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Although pain is among the most common symptoms reported by patients, primary care practitioners (PCPs) face substantial challenges identifying and assessing pain.
Learn More >The hypothalamus has been suggested to be important in the initiation cascade of migraine attacks based on clinical and biochemical observations. Previous imaging studies could not disentangle the changes due to the attack and those due to the trigger compound. With a novel approach, we assessed hypothalamic neuronal activity in early premonitory phases of glyceryl-trinitrate (GTN)-induced and spontaneous migraine attacks. We measured the hypothalamic blood oxygen level-dependent (BOLD) response to oral glucose ingestion with 3T-functional MRI in 33 women, 16 with migraine without aura and 11 controls group-matched for age and BMI, on one day without prior GTN-administration, and on a second day after GTN-administration (to coincide with the premonitory phase of an induced attack). Interestingly, subgroups of patients with and without GTN-triggered attacks could be compared. Additionally, five migraineurs were investigated in a spontaneous premonitory phase. Linear mixed models were used to study between- and within-group effects. Without prior GTN-infusion, the BOLD-response to glucose was similar in migraine participants and controls (P = 0.41). After prior GTN-infusion, recovery occurred steeper and faster in migraineurs (versus day 1; P < 0.0001) and in those who developed an attack versus those who did not (P < 0.0001). Prior GTN-infusion did not alter the glucose-induced response in controls (versus baseline; P = 0.71). Just before spontaneous attacks, the BOLD-response recovery was also faster (P < 0.0001). In this study, we found new and direct evidence of altered hypothalamic neuronal function in the immediate preclinical phase of both GTN-provoked and spontaneous migraine attacks.
Learn More >Isolated injuries to the lateral cutaneous nerve (LCNC) branch of the common peroneal nerve can cause obscure chronic posterolateral knee and upper calf pain and sensory symptoms. Routine examination and electrodiagnostic testing do not detect them because the LCNC has no motor distribution and it is not interrogated by typical peroneal nerve conduction study. There are only about 10 prior cases-thus scant physician awareness-so most LCNC injuries remain misdiagnosed or undiagnosed, hindering care.
Learn More >Endometriosis is a disease of reproductive age characterized by chronic pelvic pain and infertility. Its pathogenesis is complex and still partially unexplained. However, there is increasing evidence of the role of chronic inflammation, immune system dysregulation, and oxidative stress in its development and progression. The latter appears to be involved in multiple aspects of the disease. Indeed, disease progression sustained by a hyperproliferative phenotype can be related to reactive oxygen species (ROS) imbalance, as numerous experiments using drugs to counteract hyperproliferation have shown in recent years. Chronic pelvic pain is also associated with cell function dysregulation favoring chronic inflammation and oxidative stress, specifically involving macrophages and mast cell activation. Moreover, there is increasing evidence of a role for ROS and impaired mitochondrial function not only as deleterious effectors of the ovarian reserve in patients with endometriomas but also in terms of oocyte quality and, hence, embryo development impairment. Targeting oxidative stress looks to be a promising strategy to both curb endometriotic lesion progression and alleviate endometriosis-associated symptoms of chronic pain and infertility. More investigations are nevertheless needed to develop effective therapeutic strategies for clinical application.
Learn More >Chronic orofacial pain conditions can be particularly difficult to diagnose and treat because of their complexity and limited understanding of the mechanisms underlying their aetiology and pathogenesis. Furthermore, there is considerable variability between individuals in their susceptibility to risk factors predisposing them to the development and maintenance of chronic pain as well as in their expression of chronic pain features such as allodynia, hyperalgesia and extraterritorial sensory spread. The variability suggests that genetic as well as environmental factors may contribute to the development and maintenance of chronic orofacial pain. This article reviews these features of chronic orofacial pain, and outlines findings from studies in animal models of the behavioural characteristics and underlying mechanisms related to the development and maintenance of chronic orofacial pain and trigeminal neuropathic pain in particular. The review also considers the role of environmental and especially genetic factors in these models, focussing on findings of differences between animal strains in the features and underlying mechanisms of chronic pain. These findings are not only relevant to understanding underlying mechanisms and the variability between patients in the development, expression and maintenance of chronic orofacial pain, but also underscore the importance for considering the strain of the animal to model and explore chronic orofacial pain processes.
Learn More >In 2016, the Center for Disease Control and Prevention released an opioid prescribing guideline for primary care in response to opioid overdose deaths. Despite efforts to encourage safer prescribing practices, experts and federal agencies suspect prescribing guidelines may be misapplied in clinical practice, resulting in abrupt tapering from opioid therapy. Although state laws likely influence prescriber behavior, little is known about state tapering laws. Thus, we examined the scope and variation of state tapering laws compared with federal opioid guidelines.
Learn More >Interdisciplinary pain rehabilitation (IPR) usually employs a cognitive-behavioural therapeutic (CBT) approach. However, there is growing support for chronic pain treatments based on acceptance and commitment therapy (ACT). Most studies of ACT and CBT for chronic pain have evaluated their effects after psychological interventions, not after IPR. We compared the results of an ACT-based IPR programme with two CBT-based IPR programmes.
Learn More >Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat neuropathic pain but the quality of evidence remains low. We aimed to assess the efficacy and safety of neuronavigated rTMS to the motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) in neuropathic pain over 25 weeks. We did a randomised double-blind, placebo-controlled trial at four outpatient clinics in France. Patients aged 18-75 years with peripheral neuropathic pain were randomly assigned in a 1:1 ratio to M1 or DLPFC-rTMS and re-randomised in a 2:1 ratio to active or sham rTMS (10 Hz, 3000 pulses/session, 15 sessions over 22 weeks). Patients and investigators were blind to treatment allocation. The primary endpoint was the comparison between active M1-rTMS, active DLPCF-rTMS and sham-rTMS for the change over the course of 25 weeks (group by time interaction) in average pain intensity (from 0 no pain to 10 maximal pain) on the Brief Pain Inventory (BPI), using a mixed model repeated measures analysis in patients who received at least one rTMS session (modified ITT population). Secondary outcomes included other measures of pain intensity and relief, sensory and affective dimensions of pain, quality of pain, self reported pain intensity and fatigue (patients diary), patient and clinician global impression of change (PGIC, CGIC), quality of life, sleep, mood and catastrophizing. This study is registered with ClinicalTrials.gov NCT02010281. A total of 152 patients were randomised and 149 received treatment (49 for M1; 52 for DLPFC; 48 for sham). M1-rTMS reduced pain intensity versus sham-rTMS (estimate for group x session interaction: -0.048 ± 0.02; 95% CI: -0.09 to -0.01; p = 0.01). DLPFC-rTMS was not better than sham (estimate: -0.003 ± 0.01; 95% CI:-0.04 to 0.03, p = 0.9). M1-rRMS, but not DLPFC-rTMS, was also superior to sham-rTMS on pain relief, sensory dimenson of pain, self reported pain intensity and fatigue, PGIC and CGIC. There were no effect on quality of pain, mood, sleep and quality of life as all groups improved similarly over time. Headache was the most common side effect and occurred in 17 (34.7%), 23 (44.2%) and 13 (27.1%) patients from M1, DLPFC and sham groups respectively (p = 0.2). Our results support the clinical relevance of M1-rTMS, but not of DLPFC-rTMS, for peripheral neuropathic pain with an excellent safety profile.
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