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Nerve growth factor gene therapy improves bone marrow sensory innervation and nociceptor-mediated stem cell release in a mouse model of type 1 diabetes with limb ischaemia.

Sensory neuropathy is common in people with diabetes; neuropathy can also affect the bone marrow of individuals with type 2 diabetes. However, no information exists on the state of bone marrow sensory innervation in type 1 diabetes. Sensory neurons are trophically dependent on nerve growth factor (NGF) for their survival. The aim of this investigation was twofold: (1) to determine if sensory neuropathy affects the bone marrow in a mouse model of type 1 diabetes, with consequences for stem cell liberation after tissue injury; and (2) to verify if a single systemic injection of the NGF gene exerts long-term beneficial effects on these phenomena.

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The Social and Functional Implications of High- Versus Low-Dose Opioids on Chronic Non-Cancer Pain.

Chronic non-cancer pain (CNCP) is a major health concern. Opioids may be a useful treatment option, but their use still remains controversial given the significant risks and epidemic of opioid addiction and abuse. There is limited data on whether opioid therapy is an effective treatment option for chronic non-cancer pain.

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Incident injury is strongly associated with subsequent incident temporomandibular disorder: Results from the OPPERA study.

Cross-sectional studies confirm, as expected, a positive association between jaw injury and painful temporomandibular disorders (TMDs), but prospective evaluations are lacking. We prospectively assessed incident jaw injury, injury type, and development of TMD in adults ages 18-44 years.Data were collected from 3,258 individuals from communities surrounding four U.S. academic institutes between 2006 and 2008. At enrollment, participants reported no TMD history and no facial injuries in the previous 6 months. Quarterly follow-up questionnaires assessed incident jaw injury, which was classified as intrinsic (attributed to yawning or prolonged mouth opening) or extrinsic (attributed to other causes). Examiners classified incident TMD during a median follow-up period of 2.8 years (range 0.2-5.2 years). Cox regression models used jaw injury as a time-dependent covariate to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with incident TMD.Among 1,729 participants with complete data, 175 developed TMD. Eighty percent of injuries were intrinsic. TMD annual incidence was nearly twice as high in those experiencing jaw injury (5.37%) compared to those who did not (3.44%). In the Cox model that accounted for timing of injury, the corresponding HR was 3.94 (95%CI=2.82-5.50) after adjusting for study site, age, race, and gender. Hazard ratios did not differ (p=0.91) for extrinsic injuries (HR=4.03, 95%CI=2.00-8.12) and intrinsic injuries (HR=3.85, 95%CI=2.70-5.49).Jaw injury was strongly associated with incident TMD. If surveillance and intervention following jaw injury is to be effective in preventing TMD, they should focus on both intrinsic and extrinsic injuries.

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N-3 fatty acids modulate repeated stress-evoked pain chronicity.

N-3 fatty acids, including docosahexaenoic acid (DHA), have a beneficial effect in both pain and psychiatric disorders. In fact, we previously reported that stress-induced pain prolongation might be mediated through the suppression of the G-protein coupled-receptor 40/free fatty acid receptor 1 (GPR40/FFAR1), which is activated by DHA and long-chain fatty acids. However, the involvement of GPR40/FFAR1 ligands in the development of stress-induced chronic pain has not yet been described. In this study, we investigated the role of DHA in stress-evoked pain chronicity using diet-induced n-3 fatty acid deficient mice. The n-3 fatty acid deficient mice showed exacerbation of anxiety-like behavior after repeated exposure to social defeat stress. The intact n-3 fatty acid deficient mice showed a decrease in paw threshold values. On the other hand, paw withdrawal thresholds of defeated but not non-stressed, n-3 fatty acid deficient mice continued until day 49 after paw surgery. We evaluated changes in phosphatidylcholine composition in the brains of repeat stress-evoked chronic pain model mice which were not on n-3 fatty acid deficiency diets On day 7 after paw surgery, phosphatidylcholines with DHA and other long-chain fatty acids were found to have decreased in the brains of stressed mice. Moreover, stress-induced persistent mechanical allodynia was improved by oral DHA supplementation. These results indicated that chronic stress may directly affect brain lipid composition; the related changes could be involved in chronic pain development. Our findings suggested that n-3 fatty acids, particularly DHA, are useful as a potential therapeutic target for stress-evoked chronic pain.

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Increased cerebral responses to salient transitions between alternating stimuli in chronic migraine with medication overuse headache and during migraine attacks.

In a previous study exploring central pain modulation with heterotopic stimuli in healthy volunteers, we found that transitions between sustained noxious and innocuous thermal stimulations on the foot activated the "salience matrix". Knowing that central sensory processing is abnormal in migraine, we searched in the present study for possible abnormalities of these salient transitional responses in different forms of migraine and at different time points of the migraine cycle.

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Differences in Characteristics and Comorbidity of Cluster Headache According to the Presence of Migraine.

Cluster headache (CH) can present with migrainous symptoms such as nausea, photophobia, and phonophobia. In addition, an overlap between CH and migraine has been reported. This study aimed to determine the differences in the characteristics of CH according to the presence of comorbid migraine.

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Study protocol for targeted interventions to prevent chronic low back pain in high-risk patients: A multi-site pragmatic cluster randomized controlled trial (TARGET Trial).

Low back pain (LBP) is one of the most prevalent and potentially disabling conditions for which people seek health care. Patients, providers, and payers agree that greater effort is needed to prevent acute LBP from transitioning to chronic LBP.

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How to diagnose parkinsonian central pain?

Among the different types of pain observed in Parkinson's disease, parkinsonian central pain (PCP) has the highest severity, and is poorly characterized and difficult to describe not only by patients but also by neurologists. Thus PCP remains not strictly defined and is difficult to distinguish from other types of pain on the basis of clinical description. Yet, standardizing PCP diagnosis is critical to improve the treatment of this debilitating pain subtype, but also to homogenize further studies investigating the pathophysiological mechanisms underlying this condition. Accounting for the lack of reliable validated positive clinical criteria for PCP, and as the clinical features of PCP are difficult to specify, we suggest to consider so far the gold standard diagnosis of PCP mainly based on exclusion criteria. We propose a new algorithm aiming to disentangle PCP from other chronic pain subtypes in Parkinson's disease, by sequentially ruling out what PCP is not.

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Associations between Physical Activity and Chronic Pain Severity in Youth With Chronic Abdominal Pain.

The present study aimed to: (1) better understand physical activity levels in youth with chronic abdominal pain and (2) investigate the relationship between day-level physical activity related to next day pain intensity to identify any intra-individual heterogeneity.

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Repetitive Transcranial Magnetic Stimulation at Different Frequencies for Postherpetic Neuralgia: A Double-Blind, Sham-Controlled, Randomized Trial.

Repetitive transcranial magnetic stimulation (rTMS) at 5 Hz and 10 Hz is effective in improving pain, sleep quality, and anxiety among patients with postherpetic neuralgia (PHN). But it has not been reported which frequency is more effective and which frequency is safer.

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