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Migraine in children and adolescents is associated with significant disability and a high risk of persistence into adulthood.
Learn More >Discrepancies between self-reported and actigraphy sleep measures are common, producing ambiguity about which are better predictors of experimental pain outcomes. The current study tested if pain intensity during and situational pain catastrophizing following experimental pain were differentially predicted by self-reported or actigraphy sleep measures in patients with chronic temporomandibular disorder (TMJD) or healthy controls (HCs).
Learn More >Pain is the leading cause of disability in the developed world but remains a poorly treated condition. Specifically, postsurgical pain continues to be a frequent and undermanaged condition. Here, we investigate the analgesic potential of pharmacological NaV1.7 inhibition in a mouse model of acute postsurgical pain, based on incision of the plantar skin and underlying muscle of the hind paw. We demonstrate that local and systemic treatment with the selective NaV1.7 inhibitor μ-theraphotoxin-Pn3a is effectively antiallodynic in this model and completely reverses mechanical hypersensitivity in the absence of motor adverse effects. In addition, the selective NaV1.7 inhibitors ProTx-II and PF-04856264 as well as the clinical candidate CNV1014802 also reduced mechanical allodynia. Interestingly, co-administration of the opioid receptor antagonist naloxone completely reversed analgesic effects of Pn3a, indicating an involvement of endogenous opioids in the analgesic activity of Pn3a. In addition, we found superadditive antinociceptive effects of subtherapeutic Pn3a doses not only with the opioid oxycodone but also with the GABAB receptor agonist baclofen. Transcriptomic analysis of gene expression changes in dorsal root ganglia of mice after surgery did not reveal any changes in mRNA expression of endogenous opioids or opioid receptors; however, several genes involved in pain, including Runx1 (Runt related transcription factor 1), Cacna1a (CaV2.1), and Cacna1b (CaV2.2), were downregulated. In summary, these findings suggest that pain after surgery can be successfully treated with NaV1.7 inhibitors alone or in combination with baclofen or opioids, which may present a novel and safe treatment strategy for this frequent and poorly managed condition.
Learn More >Often, persistent post-traumatic headache and migraine are phenotypically similar. However, the similarities and differences in the neuropathological underpinnings of persistent post-traumatic headache and migraine require further understanding. We used diffusion tensor imaging (DTI) and a novel method for detecting subtle changes in fibertract integrity by measuring node-by-node parameters along each tract to compare fibertract profiles between those with migraine and those with persistent post-traumatic headache, and compared both cohorts to a group of controls.
Learn More >Fibromyalgia (FM) is a highly prevalent and disabling syndrome characterized by chronic widespread musculoskeletal pain and a broad range of cognitive and affective symptoms. Up to now, the pathogenesis of FM is unknown although a peripheral and central sensitization involving an imbalance on immune biomarkers appears to have a relevant role in its aetiology. The aim of this study was to extend previous clinical findings of Mindfulness-Based Stress Reduction (MBSR) to both its impact on clinical symptomatology and immune biomarkers (IL-6, CXCL8, IL-10 and hs-CRP), and also to explore the role of biomarkers as predictors of efficacy.
Learn More >Excitatory interneurons account for the majority of dorsal horn neurons, and are required for perception of normal and pathological pain. We have identified largely non-overlapping populations in laminae I-III, based on expression of substance P, gastrin-releasing peptide, neurokinin B and neurotensin. Cholecystokinin (CCK) is expressed by many dorsal horn neurons, particularly in the deeper laminae. Here we have used immunocytochemistry and in situ hybridisation to characterise the CCK cells. We show that they account for ~7% of excitatory neurons in laminae I-II, but between a third and a quarter of those in lamina III. They are largely separate from the neurokinin B, neurotensin and gastrin-releasing peptide populations, but show limited overlap with the substance P cells. Laminae II-III neurons with protein kinase Cγ (PKCγ) have been implicated in mechanical allodynia following nerve injury, and we found that around 50% of CCK cells were PKCγ-immunoreactive. Neurotensin is also expressed by PKCγ cells, and among neurons with moderate to high levels of PKCγ, ~85% expressed CCK or neurotensin. A recent transcriptomic study (Häring et al, Nat. Neurosci., 2018) identified mRNA for thyrotropin-releasing hormone (TRH) in a specific subpopulation of CCK neurons, and we show that these account for half of the CCK/PKCγ cells. These findings indicate that CCK cells are distinct from other excitatory interneuron populations that we have defined. They also show that PKCγ cells can be assigned to different classes based on neuropeptide expression, and it will be important to determine the differential contribution of these classes to neuropathic allodynia. This article is protected by copyright. All rights reserved.
Learn More >: While migraine with aura is a complex neurological syndrome with a well-characterized clinical phenotype, its pathophysiology still has grey areas which could be partially clarified by microstructural and functional neuroimaging investigations. : This article, summarizing the most significant findings from advanced neuroimaging studies, aims to achieve a unifying pathophysiological model of the migraine aura. A comprehensive review has been conducted of PubMed citations by entering the key word 'neuroimaging' combined with 'migraine with aura' AND/OR 'MRI.' Other keywords included 'grey matter' OR 'white matter', 'structural' OR 'functional'. : Converging evidence from advanced neuroimaging investigations underlined the critical role of the extrastriate visual cortex, and in particular the lingual gyrus, in the genesis of the aura phenomenon. However, the relationship between the aura and the headache phase of migraine attacks has not been completely clarified, to date, and underlying pathophysiological mechanisms need to be further elucidated.
Learn More >Heightened somatic symptoms are reported by a wide range of patients with chronic pain and have been associated with emotional distress and physical dysfunction. Despite their clinical significance, molecular mechanisms leading to their manifestation are not understood.
Learn More >The American College of Rheumatology (ACR) 2016 criteria for fibromyalgia (FM) is recommended for use in primary and referral setting. However, neither the ACR 2016 nor its predecessor ACR 2010 criteria have been validated in a referral setting. We hypothesized that the presence of higher comorbidities in the referral care setting may affect the performance of the ACR 2016. All patients referred to a tertiary care hospital with widespread pain for more than 3 months were screened using (1) the ACR 2016 criteria and (2) by a blinded expert physician (using ACR 1990 criteria). Using the ACR 1990 as reference standard, the sensitivity and specificity were calculated. Also, concomitant depression (BPHQ: Brief Patient Health Questionnaire), anxiety disorder (GAD7: Generalized Anxiety Disorder-7) and alexithymia (TAS-20: Toronto Alexithymia Scale-20) were screened for using standardized instruments. Other central sensitization syndromes were also screened clinically. Of 147 patients (132 females; median age 36 [30-45] years, median symptom duration 4 [1-6] years), 112 met the ACR 1990 criteria while 93 met the ACR 2016 criteria. There was disagreement between the two criteria in 47 patients. The sensitivity and specificity of ACR 2016 were 71% and 60%, respectively. Patients diagnosed by ACR 2016 criteria alone, had higher GAD7 scores than those diagnosed by the ACR 1990 alone. However, BPHQ and TAS-20 did not differ between the groups. Patients diagnosed by the ACR 2016 criteria had a greater odds (OR 5.2 CI 1.3-21.7, p = 0.022) of having concomitant restless leg syndrome or post-traumatic stress disorder or chronic fatigue syndrome. The sensitivity/specificity of the ACR 2016 in tertiary settings matched those found in previous primary care-based studies. Thus, the ACR 2016 criteria are valid for use in the tertiary setting. However, patients diagnosed by only the ACR 2016 criteria (and not by the ACR 1990) have high probability of having another concomitant comorbidity.
Learn More >Low back pain (LBP) is a global public health challenge, which causes high health-care costs and the highest burden on society in terms of years lived with disability. While patient expectations for improvement may have effects on LBP treatment outcomes, it remains unclear if psychological profiles modify this relationship. Therefore, the objectives of this study were to investigate if (1) patient expectations predicted short-term outcome, and (2) psychological profile, pain intensity, and self-rated health modified the relationship between expectations and outcome.
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