Pain
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Facial expressions of pain play an important role in pain diagnostics and social interactions. Given the prominent impact of sex on various aspects of pain, it is not surprising that sex differences have also been explored regarding facial expressions of pain; however, with inconclusive findings. We aim to further investigate sex differences in facial expressions of pain by using a large, combined sample to maximize statistical power. ⋯ Additionally, facial and subjective responses to pain were significantly associated across sexes, with females showing slightly stronger associations. Although variations in facial expressions of pain are very large even within each sex, our findings demonstrate that women facially communicate pain more intensively and with a better match to their subjective experience compared with men. This indicates that women might be better in using facial communication of pain in an intensity-discriminative manner.
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Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace ( http://painface.net ) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale. ⋯ By analyzing the frequency distribution of grimace scores, we found that mice spent 7x more time in a "high grimace" state following laparotomy surgery relative to sham surgery controls. Our study shows that PainFace reproducibly quantifies facial grimaces indicative of nonevoked spontaneous pain and enables laboratories to standardize and scale-up facial grimace analyses.
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Randomized Controlled Trial
The effects of virtual reality neuroscience-based therapy on clinical and neuroimaging outcomes in patients with chronic back pain: a randomized clinical trial.
Chronic pain remains poorly managed. The integration of immersive technologies (ie, virtual reality [VR]) with neuroscience-based principles may provide effective pain treatment by targeting cognitive and affective neural processes that maintain pain and therefore potentially changing neurobiological circuits associated with pain chronification and amplification. We tested the effectiveness of a novel VR neuroscience-based therapy (VRNT) to improve pain-related outcomes in n = 31 participants with chronic back pain, evaluated against usual care (waitlist control; n = 30) in a 2-arm randomized clinical trial ( NCT04468074). ⋯ Several secondary clinical outcomes were also improved by VRNT, including disability, quality of life, sleep, and fatigue. In addition, VRNT was associated with increases in dorsomedial prefrontal functional connectivity with the superior somatomotor, anterior prefrontal and visual cortices, and decreased white matter fractional anisotropy in the corpus callosum adjacent to the anterior cingulate, relative to the control condition. Thus, VRNT showed preliminary efficacy in significantly reducing pain and improving overall functioning, possibly through changes in somatosensory and prefrontal brain networks.
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Although multisite pain can markedly reduce work ability, the relevance of the bodily pain distribution as a predictor of long-term sick leave is still unknown. This study aimed to investigate the association between musculoskeletal pain distributions and long-term sick leave in the general working population of Denmark and included 66,177 currently employed wage earners without long-term sick leave during the prior 52 weeks. Participants reported whether they had pain in the lower extremity (hips/knees), upper extremity (neck/shoulders), or the low back. ⋯ Workers reporting pain in all 3 regions experienced a 72% increased risk (HR [95% CI]: 1.72 [1.55-1.91]). Thus, the number of pain regions seems to matter more than the exact pain location. The spatial extension of musculoskeletal pain in workers functions as a gradient system, where pain spread throughout the body is an independent indicator of the high risk of long-term sick leave.
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Secreted microRNAs (miRNAs) have been detected in various body fluids including the cerebrospinal fluid, yet their direct role in regulating synaptic transmission remains uncertain. We found that intrathecal injection of low dose of let-7b (1 μg) induced short-term (<24 hours) mechanical allodynia and heat hyperalgesia, a response that is compromised in Tlr7-/- or Trpa1-/- mice. Ex vivo and in vivo calcium imaging in GCaMP6-report mice revealed increased calcium signal in spinal cord afferent terminals and doral root ganglion/dorsal root ganglia neurons following spinal perfusion and intraplantar injection of let-7b. ⋯ The high dose of let-7b also induced microgliosis in the spinal cord. Of interest, intrathecal minocycline only inhibited let-7b-induced mechanical allodynia in male but not female mice. Our findings indicate that the secreted microRNA let-7b has the capacity to provoke pain through both neuronal and glial signaling, thereby establishing miRNA as an emerging neuromodulator.