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Central sensitization represents a key pathophysiological mechanism underlying the development of neuropathic pain, often manifested clinically as mechanical allodynia and hyperalgesia. Adopting a mechanism-based treatment approach relies highly on the ability to assess the presence of central sensitization. The aim of the study was to investigate potential pain-autonomic readouts to operationalize experimentally induced central sensitization in the area of secondary hyperalgesia.
Learn More >We aimed to systematically assess the effectiveness and tolerability of erenumab in a clinical setting, specifically a tertiary headache center.
Learn More >In this study we aimed to evaluate the frequency of the main red flags in patients with headache who do have Covid-19.
Learn More >Chronic pain is one of the most common and interfering symptoms experienced by people with MS. There is an opportunity to shift the paradigm from interventions delivered after pain has become chronic to early, proactive interventions to alter the impact of MS-related pain. The purpose of this study was to develop and test a remotely delivered single-session group intervention to modify the pain trajectory for individuals with early MS. Research Method/Design: This was a single-center 2-group pilot randomized (1:1) controlled trial comparing a novel videoconference-delivered single-session pain intervention to a waitlist control. Participants were = 27 adults who were diagnosed with MS in the preceding 36 months and who had moderate or worse pain. The study team developed the intervention to introduce pain coping and commonly used cognitive, behavioral, and acceptance-based approaches for adaptive coping. Participants completed outcome assessments on pain intensity, interference, and coping at pretreatment, posttreatment, and 3-months posttreatment.
Learn More >Low back pain is prevalent in older populations and modifiable risk factors may include being overweight or obese. This study aimed to describe the prevalence and impact of moderate or severe low back pain in community-dwelling older adults and its association with body mass index (BMI).
Learn More >The prevalence of chronic widespread pain (CWP) in people with HIV is high, yet the underlying mechanisms are elusive. Leukocytes synthesize the endogenous opioid, β-endorphin, within their endoplasmic reticulum (ER). When released into plasma, β-endorphin dampens nociception by binding to opioid receptors on sensory neurons. We hypothesized that the heme-dependent redox signaling induces ER stress, which attenuates leukocyte β-endorphins levels/release, thereby increasing pain sensitivity in people with HIV. Results demonstrated that HIV positive individuals with CWP had increased plasma methemoglobin, erythrocytes membrane oxidation, hemolysis, and low plasma heme scavenging enzyme, hemopexin, compared to people with HIV without CWP and HIV-negative individuals with or without pain. In addition, the leukocytes from people with HIV with CWP had attenuated levels of the heme metabolizing enzyme, heme oxygenase-1, which metabolizes free heme to carbon-monoxide and biliverdin. These individuals also had elevated ER stress, and low β-endorphin in leukocytes. In vitro, heme exposure or heme oxygenase-1 deletion, decreased β-endorphins in murine monocytes/macrophages. Treating cells with a carbon-monoxide donor or an ER stress inhibitor, increased β-endorphins. To mimic hemolytic effects in a preclinical model, C57BL/6 mice were injected with phenylhydrazine hydrochloride (PHZ). PHZ increased cell-free heme and ER stress, decreased leukocyte β-endorphin levels and hindpaw mechanical sensitivity thresholds. Treatment of PHZ-injected mice with hemopexin blocked these effects, suggesting that heme-induced ER stress and a subsequent decrease in leukocyte β-endorphin is responsible for hypersensitivity in people with HIV.
Learn More >Neuroimmune-related sex differences contribute to the complexity of neurological disorders, such as drug abuse, depression, and chronic pain. The collection of articles presented in this issue add to our understanding of sex as a critical biological variable in the study of psychiatric and neurological diseases. Consideration of sex in the design and interpretation of study results is critical. Sex differences may warrant different treatment approaches for diseases in which sex or gender influences disease outcomes. The studies and reviews presented here examine the contribution of sexual dimorphism in the physiological responses and pharmacological treatments of neurological and psychiatric disorders.
Learn More >Effective treatment of neuropathic pain is challenging as its underlying mechanism remains largely unknown. Recently, the participation of brain-derived neurotrophic factor (BDNF) in neuropathic pain has been attracting increased attention. BDNF binds to a member of the tyrosine kinase receptor family, the TrkB receptor, that is specific for BDNF and is the transmembrane receptor on the posterior horn of spinal cord. In the present study, we purified two proteins that included the BDNF-binding domain of TrkB (eTrkB) and eTrkB coupled with a liposomal outer surface (liposomal eTrkB) in order to inhibit the BDNF-TrkB pathway in neuropathic pain. Results of the pull-down assay showed that eTrkB was bound to BDNF. We investigated the neuropathic pain suppression effect of this purified protein by its intrathecal administration in a rat neuropathic pain model. Mechanical and thermal hyperalgesia induced by L5 lumbar nerve ligation was markedly suppressed by treatment with eTrkB protein. Furthermore, we showed a prolonged algetic inhibition by liposomal eTrkB protein treatment. In conclusion, this study suggests that eTrkB, which sequesters endogenous BDNF and inhibits the BDNF-TrkB pathway, may prove to be a novel analgesic to treat neuropathic pain.
Learn More >Chronic pain remains challenging to both diagnose and treat. These challenges, in part, arise from limited systems-level understanding of the basic mechanisms that process nociceptive information and ultimately instantiate a subjectively available experience of pain. Here, I provide a framework, the distributed nociceptive system, for understanding nociceptive mechanisms at a systems level by integrating the concepts of neural population coding with distributed processing. Within this framework, wide-spread engagement of populations of neurons produces representations of nociceptive information that are highly resilient to disruption. The distributed nociceptive system provides a foundation for understanding complex spatial aspects of chronic pain and provides an impetus for nonpharmacological cognitive and physical therapies that can effectively target the highly distributed system that gives rise to an experience of pain.
Learn More >Many clinical and preclinical studies report higher prevalence and severity of chronic pain in females. We used hyperalgesic priming with interleukin 6 (IL-6) priming and PGE as a second stimulus as a model for pain chronicity. Intraplantar IL-6 induced hypersensitivity was similar in magnitude and duration in both males and females, while both paw and intrathecal PGE hypersensitivity was more persistent in females. This difference in PGE response was dependent on both circulating estrogen and translation regulation signaling in the spinal cord. In males, the duration of hypersensitivity was regulated by testosterone. Since the prolactin receptor (Prlr) is regulated by reproductive hormones and is female-selectively activated in sensory neurons, we evaluated whether Prlr signaling contributes to hyperalgesic priming. Using ΔPRL, a competitive Prlr antagonist, and a mouse line with ablated Prlr in the Nav1.8 sensory neuronal population, we show that Prlr in sensory neurons is necessary for the development of hyperalgesic priming in female but not male mice. Overall, sex-specific mechanisms in the initiation and maintenance of chronic pain are regulated by the neuroendocrine system and, specifically, sensory neuronal Prlr signaling.Females are more likely to experience chronic pain than males, but the mechanisms that underlie this sex difference are not completely understood. Here, we demonstrate that the duration of mechanical hypersensitivity is dependent on circulating sex hormones in mice – where estrogen caused an extension of sensitivity and testosterone was responsible for a decrease in the duration of the hyperalgesic priming model of chronic pain. Additionally, we demonstrated that Prolactin receptor expression in Nav1.8 neurons was necessary for hyperalgesic priming in female, but not male mice. Our work demonstrates a female-specific mechanism for the promotion of chronic pain involving the neuroendrocrine system and mediated by sensory neuronal prolactin receptor.
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