Pain
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We deployed an online pain sensitivity questionnaire (PSQ) and an at-home version of the cold pressor test (CPT) in a large genotyped cohort. We performed genome-wide association studies on the PSQ score (25,321 participants) and CPT duration (6853). ⋯ Gene-based analysis followed by pathway analysis showed that genome-wide association studies results were enriched for genes expressed in the brain and involved in neuronal development and glutamatergic synapse signaling pathways. Finally, we confirmed that females with red hair were more sensitive to pain and found that genetic variation in the MC1R gene was associated with an increase in self-perceived pain sensitivity as assessed by the PSQ.
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There is wide variation in population-level pain prevalence estimates in studies of survey data around the world. The role of country-level social, economic, and political contextual factors in explaining this variation has not been adequately examined. We estimated the prevalence of unspecified pain in adults aged 25+ years across 52 countries using data from the World Health Survey 2002 to 2004. ⋯ The model including Gender Inequality Index explained the most cross-country variance. However, even when accounting for country-level variables, some variation in pain prevalence remains, suggesting a complex interaction between personal, local, economic, and political impacts, as well as inherent differences in language, interpretations of health, and other difficult to assess cultural idiosyncrasies. The results give new insight into the high prevalence of pain around the world and its demonstrated association with macrofactors, particularly income and gender inequalities, providing justification for regarding pain as a global health priority.
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Intrathecal application of contulakin-G (CGX), a conotoxin peptide and a neurotensin analogue, has been demonstrated to be safe and potentially analgesic in humans. However, the mechanism of action for CGX analgesia is unknown. We hypothesized that spinal application of CGX produces antinociception through activation of the presynaptic neurotensin receptor (NTSR)2. ⋯ Anatomical studies demonstrated coexpression of NTSR2 and Cav2.3 in dorsal root ganglion neurons. Finally, synaptic fractionation and slice electrophysiology recordings confirmed a predominantly presynaptic effect. Together, these data reveal a nonopioid pathway engaged by a human-tested drug to produce antinociception.
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Meta Analysis
Cognitive biases among those with frequent or chronic headaches or migraines: a systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to determine the pattern of cognitive processing biases (ie, attentional, interpretation, and memory bias) towards headache and pain information observed in individuals with frequent or chronic headaches or migraines, compared with individuals without. We identified 11 studies (total N = 841). Most studies (10 of 11) assessed attentional bias. ⋯ Overall, the findings confirm an attentional bias for headache-related stimuli among people with headache, with some evidence for interpretation bias but equivocal evidence for a memory bias. For attentional biases, eye-tracking studies found evidence for biases in initial orienting. We provide suggestions for how to extend the current research to better understand cognitive biases in chronic headache.
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Meta-analysis suggests that migraine patients are no more sensitive to experimentally evoked pain than healthy control subjects. At the same time, studies have linked some migraine symptoms to quantitative sensory testing (QST) profiles. Unfortunately, previous studies associating migraine symptoms and QST have important methodological shortcomings, stemming from small sample sizes, and frequent use of univariate statistics for multivariate research questions. ⋯ Consistent with previous research, we did not observe any difference in QST ratings between migraine patients and healthy control subjects. Additionally, we found that the linear combination of symptoms related to QST was modified by the mind-body therapy enhanced mindfulness-based stress reduction (MBSR+). These results suggest that QST has a selective relationship with pain symptoms even in the absence of between-subjects differences between chronic pain patients and healthy control subjects.