Objective To investigate the involvement of transient receptor potential vanilloid receptor 1 （TRPV1） in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation. Methods Facial infla...Objective To investigate the involvement of transient receptor potential vanilloid receptor 1 （TRPV1） in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation. Methods Facial inflammatory pain model was developed by subcutaneous injection of turpentine oil （TO） into rat facial area. Head withdrawal thermal latency （HWTL） and head withdrawal cold latency （HWCL） were measured once a day for 21 d after TO treatment using thermal and cold measurement apparatus. The immunohistochemical staining, cell-size frequency analysis and the survey of average optical density （OD） value were used to observe the changes of TRPV1 expression in the neurons of the trigeminal ganglion （TG）, peripheral nerve fibers in the vibrissal pad, and central projection processes in the trigeminal sensory nuclei caudalis （Vc） on day 3, 5, 7, 14, and 21 after TO injection. Results HWTL and HWCL decreased significantly from day 1 to day 14 after TO injection with the lowest value on day 5 and day 3, respectively, and both recovered on day 21. The number of TRPV1-labeled neurons increased remarkably from day 1 to day 14 with a peak on day 7, and returned back to the normal level on day 21. In control rats, only small and medium-sized TG neurons were immunoreactive （IR） to TRPV1, and the TRPV1-IR terminals were abundant in both the vibrissal pad and the Vc. Within 2 weeks of inflammation, the expression of TRPV1 in small and medium-sized TG neurons increased obviously. Also the TRPV1 stained terminals and fibers appeared more frequent and denser in both the vibrissal pad skin and throughout laminae Ⅰ and the outer zone of laminae Ⅱ （Ⅱo） of Vc. Conclusion Facial inflammatory pain could induce hyperalgesia to noxious heat and cold stimuli, and result in increase of the numbers of TRPV1 positive TG neurons and the peripheral and central terminals of TG. These results suggest that the phenotypic changes of TRPV1 expression in small and medium-sized TG neurons and terminals might play an important role in the development and maintenance of TO-induced inflammatory thermal hyperalgesia and cold pain sensation.展开更多
Pain is a strong symptom of diseases. Being an involuntary unpleasant feeling, it can be considered a reliable indicator of health issues. Pain has always been expressed verbally, but in some cases, traditional patien...Pain is a strong symptom of diseases. Being an involuntary unpleasant feeling, it can be considered a reliable indicator of health issues. Pain has always been expressed verbally, but in some cases, traditional patient self-reporting is not efficient. On one side, there are patients who have neurological disorders and cannot express themselves accurately, as well as patients who suddenly lose consciousness due to an abrupt faintness. On another side, medical staff working in crowded hospitals need to focus on emergencies and would opt for the automation of the task of looking after hospitalized patients during their entire stay, in order to notice any pain-related emergency. These issues can be tackled with deep learning. Knowing that pain is generally followed by spontaneous facial behaviors, facial expressions can be used as a substitute to verbal reporting, to express pain. In this paper, a convolutional neural network (CNN) model was built and trained to detect pain through patients’ facial expressions, using the UNBC-McMaster Shoulder Pain dataset. First, faces were detected from images using the Haarcascade Frontal Face Detector provided by OpenCV, and preprocessed through gray scaling, histogram equalization, face detection, image cropping, mean filtering, and normalization. Next, preprocessed images were fed into a CNN model which was built based on a modified version of the VGG16 architecture. The model was finally evaluated and fine-tuned in a continuous way based on its accuracy, which reached 92.5%.展开更多
Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory a...Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory and immune cells, and the release of neurogenic and pro-inflammatory mediators. Ultimately, endogenous analgesic mechanisms check the inflammatory response and the sensation of pain subsides. The orthodontic pain signal, once received by periodontal sensory endings, reaches the sensory cortex for pain perception through three-order neurons： the trigeminal neuron at the trigeminal ganglia, the trigeminal nucleus caudalis at the medulla oblongata and the ventroposterior nucleus at the thalamus. Many brain areas participate in the emotion, cognition and memory of orthodontic pain, including the insular cortex, amygdala, hippocampus, locus coeruleus and hypothalamus. A built-in analgesic neural pathway--periaqueductal grey and dorsal raphe---has an important role in alleviating orthodontic pain. Currently, several treatment modalities have been applied for the relief of orthodontic pain, including pharmacological, mechanical and behavioural approaches and low-level laser therapy. The effectiveness of nonsteroidal anti- inflammatory drugs for pain relief has been validated, but its effects on tooth movement are controversial. However, more studies are needed to verify the effectiveness of other modalities. Furthermore, gene therapy is a novel, viable and promising modality for alleviatin~ orthodontic oain in the future.展开更多
Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans;however,the underlying mechanisms remain largely unknown.In this study,we investigated the possible contribution of interaction b...Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans;however,the underlying mechanisms remain largely unknown.In this study,we investigated the possible contribution of interaction between ten-eleven translocation methylcytosine dioxygenase 1(TET1)and the voltage-gated K^(+)channel Kv7.2(encoded by Kcnq2)to orofacial inflammatory pain in mice.We found that complete Freund’s adjuvant(CFA)injection reduced the expression of Kcnq2/Kv7.2 in the trigeminal ganglion(TG)and induced orofacial inflammatory pain.The involvement of Kv7.2 in CFA-induced orofacial pain was further confirmed by Kv7.2 knockdown or overexpression.Moreover,TET1 knockdown in Tet1^(flox/flox)mice significantly reduced the expression of Kv7.2 and M currents in the TG and led to pain-like behaviors.Conversely,TET1 overexpression by lentivirus rescued the CFA-induced decreases of Kcnq2 and M currents and alleviated mechanical allodynia.Our data suggest that TET1 is implicated in CFA-induced trigeminal inflammatory pain by positively regulating Kv7.2 in TG neurons.展开更多
基金supported by the National Natural Science Foundation of China(No.30570629)China-Dutch Joint Research Project(No.05CDP030)
文摘Objective To investigate the involvement of transient receptor potential vanilloid receptor 1 （TRPV1） in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation. Methods Facial inflammatory pain model was developed by subcutaneous injection of turpentine oil （TO） into rat facial area. Head withdrawal thermal latency （HWTL） and head withdrawal cold latency （HWCL） were measured once a day for 21 d after TO treatment using thermal and cold measurement apparatus. The immunohistochemical staining, cell-size frequency analysis and the survey of average optical density （OD） value were used to observe the changes of TRPV1 expression in the neurons of the trigeminal ganglion （TG）, peripheral nerve fibers in the vibrissal pad, and central projection processes in the trigeminal sensory nuclei caudalis （Vc） on day 3, 5, 7, 14, and 21 after TO injection. Results HWTL and HWCL decreased significantly from day 1 to day 14 after TO injection with the lowest value on day 5 and day 3, respectively, and both recovered on day 21. The number of TRPV1-labeled neurons increased remarkably from day 1 to day 14 with a peak on day 7, and returned back to the normal level on day 21. In control rats, only small and medium-sized TG neurons were immunoreactive （IR） to TRPV1, and the TRPV1-IR terminals were abundant in both the vibrissal pad and the Vc. Within 2 weeks of inflammation, the expression of TRPV1 in small and medium-sized TG neurons increased obviously. Also the TRPV1 stained terminals and fibers appeared more frequent and denser in both the vibrissal pad skin and throughout laminae Ⅰ and the outer zone of laminae Ⅱ （Ⅱo） of Vc. Conclusion Facial inflammatory pain could induce hyperalgesia to noxious heat and cold stimuli, and result in increase of the numbers of TRPV1 positive TG neurons and the peripheral and central terminals of TG. These results suggest that the phenotypic changes of TRPV1 expression in small and medium-sized TG neurons and terminals might play an important role in the development and maintenance of TO-induced inflammatory thermal hyperalgesia and cold pain sensation.
文摘Pain is a strong symptom of diseases. Being an involuntary unpleasant feeling, it can be considered a reliable indicator of health issues. Pain has always been expressed verbally, but in some cases, traditional patient self-reporting is not efficient. On one side, there are patients who have neurological disorders and cannot express themselves accurately, as well as patients who suddenly lose consciousness due to an abrupt faintness. On another side, medical staff working in crowded hospitals need to focus on emergencies and would opt for the automation of the task of looking after hospitalized patients during their entire stay, in order to notice any pain-related emergency. These issues can be tackled with deep learning. Knowing that pain is generally followed by spontaneous facial behaviors, facial expressions can be used as a substitute to verbal reporting, to express pain. In this paper, a convolutional neural network (CNN) model was built and trained to detect pain through patients’ facial expressions, using the UNBC-McMaster Shoulder Pain dataset. First, faces were detected from images using the Haarcascade Frontal Face Detector provided by OpenCV, and preprocessed through gray scaling, histogram equalization, face detection, image cropping, mean filtering, and normalization. Next, preprocessed images were fed into a CNN model which was built based on a modified version of the VGG16 architecture. The model was finally evaluated and fine-tuned in a continuous way based on its accuracy, which reached 92.5%.
基金supported by the National Natural Science Foundation of China (81571004, 81500884 and 81400549)the Orthodontic National Key Clinical Specialty Construction Program of China, West China Hospital of Stomatology, Sichuan University
文摘Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory and immune cells, and the release of neurogenic and pro-inflammatory mediators. Ultimately, endogenous analgesic mechanisms check the inflammatory response and the sensation of pain subsides. The orthodontic pain signal, once received by periodontal sensory endings, reaches the sensory cortex for pain perception through three-order neurons： the trigeminal neuron at the trigeminal ganglia, the trigeminal nucleus caudalis at the medulla oblongata and the ventroposterior nucleus at the thalamus. Many brain areas participate in the emotion, cognition and memory of orthodontic pain, including the insular cortex, amygdala, hippocampus, locus coeruleus and hypothalamus. A built-in analgesic neural pathway--periaqueductal grey and dorsal raphe---has an important role in alleviating orthodontic pain. Currently, several treatment modalities have been applied for the relief of orthodontic pain, including pharmacological, mechanical and behavioural approaches and low-level laser therapy. The effectiveness of nonsteroidal anti- inflammatory drugs for pain relief has been validated, but its effects on tooth movement are controversial. However, more studies are needed to verify the effectiveness of other modalities. Furthermore, gene therapy is a novel, viable and promising modality for alleviatin~ orthodontic oain in the future.
基金supported by the National Natural Science Foundation of China(81771195 and 81971061)the Program for Innovative Research Team in Universities of Henan Province(22IRTSTHN028).
文摘Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans;however,the underlying mechanisms remain largely unknown.In this study,we investigated the possible contribution of interaction between ten-eleven translocation methylcytosine dioxygenase 1(TET1)and the voltage-gated K^(+)channel Kv7.2(encoded by Kcnq2)to orofacial inflammatory pain in mice.We found that complete Freund’s adjuvant(CFA)injection reduced the expression of Kcnq2/Kv7.2 in the trigeminal ganglion(TG)and induced orofacial inflammatory pain.The involvement of Kv7.2 in CFA-induced orofacial pain was further confirmed by Kv7.2 knockdown or overexpression.Moreover,TET1 knockdown in Tet1^(flox/flox)mice significantly reduced the expression of Kv7.2 and M currents in the TG and led to pain-like behaviors.Conversely,TET1 overexpression by lentivirus rescued the CFA-induced decreases of Kcnq2 and M currents and alleviated mechanical allodynia.Our data suggest that TET1 is implicated in CFA-induced trigeminal inflammatory pain by positively regulating Kv7.2 in TG neurons.
