13 signaling plays a dominant role. Keratinocytes express two receptors: The heterodimeric IL-4Rα/IL-13Rα1 and IL-13Rα2. The former one transduces a functional IL-13 signal, whereas the latter IL-13Rα2 works as a nonfunctional decoy receptor. To examine whether scratch injury affects the expression of IL-4Rα, IL-13Rα1, and IL-13Rα2, we scratched confluent keratinocyte sheets and examined the expression of three IL-13 receptors using quantitative real-time PCR (qRT-PCR) and immunofluorescence techniques. Scratch injuries significantly upregulated the expression of in a scratch line number-dependent manner. Scratch-induced upregulation was synergistically enhanced in the simultaneous presence of IL-13. In contrast, scratch injuries did not alter the expression of and , even in the presence of IL-13. Scratch-induced expression was dependent on ERK1/2 and p38 MAPK signals. The expression of IL-13Rα2 protein was indeed augmented in the scratch edge area and was also overexpressed in lichenified lesional AD skin. IL-13 inhibited the expression of involucrin, an important epidermal terminal differentiation molecule. IL-13-mediated downregulation of involucrin was attenuated in IL-13Rα2-overexpressed keratinocytes, confirming the decoy function of IL-13Rα2. Our findings indicate that scratching upregulates the expression of the IL-13 decoy receptor IL-13Rα2 and counteracts IL-13 signaling.
Learn More >Pain during, and especially after, cancer remains underestimated and undertreated. Moreover, both patients and health care providers are not aware of potential benefits of rehabilitation strategies for the management of pain during and following cancer treatment. In this paper, we firstly provided a state-of-the-art overview of the best evidence rehabilitation modalities for patients having (persistent) pain during and following cancer treatment, including educational interventions, specific exercise therapies, manual therapies, general exercise therapies and mind-body exercise therapies. Secondly, the findings were summarized from a clinical perspective and discussed from a scientific perspective. In conclusion, best evidence suggests that general exercise therapy has small pain-relieving effects. Supporting evidence for mind-body exercise therapy is available only in breast cancer patients. At this moment, there is a lack of high-quality evidence to support the use of specific exercises and manual therapy at the affected region for pain relief during and after cancer treatment. No clinically relevant results were found in favor of educational interventions restricted to a biomedical approach of pain. To increase available evidence these rehabilitation modalities should be applied according to, and within, a multidisciplinary biopsychosocial pain management approach. Larger, well-designed clinical trials tailored to the origin of pain and with proper evaluation of pain-related functioning and the patient's pain experience are needed.
Learn More >We hypothesized that patients with complex regional pain syndrome (CRPS) would describe a more negative pain phenotype including higher pain severity, more neuropathic pain descriptors, more centralized pain symptoms, poorer physical function, and more affective distress when compared with patients with neuropathic pain of the extremities not meeting CRPS criteria.
Learn More >We explored the immune neuropathology underlying multi-day relief from neuropathic pain in a rat model initiated at the sciatic nerve, by using a nanoemulsion-based nanomedicine as a biological probe. The nanomedicine is theranostic: both therapeutic (containing celecoxib drug) and diagnostic (containing near-infrared fluorescent (NIRF) dye) and is small enough to be phagocytosed by circulating monocytes. We show that pain-like behavior reaches a plateau of maximum hypersensitivity 8 days post-surgery, and is the rationale for intravenous delivery at this time-point. Pain relief is evident within 24 h, lasting approximately 6 days. The ipsilateral sciatic nerve and associated L4 and L5 dorsal root ganglia (DRG) tissue of both nanomedicine and control (nanoemulsion without drug) treated animals was investigated by immunofluorescence and confocal microscopy at the peak of pain relief (day-12 post-surgery), and when pain-like hypersensitivity returns (day-18 post-surgery). At day-12, a significant reduction of infiltrating macrophages, mast cells and mast cell degranulation was observed at the sciatic nerve following treatment. In the DRG, there was no effect of treatment at both day-12 and day-18. Conversely, at the DRG, there is a significant increase in macrophage infiltration and mast cell degranulation at day-18. The treatment effect on immune pathology in the sciatic nerve was investigated further by assessing the expression of macrophage cyclooxygenase-2 (COX-2)-the drug target-and extracellular prostaglandin E2 (PGE2), as well as the proportion of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages. At day-12, there is a significant reduction of COX-2 positive macrophages, extracellular PGE2, and a striking reversal of macrophage polarity. At day-18, these measures revert to levels observed in control-treated animals. Here we present a new paradigm of immune neuropathology research, by employing a nanomedicine to target a mechanism of neuropathic pain-resulting in long-lasting pain relief–whilst revealing novel immune pathology at the injured nerve and associated DRG.
Learn More >Low back pain is the largest contributor to disability worldwide. The role of body composition as a risk factor for back pain remains unclear. Our aim was to examine the relationship between fat mass and fat distribution on back pain intensity and disability using validated tools over 3 years.
Learn More >Pain is the hallmark of sickle cell disease (SCD) and it can be severe, frequent and unpredictable. Although nociceptive pain is more common, at times, people with SCD may have neuropathic pain. The latter can occur due to peripheral or central nerve injury. This review is focused on identifying treatment of only painful sensory neuropathy in people with SCD.
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