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Diet-induced obesity leads to behavioral indicators of pain preceding structural joint damage in wild-type mice.

Obesity is one of the largest modifiable risk factors for the development of musculoskeletal diseases, including intervertebral disc (IVD) degeneration and back pain. Despite the clinical association, no studies have directly assessed whether diet-induced obesity accelerates IVD degeneration, back pain, or investigated the biological mediators underlying this association. In this study, we examine the effects of chronic consumption of a high-fat or high-fat/high-sugar (western) diet on the IVD, knee joint, and pain-associated outcomes.

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SPECIAL ISSUE HIV and CHRONIC PAIN (The Global Task Force for Chronic Pain in People with HIV (PWH): Developing a research agenda in an emerging field).

Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward.

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Meningeal CGRP-Prolactin interaction evokes female-specific migraine behavior.

Migraine is three times more common in women. CGRP plays a critical role in migraine pathology and causes female-specific behavioral responses upon meningeal application. These effects are likely mediated through interactions of CGRP with signaling systems specific to females. Prolactin (PRL) levels have been correlated with migraine attacks. Here, we explore a potential interaction between CGRP and PRL in the meninges.

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Baseline sleep quality, stress, and depressive symptoms, and subsequent headache occurrence in a six-week prospective cohort study of patients with episodic migraine.

Despite the high prevalence of sleep disturbance, stress, and depressive symptoms among patients with episodic migraine, there has been limited prospective research examining how these comorbid symptoms relate to future headache risk.

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Efficacy of ubrogepant based on prior exposure and response to triptans: A post hoc analysis.

To determine the potential efficacy of ubrogepant for acute treatment of migraine based on historical experience with triptans.

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Developmental innervation of cranial dura mater and migraine headache: A narrative literature review.

Migraine headache prevalence, etiology, and clinical presentations change from childhood to adulthood. Dural innervation plays a role in headache symptomatology, but the changes in innervation during development have not been fully explored in the literature.

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Prospective Association between Dysmenorrhea and Chronic Pain Development in Community-Dwelling Women.

Despite emerging evidence of associations between dysmenorrhea, enhanced pain sensitivity, and functional neuroimaging patterns consistent with chronic pain, it is unknown whether dysmenorrhea is prospectively associated with chronic pain development. Gaining a better understanding of this relationship could inform efforts in prevention of chronic pain. Using data from the national Midlife in the United States cohort, we examined the prospective association between dysmenorrhea and chronic pain development during a 10-year follow-up (starting 10 years after dysmenorrhea was measured) among 874 community-dwelling women aged 25-74 at baseline (when dysmenorrhea was measured). We fit modified Poisson regression models adjusting for sociodemographic, lifestyle and psychosocial factors. Among women who were menstruating at baseline, self-reported dysmenorrhea was associated with a 41% greater (95% confidence interval [CI] = 6%-88%) risk of developing chronic pain. Women with dysmenorrhea also developed chronic pain in more body regions (≥ 3 regions vs 1-2 regions vs none, odds ratio [OR] = 1.77, 95% CI = 1.18-2.64) and experienced greater pain interference (high-interference vs low-interference vs none, OR = 1.73, 95% CI = 1.15-2.59). Among women who had stopped menstruation at baseline, we did not find evidence of an association between their history of dysmenorrhea and subsequent risk of chronic pain development. Results suggest dysmenorrhea may be a general risk factor for chronic pain development among menstruating women. PERSPECTIVE: This study supports the temporality of dysmenorrhea and chronic pain development in a national female sample. Dysmenorrhea was also associated with developing more widespread and disabling pain among women who were still menstruating. Early management of dysmenorrhea may reduce the development and severity of chronic pain in women, although further research is required to determine whether dysmenorrhea is a causal risk factor or a risk marker of chronic pain.

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Projection-specific dopamine neurons in the ventral tegmental area participated in morphine-induced hyperalgesia and anti-nociceptive tolerance in male mice.

Long-term morphine use is associated with serious side effects, such as morphine-induced hyperalgesia and analgesic tolerance. Previous investigations have documented the association between dopamine (DA) neurons in the ventral tegmental area (VTA) and pain. However, whether VTA DA neurons are implicated in morphine-induced hyperalgesia and analgesic tolerance remains elusive.

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Derivation of dorsal spinal sensory interneurons from human pluripotent stem cells.

We describe two differentiation protocols to derive sensory spinal interneurons (INs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). In protocol 1, we use retinoic acid (RA) to induce pain, itch, and heat mediating dI4/dI6 interneurons, and in protocol 2, RA with bone morphogenetic protein 4 (RA+BMP4) is used to induce proprioceptive dI1s and mechanosensory dI3s in hPSC cultures. These protocols provide an important step toward developing therapies for regaining sensation in spinal cord injury patients. For complete details on the use and execution of this protocol, please refer to Gupta et al. (2018).

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Protocol for dissection and culture of murine dorsal root ganglia neurons to study neuropeptide release.

In this protocol, we provide step-by-step instructions for dissection and culture of primary murine dorsal root ganglia (DRG), which provide an opportunity to study the functional properties of peripheral sensory neurons . Further, we describe the analysis of neuropeptide release by ELISA as a possible downstream application. In addition, isolated DRGs can be used directly for immunofluorescence, flow cytometry, RNA sequencing or proteomic approaches, electrophysiology, and calcium imaging. For complete details on the use and execution of this protocol, please refer to Perner et al. (2020).

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