Despite its clinical importance, the underlying central mechanisms of pruritic behaviors are poorly understood. To investigate the role of nociceptive arcuate nucleus neurons in chloro-quine-induced pruritic behaviors...Despite its clinical importance, the underlying central mechanisms of pruritic behaviors are poorly understood. To investigate the role of nociceptive arcuate nucleus neurons in chloro-quine-induced pruritic behaviors in mice, we tested the effect of arcuate nucleus neurons and interscapular brown adipose tissue (IBAT) on itch produced by intradermal injection of chloroquine in the nape of the neck. Our results provide several lines of evidence for an important role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behavior: (1) Intradermal microinjection of chloro-quine resulted in a dramatic increase in itch behaviors accompanied by the activation of c-Fos positive neurons in arcuate nucleus; (2) Microinjection of chloroquine significantly increased IBAT temperature in the mice. These findings suggested that chloroquine-induced pruritic behaviors were associated with the activity of nociceptive arcuate nucleus neurons.展开更多
μ-opioid receptor （MOR） agonists such as morphine are powerful analgesics used for pain therapy. However, the use of these drugs is limited by their side-effects, which include antinociceptive tolerance and depende...μ-opioid receptor （MOR） agonists such as morphine are powerful analgesics used for pain therapy. However, the use of these drugs is limited by their side-effects, which include antinociceptive tolerance and dependence. Earlier studies reported that MOR analgesic tolerance is reduced by blockade of 5-opioid receptors （DORs） that interact with MORs. Recent studies show that the MOR/DOR interaction in nociceptive afferent neurons in the dorsal root ganglion may contribute to morphine analgesic tolerance. Further analysis of the mechanisms for regulating the trafficking of receptors, ion channels and signaling molecules in nociceptive afferent neurons would help to understand the nociceptive mechanisms and improve pain therapy.展开更多
Objective: This study was done to determine whether Tualang honey could prevent the altered nociceptive behaviour, with its associated changes of oxidative stress markers and morphology of the spinal cord,among the of...Objective: This study was done to determine whether Tualang honey could prevent the altered nociceptive behaviour, with its associated changes of oxidative stress markers and morphology of the spinal cord,among the offspring of prenatally stressed rats.Methods: Pregnant rats were divided into three groups: control, stress, and stress treated with Tualang honey. The stress and stress treated with Tualang honey groups were subjected to restraint stress from day 11 of pregnancy until delivery. Ten week old male offspring(n = 9 from each group) were given formalin injection and their nociceptive behaviours were recorded. After 2 h, the rats were sacrificed, and their spinal cords were removed to assess oxidative stress activity and morphology. Nociceptive behaviour was analysed using repeated measures analysis of variance(ANOVA), while the levels of oxidative stress parameters and number of Nissl-stained neurons were analysed using a one-way ANOVA.Results: This study demonstrated that prenatal stress was associated with increased nociceptive behaviour, changes in the oxidative stress parameters and morphology of the spinal cord of offspring exposed to prenatal stress; administration of Tualang honey reduced the alteration of these parameters.Conclusion: This study provides a preliminary understanding of the beneficial effects of Tualang honey against the changes in oxidative stress and neuronal damage in the spinal cord of the offspring of prenatally stressed rats.展开更多
BACKGROUND： Previous morphological studies have demonstrated that group Ⅲ metabotropic glutamate receptors （mGluRs） are commonly found in nociceptive pathways, particularly in the terminals of primary afferent fib...BACKGROUND： Previous morphological studies have demonstrated that group Ⅲ metabotropic glutamate receptors （mGluRs） are commonly found in nociceptive pathways, particularly in the terminals of primary afferent fibers in the spinal dorsal horn. OBJECTIVE： To investigate the role of group Ⅲ mGluRs in a rat model of spinal nociception by intrathecal administration of a selective agonist, L-Serine-O-phosphate （L-SOP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment. The study was performed at the Department of Physiology and Neurobiology, Shanxi Medical University, between March 2007 and May 2008. MATERIALS： L-SOP of group Ⅲ mGluRs （Tocris Cookson Ltd, UK）, formalin （Sigma, USA）, rabbit anti-c-Fos polyclonal antibody and biotin-labeled goat anti-rabbit IgG （Cell Signaling Technology, USA） were used in this study. METHODS： A total of 26 healthy Wistar rats, aged 1 month and weighing 100-120 g, were subjected to intrathecal catheter implantation. After 5-8 days, 10 rats were selected according to experimental requirements. L-SOP 250 nmol in 10 μL, or the equivalent volume of normal saline, was administered by intrathecal injection into the L3-5 region of the spinal cord in the experimental and control groups, respectively. After 15 minutes, formalin （5%, 50 μL） was subcutaneously injected into the plantar of the left hindpaw of each rat to establish formalin-induced pain models. MAIN OUTCOME MEASURES： Nociceptive behavioral responses and immunohistochemical examination of Fos expression. RESULTS： Intrathecal injection of L-SOP significantly attenuated the second phase nociceptive response compared with the control group （P 〈 0.05）, and Fos expression in the spinal dorsal horn was significantly decreased along with the number of Fos-like immunoreactive neurons （P 〈 0.05）. CONCLUSION： Group Ⅲ mGluRs are involved in the modulation of nociceptive signals, and their activation suppresses the transmission of nociceptive signals.展开更多
Experiments were performed on 25 rats. Putative serotonergic antagonist, Cyproheptadine(Cyp), was applied microiontophoretically on the nucleus parafascicularis of the thalamus (Pf) andthe effect of Cyp on Pf nocicept...Experiments were performed on 25 rats. Putative serotonergic antagonist, Cyproheptadine(Cyp), was applied microiontophoretically on the nucleus parafascicularis of the thalamus (Pf) andthe effect of Cyp on Pf nociceptive neuronal discharge was observed. The result suggested that Cypcan increase the spontaneous and evoked discharge rates of Pf nociceptive neuron, and that Cypmay antagonize the inhibitory effect of endogenous serotonin on the spontaneous and evokeddischarges of Pf nociceptive neurons.展开更多
Background: Cardiac pain arising from acute coronary syndrome (ACS) is a multi-factorial phenomenon. Historically, episodes of cardiac pain have been captured using a one-dimensional numeric pain rating scale. Lacking...Background: Cardiac pain arising from acute coronary syndrome (ACS) is a multi-factorial phenomenon. Historically, episodes of cardiac pain have been captured using a one-dimensional numeric pain rating scale. Lacking in clinical practice are acute pain assessments that employ a comprehensive evaluation of an emergent ACS episode. Aim: To examine the sensory-discriminative, motivational-affective and cognitive-evaluative dimensions of ACS-related pain. Methods: A descriptive-correlational, repeated-measure design was used to collect data on 121 ACS patients of their cardiac pain intensity. The (numeric rating scale-NRS 0-10 scale) measured chest pain “Now” and “Worst pain in the previous 2 hours over 8 hours” and the McGill Pain Questionnaire Short-Form (MPQ-SF) measured pain at 4 hours. Results: Mean age was 67.6 ± 13, 50% were male, 60% had unstable angina and 40% had Non-ST-elevation myocardial infarction. Cardiac pain intensity scores remained in the mild range from 1.1 ± 2.2 to 2.4 ± 2.7. MPQ-SF: 66% described pain as distressing and 26% reported pain was horrible or excruciating. Participants described ACS pain quality as acute injury (nociceptive pain: heavy, cramping, stabbing), as nerve damage (neuropathic: gnawing, hot-burning, shooting) and as a mixture of acute and chronic pain qualities (aching, tender and throbbing). Conclusions: Patients reported both nociceptive and neuropathic cardiac pain. It is unclear if pain perceptions are due to: i) pathophysiology of clot formation, ii) occurrence of a first or repeated ACS episode, or iii) complex co-morbidities. Pain arising from ACS requires an understanding of the interplay of ischemic, metabolic and neuropathophysiological mechanisms that contribute to complex cardiac pain experiences.展开更多
Bradykinin is an inflammatory mediator and one of the most potent endogenous pain-inducing substances. When released at the site of tissue damage or inflammation
As a main structure of the limbic system,the hippocampus plays a critical role in pain perception and chronicity.The ventral hippocampal CA1(vCA1)is closely associated with negative emotions such as anxiety,stress,and...As a main structure of the limbic system,the hippocampus plays a critical role in pain perception and chronicity.The ventral hippocampal CA1(vCA1)is closely associated with negative emotions such as anxiety,stress,and fear,yet how vCA1 neurons encode nociceptive information remains unclear.Using in vivo electrophysiological recording,we characterized vCA1 pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli and were implicated in encoding stimuli modalities in naïve rats.Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions:the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli,whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties.Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors.Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats,whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain.These results provide direct evidence for the representations of nociceptive information in vCA1.展开更多
Aim: Repeated microinjections of non-opioid an-algesics into the midbrain periaqueductal gray matter and rostral ventro-medial medulla induce antinociception with development of tolerance. Antinociception following sy...Aim: Repeated microinjections of non-opioid an-algesics into the midbrain periaqueductal gray matter and rostral ventro-medial medulla induce antinociception with development of tolerance. Antinociception following systemic administra-tion of non-steroidal anti-inflammatory drugs (N SAIDs) also exhibit tolerance. Presently our aim was to investigate the development of tolerance to the antinociceptive effects of NSAIDs analgine, ketorolac, and xefocam microinjected into cen-tral nucleus of amygdala (Ce) in rats. Methods: Under anesthesia with thiopental a stainless steel guide cannula was stereotaxically implanted uni- laterally or bilaterally into the Ce using stereo-taxic atlas coordinates, and anchored to the cra- nium by dental cement. Five days after surgery, 3 μl of these NSAIDs were injected via the injec-tion cannula while the rat was gently restrained. Twenty min post microinjection, i.e. 10-min be-fore the peak of the drugs’ effect is normally rea- ched, animals were tested with tail flick (TF) and hot plate (HP) tests. On the 5th experimental day all animals received a Ce microinjection of mor-phine. Results: Daily microinjection of NSAIDs into the Ce uni- or bilaterally, produced antino-ciception with development of complete toler-ance over a 5-day period. Following the treat-ment period, morphine microinjection into the Ce failed to elicit antinociception, indicating cro- ss-tolerance to the antinociceptive effect of N SAIDs. In other words, the “non-opioid tolerant” rats showed cross-tolerance to morphine. Con-clusions: Our data confirmed the suggestion that NSAIDs interact with endogenous opioid systems, which likely play a key role in the development of tolerance to the antinociceptive effects of NSA IDs.展开更多
OBJECTIVE：Annona tomentosa R.E.Fr is a species not endemic to Brazil that belongs to the phytogeographic areas of the Amazon,Cerrado and Pantanal.Popularly known as“araticum rasteiro”or“araticum de moita”,A.tomen...OBJECTIVE：Annona tomentosa R.E.Fr is a species not endemic to Brazil that belongs to the phytogeographic areas of the Amazon,Cerrado and Pantanal.Popularly known as“araticum rasteiro”or“araticum de moita”,A.tomentosa is edible and tea made from the leaves has been used as an antiinflammatory by native communities.There is no scientific evidence for these uses of A.tomentosa,especially those related to the control of pain and inflammation.For this reason,in the present study we evaluated the antinociceptive and anti-inflammatory activities of partitions from the methanolic extract of A.tomentosa leaves（A.tomentosa leaf methanolic extract（ATFM）in hexane partition：ATFM-H;ATFM in dichloromethane partition：ATFM-D;ATFM in ethyl acetate partition：ATFM-Ac;ATFM in butanol partition：ATFM-B）in mice.METHODS：The antinociceptive effects of leaf extracts from A.tomentosa were evaluated by abdominal writhing and tail-flick tests,while the anti-inflammatory effects were evaluated by paw oedema and air-pouch tests.The locomotor activity was evaluated with the open-field test.Furthermore,we evaluated the possible action mechanism of A.tomentosa,using naloxone,nitro-L-arginine methyl ester,glibenclamide,atropine,naltrindole and norbinaltorphimine in tail-flick tests.The productions of tumor necrosis factorα（TNF-α）and interleukin（IL）-1βwere also evaluated.RESULTS：The chromatographic fractionation of the partitions of the methanolic extract from the leaves of A.tomentosa revealed the presence of diterpenes,flavonoids,and steroids compounds.From the analysis of the hexane partition kaurenoic acid was identified as the major component.ATFM-H and ATFM-D had a significant antinociceptive effect in acute pain models in mice.The ATFM-H showed central antinociceptive effect from the involvement of theδopioid receptors,without causing alterations in the locomotor activity of the mice,while ATFM-D was effective in decreasing paw oedema and TNF-α and IL-1β production.CONCLUSION：These results demonstrate that leaf extracts from A.tomentosa present antinociceptive and anti-inflammatory effects that can to be used in relieving algesic and inflammatory conditions.展开更多
In the central nervous system,the A6 noradrenaline(NA)and the B3 serotonin(5-HT)cell groups are well-recognized players in the descending antinociceptive system,while other NA/5-HT cell groups are not well characteriz...In the central nervous system,the A6 noradrenaline(NA)and the B3 serotonin(5-HT)cell groups are well-recognized players in the descending antinociceptive system,while other NA/5-HT cell groups are not well characterized.A5/A7 NA and B25-HT cells project to the spinal horn and form descending pathways.We recorded G-Ca MP6 green fluorescence signal intensities in the A5/A7 NA and the B25-HT cell groups of awake mice in response to acute tail pinch stimuli,acute heat stimuli,and in the context of a non-noxious control test,using fiber photometry with a calcium imaging system.We first introduced G-Ca MP6 in the A5/A7 NA or B25-HT neuronal soma,using transgenic mice carrying the tetracycline-controlled transactivator transgene under the control of either a dopamineβ-hydroxylase or a tryptophan hydroxylase-2 promoters and by the site-specific injection of adeno-associated virus(AAV-Tet O(3 G)-G-Ca MP6).After confirming the specific expression patterns of G-Ca MP6,we recorded G-Ca MP6 green fluorescence signals in these sites in awake mice in response to acute nociceptive stimuli.G-Ca MP6 fluorescence intensity in the A5,A7,and B2 cell groups was rapidly increased in response to acute nociceptive stimuli and soon after,it returned to baseline fluorescence intensity.This was not observed in the non-noxious control test.The results indicate that acute nociceptive stimuli rapidly increase the activities of A5/A7 NA or B25-HT neurons but the non-noxious stimuli do not.The present study suggests that A5/A7 NA or B25-HT neurons play important roles in nociceptive processing in the central nervous system.We suggest that A5/A7/B2 neurons may be new therapeutic targets.All performed procedures were approved by the Institutional Animal Use Committee of Kagoshima University(MD17105)on February 22,2018.展开更多
A number of studies have demonstrated that sex differentially affects responses to stress and pain. In this study, sex-related differences in pain responding were investigated in a gravity-induced analgesia model, whe...A number of studies have demonstrated that sex differentially affects responses to stress and pain. In this study, sex-related differences in pain responding were investigated in a gravity-induced analgesia model, where the effects of stressful high-gravity loading (1.5G or 2.0G for 10 min) on nociceptive behavior in male and female rats were investigated. In each rat, eight sites (nose, both forepaws, upper and lower back, both hind paws and tail) were selected to apply noxious stimuli using a von Frey-type needle stimulator. The threshold values of the withdrawal responses were measured. In order to confirm the involvement of endogenous opioids in gravity-induced antinociceptive effects, naloxone-HCl (an opioid antagonist) was used. Effective analgesic effects could be induced by strong (2.0G) gravity loading, and clear sex differences were observed. Gravity-induced analgesic effects were more effective in males than in females, indicating that males are more sensitive to stress than females judging from nociceptive modulation. Naloxone-HCl produced a more pronounced suppression of nociceptive behavior in male rats, suggesting that gravity loading may activate endogenous opioids more readily in males than in females.展开更多
Objective： To investigate the antinociceptive effects of Riluzole administered intraperitoneally in three hyperalgesia model of mice. Methods： Antinociceptive tests in C57BL mice were investigated with formalin test...Objective： To investigate the antinociceptive effects of Riluzole administered intraperitoneally in three hyperalgesia model of mice. Methods： Antinociceptive tests in C57BL mice were investigated with formalin test,acetic acid induced writhing test and tail-immersion test. The effects of intraperitoneally Riluzole 2 mg/kg ,4 mg/kg and 8 mg/kg on the pain threshold were observed. Result： We found that i.p. treatment with Riluzole （4 mg/kg and 8 mg/kg） blocked the second phase flinching behavior compared with vehicle （P 〈 0.05）, but not during the first phase in the formalin test. In addition to the formalin test, Riluzole at different dose （from 2 to 8 mg/kg） attenuated acetic acid induced writhing response when compared to vehicle group （P 〈 0.05）. In the tail-immersion test, Riluzole at the highest dose （8 mg/kg） caused significant increase in tail flick response latency as compared to vehicle animals or compared with Baseline （P 〈 0.05）. Conclusion： Our results suggest that glutamate release inhibitor Riluzole can attenuate nociceptive behavior and has differrent antinociceptive characteristic according to the various pain models.展开更多
Nociceptive pain is a cardinal feature of traumatic and inflammatory bone diseases.However,whether and how nociceptors actively regulate the immune response during bone regeneration remains unclear.Here,we found that ...Nociceptive pain is a cardinal feature of traumatic and inflammatory bone diseases.However,whether and how nociceptors actively regulate the immune response during bone regeneration remains unclear.Here,we found that neutrophil-triggered nociceptive ingrowth functioned as negative feedback regulation to inflammation during bone healing.A unique Il4ra^(+)Ccl2^(high) neutrophil subset drove intense postinjury TRPV1^(+)nociceptive ingrowth,which in return dissipated inflammation by activating the production of pro-resolving mediator lipoxin A4(LXA4)in osteoblasts.Mechanistically,osteoblastic autophagy activated by nociceptor-derived calcitonin gene-related peptide(CGRP)suppressed the nuclear translocation of arachidonate 5-lipoxygenase(5-LOX)to favor the LXA4 biosynthesis.Moreover,in alveolar bone from patients with Type Ⅱ diabetes,we found diminished nociceptive innervation correlated with reduced autophagy,increased inflammation,and impaired bone formation.Activating nociceptive nerves by spicy diet or topical administration of a clinical-approved TRPV1 agonist showed therapeutic benefits on alveolar bone healing in diabetic mice.These results reveal a critical neuroimmune interaction underlying the inflammation-regeneration balance during bone repairing and may lead to novel therapeutic strategies for inflammatory bone diseases.展开更多
Many cancers can exploit nearby neurons to promote their growth, but in extracranial tumors, these interactions are generally attributed to the secretion of growth factors or indirect effects(Padmanaban et al., 2024;R...Many cancers can exploit nearby neurons to promote their growth, but in extracranial tumors, these interactions are generally attributed to the secretion of growth factors or indirect effects(Padmanaban et al., 2024;Renz et al., 2018). Recently, in a study published in Nature, Wang's group(Zhi et al., 2025) discovered that gastric cancer(GC) can form neural circuits with adjacent nociceptive sensory nerves and utilize these malignant circuits to promote cancer growth and metastasis.展开更多
Background： Bispectral index （BIS） is considered very useful to guide anesthesia care in elderly patients, but its use is controversial for the evaluation of the adequacy of analgesia.This study compared the BIS ch...Background： Bispectral index （BIS） is considered very useful to guide anesthesia care in elderly patients, but its use is controversial for the evaluation of the adequacy of analgesia.This study compared the BIS changes in response to loss of consciousness （LOC） and loss of somatic response （LOS） to nociceptive stimuli between elderly and young patients receiving intravenous target-controlled infusion （TCI） of propofol and remifentanil.Methods： This study was performed on 52 elderly patients （aged 65-78 years） and 52 young patients （aged 25-58 years）, American Society of Anesthesiologists physical status Ⅰ or Ⅱ.Anesthesia was induced with propofol administered by TCI.A standardized noxious electrical stimulus （transcutaneous electrical nerve stimulation, [TENS]） was applied （50 Hz, 80 mA, 0.25 ms pulses for 4 s） to the ulnar nerve at increasing remifentanil predicted effective-site concentration （Ce） until patients lost somatic response to TENS.Changes in awake, prestimulus, poststimulus BIS, heart rate, mean arterial pressure, pulse oxygen saturation, predicted plasma concentration, Ce of propofol, and remifentanil at both LOC and LOS clinical points were investigated.Results： BISLOC in elderly group was higher than that in young patient group （65.4 ＆#177; 9.7 vs.57.6 ＆#177; 12.3） （t =21.58, P 〈 0.0001） after TCI propofol, and the propofol Ce at LOC was 1.6 ＆#177; 0.3 μg/ml in elderly patients, which was significantly lower than that in young patients （2.3 ＆#177; 0.5 μg/ml） （t =7.474, P 〈 0.0001）.As nociceptive stimulation induced BIS to increase, the mean of BIS maximum values after TENS was significantly higher than that before TENS in both age groups （t =8.902 and t =8.019, P 〈 0.0001）.With increasing Ce of remifentanil until patients lost somatic response to TENS, BISLOS was the same as the BISLOC in elderly patients （65.6 ＆#177; 10.7 vs.65.4 ＆#177; 9.7）, and there were no marked differences between elderly and young patient groups in BISawake, BISLOS, and Ce of remifentanil required for LOS.Conclusion： In elderly patients, BIS can be used as an indicator for hypnotic-analgesic balance and be helpful to guide the optimal administration of propofol and remifentanil individually.展开更多
Nociceptive-selective analgesia is often preferred over traditional methods,providing effective pain relief with minimum systemic side effects.The quaternary lidocaine derivative QX-314,is a promising local anesthetic...Nociceptive-selective analgesia is often preferred over traditional methods,providing effective pain relief with minimum systemic side effects.The quaternary lidocaine derivative QX-314,is a promising local anesthetic for achieving selective analgesia.However,due to its inability to penetrate the cell membrane,its efficacy is limited to intracellular administration.In this study,we aimed to develop an injectable electrospun fiber-hydrogel composite comprising QX-314-loaded poly(ε-caprolactone)electrospun fiber and capsaicin(Cap)-loaded F127 hydrogel(Fiber-QX314/Gel-Cap composite)for long-term and nociceptive-selective analgesia.The sequential and sustained release mechanism of Cap and QX-314 helped remarkably extend the sensory blockade duration up to 44.0 h,and prevent motor blockade.Specifically,our findings indicated that QX-314 can traverse the cell membrane through the transient receptor potential vanilloid 1 channel activated by Cap,thus targeting the intracellular Na+channel receptor to achieve selective analgesia.Moreover,the composite effectively allevi-ated incision pain by suppressing c-Fos expression in the dorsal root ganglion and reducing the activation of glial cells in the dorsal horn of the spinal cord.Consequently,the Fiber-QX314/Gel-Cap composite,designed for exceptional biosafety and sustained selective analgesia,holds great promise as a non-opioid analgesic.展开更多
Fibroblast growth factor(FGF)7,a member of FGF family,is initially found to be secreted from mesenchymal cells to repair epithelial tissues.However,its functions in the nervous system are largely unknown.The present s...Fibroblast growth factor(FGF)7,a member of FGF family,is initially found to be secreted from mesenchymal cells to repair epithelial tissues.However,its functions in the nervous system are largely unknown.The present study showed that FGF7 was a neuromodulator localized in the large dense-core vesicles(LDCVs)in nociceptive neurons.FGF7 was mainly expressed in small-diameter neurons of the dorsal root ganglion and could be transported to the dorsal spinal cord.Interestingly,FGF7 was mostly stored in LDCVs that did not contain neuropeptide substance P.Electrophysiological recordings in the spinal cord slice showed that buffer-applied FGF7 increased the amplitude of excitatory post-synaptic current evoked by stimulating the sensory afferent fibers.Behavior tests showed that intrathecally applied FGF7 potentiated the formalin-induced acute nociceptive response.Moreover,both acute and inflammatory nociceptive responses were significantly reduced in Fgf7-deficient mice.These results suggest that FGF7 exerts an excitatory modulation of nociceptive afferent transmission.展开更多
Objective： To assess the antinociceptive and anti-inflammatory properties of the aqueous extract of Armadillidium vulgare（AV）. Methods： The antinociceptive effect of AV（400, 600 and 800 mg/kg） was investigated i...Objective： To assess the antinociceptive and anti-inflammatory properties of the aqueous extract of Armadillidium vulgare（AV）. Methods： The antinociceptive effect of AV（400, 600 and 800 mg/kg） was investigated in mice using the acetic acid-induced writhing, formalin-induced nociceptive, and hot plate tests. Phlogogen-induced paw edema using carrageenan, dextran, or compound 48/80 as phlogogen was used as inflammatory models to evaluate AV＇s anti-inflammatory effect. Additionally, the bioactive substances glucosamine（GLc N） and taurine in AV were determined using high-performance liquid chromatography. Results： Oral treatment of the mice with AV（600 and 800 mg/kg） significantly reduced the number of writhes in the acetic acid-induced writhing test（P〈0.01） but not the hot plate test（P〉0.05）. All doses tested significantly inhibited paw-withdrawal during the second phase of the formalin-induced nociceptive model（P〈0.01）. AV demonstrated a strong anti-inflammatory effect in all those inflammatory models（P〈0.05）. Conclusions： AV has antinociceptive and anti-inflammatory effects, providing scientific evidence of the efficacy of its traditional use in pain treatment. Furthermore, GLc N and taurine contribute, at least in part, to the anti-inflammatory activity of AV.展开更多
Pain has been traditionally understood as a complex phenomenon involving various dimensions,including physical,sensory,cognitive,and emotional aspects,resulting in unpleasant sensations and affective responses.Individ...Pain has been traditionally understood as a complex phenomenon involving various dimensions,including physical,sensory,cognitive,and emotional aspects,resulting in unpleasant sensations and affective responses.Individual responses to pain can vary significantly,even when individuals are exposed to similar nociceptive stimuli or clinical conditions,with some individuals experiencing intense pain and others experiencing milder levels,suggesting the presence of pain resilience.Although recent advances in pain research have focused on susceptibility,the occurrence of pain,and related pathological mechanisms,there remains a dearth of comprehensive analysis of the neural mechanisms that underlie pain resilience,although peripheral mechanisms have begun to be revealed.展开更多
基金supported by grants from the National Natural Science Foundation of China (No.81071307,No.81271766)
文摘Despite its clinical importance, the underlying central mechanisms of pruritic behaviors are poorly understood. To investigate the role of nociceptive arcuate nucleus neurons in chloro-quine-induced pruritic behaviors in mice, we tested the effect of arcuate nucleus neurons and interscapular brown adipose tissue (IBAT) on itch produced by intradermal injection of chloroquine in the nape of the neck. Our results provide several lines of evidence for an important role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behavior: (1) Intradermal microinjection of chloro-quine resulted in a dramatic increase in itch behaviors accompanied by the activation of c-Fos positive neurons in arcuate nucleus; (2) Microinjection of chloroquine significantly increased IBAT temperature in the mice. These findings suggested that chloroquine-induced pruritic behaviors were associated with the activity of nociceptive arcuate nucleus neurons.
基金supported by the grants from the National Natural Science Foundation of China (31130066)the National Basic Research Development Program of China (2009CB522005 and 2011CBA00400)
文摘μ-opioid receptor （MOR） agonists such as morphine are powerful analgesics used for pain therapy. However, the use of these drugs is limited by their side-effects, which include antinociceptive tolerance and dependence. Earlier studies reported that MOR analgesic tolerance is reduced by blockade of 5-opioid receptors （DORs） that interact with MORs. Recent studies show that the MOR/DOR interaction in nociceptive afferent neurons in the dorsal root ganglion may contribute to morphine analgesic tolerance. Further analysis of the mechanisms for regulating the trafficking of receptors, ion channels and signaling molecules in nociceptive afferent neurons would help to understand the nociceptive mechanisms and improve pain therapy.
基金supported by the Fundamental Research Grant Scheme (FRGS No. 203/PPSP/6171162)
文摘Objective: This study was done to determine whether Tualang honey could prevent the altered nociceptive behaviour, with its associated changes of oxidative stress markers and morphology of the spinal cord,among the offspring of prenatally stressed rats.Methods: Pregnant rats were divided into three groups: control, stress, and stress treated with Tualang honey. The stress and stress treated with Tualang honey groups were subjected to restraint stress from day 11 of pregnancy until delivery. Ten week old male offspring(n = 9 from each group) were given formalin injection and their nociceptive behaviours were recorded. After 2 h, the rats were sacrificed, and their spinal cords were removed to assess oxidative stress activity and morphology. Nociceptive behaviour was analysed using repeated measures analysis of variance(ANOVA), while the levels of oxidative stress parameters and number of Nissl-stained neurons were analysed using a one-way ANOVA.Results: This study demonstrated that prenatal stress was associated with increased nociceptive behaviour, changes in the oxidative stress parameters and morphology of the spinal cord of offspring exposed to prenatal stress; administration of Tualang honey reduced the alteration of these parameters.Conclusion: This study provides a preliminary understanding of the beneficial effects of Tualang honey against the changes in oxidative stress and neuronal damage in the spinal cord of the offspring of prenatally stressed rats.
基金the Natural Science Foundation for Young Scientists of Shanxi Province,No.2006021040
文摘BACKGROUND： Previous morphological studies have demonstrated that group Ⅲ metabotropic glutamate receptors （mGluRs） are commonly found in nociceptive pathways, particularly in the terminals of primary afferent fibers in the spinal dorsal horn. OBJECTIVE： To investigate the role of group Ⅲ mGluRs in a rat model of spinal nociception by intrathecal administration of a selective agonist, L-Serine-O-phosphate （L-SOP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment. The study was performed at the Department of Physiology and Neurobiology, Shanxi Medical University, between March 2007 and May 2008. MATERIALS： L-SOP of group Ⅲ mGluRs （Tocris Cookson Ltd, UK）, formalin （Sigma, USA）, rabbit anti-c-Fos polyclonal antibody and biotin-labeled goat anti-rabbit IgG （Cell Signaling Technology, USA） were used in this study. METHODS： A total of 26 healthy Wistar rats, aged 1 month and weighing 100-120 g, were subjected to intrathecal catheter implantation. After 5-8 days, 10 rats were selected according to experimental requirements. L-SOP 250 nmol in 10 μL, or the equivalent volume of normal saline, was administered by intrathecal injection into the L3-5 region of the spinal cord in the experimental and control groups, respectively. After 15 minutes, formalin （5%, 50 μL） was subcutaneously injected into the plantar of the left hindpaw of each rat to establish formalin-induced pain models. MAIN OUTCOME MEASURES： Nociceptive behavioral responses and immunohistochemical examination of Fos expression. RESULTS： Intrathecal injection of L-SOP significantly attenuated the second phase nociceptive response compared with the control group （P 〈 0.05）, and Fos expression in the spinal dorsal horn was significantly decreased along with the number of Fos-like immunoreactive neurons （P 〈 0.05）. CONCLUSION： Group Ⅲ mGluRs are involved in the modulation of nociceptive signals, and their activation suppresses the transmission of nociceptive signals.
文摘Experiments were performed on 25 rats. Putative serotonergic antagonist, Cyproheptadine(Cyp), was applied microiontophoretically on the nucleus parafascicularis of the thalamus (Pf) andthe effect of Cyp on Pf nociceptive neuronal discharge was observed. The result suggested that Cypcan increase the spontaneous and evoked discharge rates of Pf nociceptive neuron, and that Cypmay antagonize the inhibitory effect of endogenous serotonin on the spontaneous and evokeddischarges of Pf nociceptive neurons.
文摘Background: Cardiac pain arising from acute coronary syndrome (ACS) is a multi-factorial phenomenon. Historically, episodes of cardiac pain have been captured using a one-dimensional numeric pain rating scale. Lacking in clinical practice are acute pain assessments that employ a comprehensive evaluation of an emergent ACS episode. Aim: To examine the sensory-discriminative, motivational-affective and cognitive-evaluative dimensions of ACS-related pain. Methods: A descriptive-correlational, repeated-measure design was used to collect data on 121 ACS patients of their cardiac pain intensity. The (numeric rating scale-NRS 0-10 scale) measured chest pain “Now” and “Worst pain in the previous 2 hours over 8 hours” and the McGill Pain Questionnaire Short-Form (MPQ-SF) measured pain at 4 hours. Results: Mean age was 67.6 ± 13, 50% were male, 60% had unstable angina and 40% had Non-ST-elevation myocardial infarction. Cardiac pain intensity scores remained in the mild range from 1.1 ± 2.2 to 2.4 ± 2.7. MPQ-SF: 66% described pain as distressing and 26% reported pain was horrible or excruciating. Participants described ACS pain quality as acute injury (nociceptive pain: heavy, cramping, stabbing), as nerve damage (neuropathic: gnawing, hot-burning, shooting) and as a mixture of acute and chronic pain qualities (aching, tender and throbbing). Conclusions: Patients reported both nociceptive and neuropathic cardiac pain. It is unclear if pain perceptions are due to: i) pathophysiology of clot formation, ii) occurrence of a first or repeated ACS episode, or iii) complex co-morbidities. Pain arising from ACS requires an understanding of the interplay of ischemic, metabolic and neuropathophysiological mechanisms that contribute to complex cardiac pain experiences.
文摘Bradykinin is an inflammatory mediator and one of the most potent endogenous pain-inducing substances. When released at the site of tissue damage or inflammation
基金supported by the National Natural Science Foundation of China(81974166,32271053,and 31872774).
文摘As a main structure of the limbic system,the hippocampus plays a critical role in pain perception and chronicity.The ventral hippocampal CA1(vCA1)is closely associated with negative emotions such as anxiety,stress,and fear,yet how vCA1 neurons encode nociceptive information remains unclear.Using in vivo electrophysiological recording,we characterized vCA1 pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli and were implicated in encoding stimuli modalities in naïve rats.Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions:the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli,whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties.Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors.Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats,whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain.These results provide direct evidence for the representations of nociceptive information in vCA1.
文摘Aim: Repeated microinjections of non-opioid an-algesics into the midbrain periaqueductal gray matter and rostral ventro-medial medulla induce antinociception with development of tolerance. Antinociception following systemic administra-tion of non-steroidal anti-inflammatory drugs (N SAIDs) also exhibit tolerance. Presently our aim was to investigate the development of tolerance to the antinociceptive effects of NSAIDs analgine, ketorolac, and xefocam microinjected into cen-tral nucleus of amygdala (Ce) in rats. Methods: Under anesthesia with thiopental a stainless steel guide cannula was stereotaxically implanted uni- laterally or bilaterally into the Ce using stereo-taxic atlas coordinates, and anchored to the cra- nium by dental cement. Five days after surgery, 3 μl of these NSAIDs were injected via the injec-tion cannula while the rat was gently restrained. Twenty min post microinjection, i.e. 10-min be-fore the peak of the drugs’ effect is normally rea- ched, animals were tested with tail flick (TF) and hot plate (HP) tests. On the 5th experimental day all animals received a Ce microinjection of mor-phine. Results: Daily microinjection of NSAIDs into the Ce uni- or bilaterally, produced antino-ciception with development of complete toler-ance over a 5-day period. Following the treat-ment period, morphine microinjection into the Ce failed to elicit antinociception, indicating cro- ss-tolerance to the antinociceptive effect of N SAIDs. In other words, the “non-opioid tolerant” rats showed cross-tolerance to morphine. Con-clusions: Our data confirmed the suggestion that NSAIDs interact with endogenous opioid systems, which likely play a key role in the development of tolerance to the antinociceptive effects of NSA IDs.
文摘OBJECTIVE：Annona tomentosa R.E.Fr is a species not endemic to Brazil that belongs to the phytogeographic areas of the Amazon,Cerrado and Pantanal.Popularly known as“araticum rasteiro”or“araticum de moita”,A.tomentosa is edible and tea made from the leaves has been used as an antiinflammatory by native communities.There is no scientific evidence for these uses of A.tomentosa,especially those related to the control of pain and inflammation.For this reason,in the present study we evaluated the antinociceptive and anti-inflammatory activities of partitions from the methanolic extract of A.tomentosa leaves（A.tomentosa leaf methanolic extract（ATFM）in hexane partition：ATFM-H;ATFM in dichloromethane partition：ATFM-D;ATFM in ethyl acetate partition：ATFM-Ac;ATFM in butanol partition：ATFM-B）in mice.METHODS：The antinociceptive effects of leaf extracts from A.tomentosa were evaluated by abdominal writhing and tail-flick tests,while the anti-inflammatory effects were evaluated by paw oedema and air-pouch tests.The locomotor activity was evaluated with the open-field test.Furthermore,we evaluated the possible action mechanism of A.tomentosa,using naloxone,nitro-L-arginine methyl ester,glibenclamide,atropine,naltrindole and norbinaltorphimine in tail-flick tests.The productions of tumor necrosis factorα（TNF-α）and interleukin（IL）-1βwere also evaluated.RESULTS：The chromatographic fractionation of the partitions of the methanolic extract from the leaves of A.tomentosa revealed the presence of diterpenes,flavonoids,and steroids compounds.From the analysis of the hexane partition kaurenoic acid was identified as the major component.ATFM-H and ATFM-D had a significant antinociceptive effect in acute pain models in mice.The ATFM-H showed central antinociceptive effect from the involvement of theδopioid receptors,without causing alterations in the locomotor activity of the mice,while ATFM-D was effective in decreasing paw oedema and TNF-α and IL-1β production.CONCLUSION：These results demonstrate that leaf extracts from A.tomentosa present antinociceptive and anti-inflammatory effects that can to be used in relieving algesic and inflammatory conditions.
基金supported by JSPS KAKENHI grants(Nos.19K17093 to SM20K06858 to AYamashita16H05130 to TK)and CREST JST(No.JPMJCR1656 to AYamanaka)。
文摘In the central nervous system,the A6 noradrenaline(NA)and the B3 serotonin(5-HT)cell groups are well-recognized players in the descending antinociceptive system,while other NA/5-HT cell groups are not well characterized.A5/A7 NA and B25-HT cells project to the spinal horn and form descending pathways.We recorded G-Ca MP6 green fluorescence signal intensities in the A5/A7 NA and the B25-HT cell groups of awake mice in response to acute tail pinch stimuli,acute heat stimuli,and in the context of a non-noxious control test,using fiber photometry with a calcium imaging system.We first introduced G-Ca MP6 in the A5/A7 NA or B25-HT neuronal soma,using transgenic mice carrying the tetracycline-controlled transactivator transgene under the control of either a dopamineβ-hydroxylase or a tryptophan hydroxylase-2 promoters and by the site-specific injection of adeno-associated virus(AAV-Tet O(3 G)-G-Ca MP6).After confirming the specific expression patterns of G-Ca MP6,we recorded G-Ca MP6 green fluorescence signals in these sites in awake mice in response to acute nociceptive stimuli.G-Ca MP6 fluorescence intensity in the A5,A7,and B2 cell groups was rapidly increased in response to acute nociceptive stimuli and soon after,it returned to baseline fluorescence intensity.This was not observed in the non-noxious control test.The results indicate that acute nociceptive stimuli rapidly increase the activities of A5/A7 NA or B25-HT neurons but the non-noxious stimuli do not.The present study suggests that A5/A7 NA or B25-HT neurons play important roles in nociceptive processing in the central nervous system.We suggest that A5/A7/B2 neurons may be new therapeutic targets.All performed procedures were approved by the Institutional Animal Use Committee of Kagoshima University(MD17105)on February 22,2018.
文摘A number of studies have demonstrated that sex differentially affects responses to stress and pain. In this study, sex-related differences in pain responding were investigated in a gravity-induced analgesia model, where the effects of stressful high-gravity loading (1.5G or 2.0G for 10 min) on nociceptive behavior in male and female rats were investigated. In each rat, eight sites (nose, both forepaws, upper and lower back, both hind paws and tail) were selected to apply noxious stimuli using a von Frey-type needle stimulator. The threshold values of the withdrawal responses were measured. In order to confirm the involvement of endogenous opioids in gravity-induced antinociceptive effects, naloxone-HCl (an opioid antagonist) was used. Effective analgesic effects could be induced by strong (2.0G) gravity loading, and clear sex differences were observed. Gravity-induced analgesic effects were more effective in males than in females, indicating that males are more sensitive to stress than females judging from nociceptive modulation. Naloxone-HCl produced a more pronounced suppression of nociceptive behavior in male rats, suggesting that gravity loading may activate endogenous opioids more readily in males than in females.
基金Key Laboratory Foundation of Jiangsu Province Department of Health(WK200501)
文摘Objective： To investigate the antinociceptive effects of Riluzole administered intraperitoneally in three hyperalgesia model of mice. Methods： Antinociceptive tests in C57BL mice were investigated with formalin test,acetic acid induced writhing test and tail-immersion test. The effects of intraperitoneally Riluzole 2 mg/kg ,4 mg/kg and 8 mg/kg on the pain threshold were observed. Result： We found that i.p. treatment with Riluzole （4 mg/kg and 8 mg/kg） blocked the second phase flinching behavior compared with vehicle （P 〈 0.05）, but not during the first phase in the formalin test. In addition to the formalin test, Riluzole at different dose （from 2 to 8 mg/kg） attenuated acetic acid induced writhing response when compared to vehicle group （P 〈 0.05）. In the tail-immersion test, Riluzole at the highest dose （8 mg/kg） caused significant increase in tail flick response latency as compared to vehicle animals or compared with Baseline （P 〈 0.05）. Conclusion： Our results suggest that glutamate release inhibitor Riluzole can attenuate nociceptive behavior and has differrent antinociceptive characteristic according to the various pain models.
基金The National Natural Science Foundation of China(No.82130027,82301020,82100966)Young Elite Scientists Sponsorship Program by CAST(2024QNRC001)+5 种基金The China Postdoctoral Science Foundation(2023M732283)The National Key Research and Development Program of China(No.2023YFC2413600)The Shanghai Sailing Program(23YF1422000,21YF1424400)Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZLCX20212400)Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)Shanghai Pujiang Program(24PJD054).
文摘Nociceptive pain is a cardinal feature of traumatic and inflammatory bone diseases.However,whether and how nociceptors actively regulate the immune response during bone regeneration remains unclear.Here,we found that neutrophil-triggered nociceptive ingrowth functioned as negative feedback regulation to inflammation during bone healing.A unique Il4ra^(+)Ccl2^(high) neutrophil subset drove intense postinjury TRPV1^(+)nociceptive ingrowth,which in return dissipated inflammation by activating the production of pro-resolving mediator lipoxin A4(LXA4)in osteoblasts.Mechanistically,osteoblastic autophagy activated by nociceptor-derived calcitonin gene-related peptide(CGRP)suppressed the nuclear translocation of arachidonate 5-lipoxygenase(5-LOX)to favor the LXA4 biosynthesis.Moreover,in alveolar bone from patients with Type Ⅱ diabetes,we found diminished nociceptive innervation correlated with reduced autophagy,increased inflammation,and impaired bone formation.Activating nociceptive nerves by spicy diet or topical administration of a clinical-approved TRPV1 agonist showed therapeutic benefits on alveolar bone healing in diabetic mice.These results reveal a critical neuroimmune interaction underlying the inflammation-regeneration balance during bone repairing and may lead to novel therapeutic strategies for inflammatory bone diseases.
基金supported by the Major Project of Natural Science Foundation of Zhejiang Province (D25H300005)the National Natural Science Foundation of China (32000799)。
文摘Many cancers can exploit nearby neurons to promote their growth, but in extracranial tumors, these interactions are generally attributed to the secretion of growth factors or indirect effects(Padmanaban et al., 2024;Renz et al., 2018). Recently, in a study published in Nature, Wang's group(Zhi et al., 2025) discovered that gastric cancer(GC) can form neural circuits with adjacent nociceptive sensory nerves and utilize these malignant circuits to promote cancer growth and metastasis.
文摘Background： Bispectral index （BIS） is considered very useful to guide anesthesia care in elderly patients, but its use is controversial for the evaluation of the adequacy of analgesia.This study compared the BIS changes in response to loss of consciousness （LOC） and loss of somatic response （LOS） to nociceptive stimuli between elderly and young patients receiving intravenous target-controlled infusion （TCI） of propofol and remifentanil.Methods： This study was performed on 52 elderly patients （aged 65-78 years） and 52 young patients （aged 25-58 years）, American Society of Anesthesiologists physical status Ⅰ or Ⅱ.Anesthesia was induced with propofol administered by TCI.A standardized noxious electrical stimulus （transcutaneous electrical nerve stimulation, [TENS]） was applied （50 Hz, 80 mA, 0.25 ms pulses for 4 s） to the ulnar nerve at increasing remifentanil predicted effective-site concentration （Ce） until patients lost somatic response to TENS.Changes in awake, prestimulus, poststimulus BIS, heart rate, mean arterial pressure, pulse oxygen saturation, predicted plasma concentration, Ce of propofol, and remifentanil at both LOC and LOS clinical points were investigated.Results： BISLOC in elderly group was higher than that in young patient group （65.4 ＆#177; 9.7 vs.57.6 ＆#177; 12.3） （t =21.58, P 〈 0.0001） after TCI propofol, and the propofol Ce at LOC was 1.6 ＆#177; 0.3 μg/ml in elderly patients, which was significantly lower than that in young patients （2.3 ＆#177; 0.5 μg/ml） （t =7.474, P 〈 0.0001）.As nociceptive stimulation induced BIS to increase, the mean of BIS maximum values after TENS was significantly higher than that before TENS in both age groups （t =8.902 and t =8.019, P 〈 0.0001）.With increasing Ce of remifentanil until patients lost somatic response to TENS, BISLOS was the same as the BISLOC in elderly patients （65.6 ＆#177; 10.7 vs.65.4 ＆#177; 9.7）, and there were no marked differences between elderly and young patient groups in BISawake, BISLOS, and Ce of remifentanil required for LOS.Conclusion： In elderly patients, BIS can be used as an indicator for hypnotic-analgesic balance and be helpful to guide the optimal administration of propofol and remifentanil individually.
基金supported by the Joint Funds of National Natural Science Foundation of China(U22A20276)the“Five and five”Project of the Third Affiliated Hospital of Sun Yat-Sen University(2023WW501)+9 种基金the Guangdong Provincial Science and Technology Program(202201020429)the Science and Technology Planning Project of Guangdong Province-Regional Innovation Capacity and Support System Construction(2023B110006)the National Key Research and Development Program of China(2019YFA0111300)the National Natural Science Foundation of China(52373166,22277155,32001012)the Science and Technology Program of Guangzhou(2024A04J6572,202102010217,202102010190)the Guangdong Provincial Pearl River Talents Program(2019QN01Y131)the Science and Technology Planning Project of Guangdong Province of China(2020A0505100035)the Guangdong Basic and Applied Basic Research Foundation(2019A1515011852,2021A1515012318)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20233217)the Natural Science Foundation of Guangdong Province for Distinguished Young Scholar(2024B1515020025),and the China Primary Health Care Foundation(2022-003).
文摘Nociceptive-selective analgesia is often preferred over traditional methods,providing effective pain relief with minimum systemic side effects.The quaternary lidocaine derivative QX-314,is a promising local anesthetic for achieving selective analgesia.However,due to its inability to penetrate the cell membrane,its efficacy is limited to intracellular administration.In this study,we aimed to develop an injectable electrospun fiber-hydrogel composite comprising QX-314-loaded poly(ε-caprolactone)electrospun fiber and capsaicin(Cap)-loaded F127 hydrogel(Fiber-QX314/Gel-Cap composite)for long-term and nociceptive-selective analgesia.The sequential and sustained release mechanism of Cap and QX-314 helped remarkably extend the sensory blockade duration up to 44.0 h,and prevent motor blockade.Specifically,our findings indicated that QX-314 can traverse the cell membrane through the transient receptor potential vanilloid 1 channel activated by Cap,thus targeting the intracellular Na+channel receptor to achieve selective analgesia.Moreover,the composite effectively allevi-ated incision pain by suppressing c-Fos expression in the dorsal root ganglion and reducing the activation of glial cells in the dorsal horn of the spinal cord.Consequently,the Fiber-QX314/Gel-Cap composite,designed for exceptional biosafety and sustained selective analgesia,holds great promise as a non-opioid analgesic.
基金This work was supported by the National Natural Science Foundation of China(31130066)the Strategic Priority Research Program(B)of Chinese Academy of Sciences(XDB01020300).
文摘Fibroblast growth factor(FGF)7,a member of FGF family,is initially found to be secreted from mesenchymal cells to repair epithelial tissues.However,its functions in the nervous system are largely unknown.The present study showed that FGF7 was a neuromodulator localized in the large dense-core vesicles(LDCVs)in nociceptive neurons.FGF7 was mainly expressed in small-diameter neurons of the dorsal root ganglion and could be transported to the dorsal spinal cord.Interestingly,FGF7 was mostly stored in LDCVs that did not contain neuropeptide substance P.Electrophysiological recordings in the spinal cord slice showed that buffer-applied FGF7 increased the amplitude of excitatory post-synaptic current evoked by stimulating the sensory afferent fibers.Behavior tests showed that intrathecally applied FGF7 potentiated the formalin-induced acute nociceptive response.Moreover,both acute and inflammatory nociceptive responses were significantly reduced in Fgf7-deficient mice.These results suggest that FGF7 exerts an excitatory modulation of nociceptive afferent transmission.
文摘Objective： To assess the antinociceptive and anti-inflammatory properties of the aqueous extract of Armadillidium vulgare（AV）. Methods： The antinociceptive effect of AV（400, 600 and 800 mg/kg） was investigated in mice using the acetic acid-induced writhing, formalin-induced nociceptive, and hot plate tests. Phlogogen-induced paw edema using carrageenan, dextran, or compound 48/80 as phlogogen was used as inflammatory models to evaluate AV＇s anti-inflammatory effect. Additionally, the bioactive substances glucosamine（GLc N） and taurine in AV were determined using high-performance liquid chromatography. Results： Oral treatment of the mice with AV（600 and 800 mg/kg） significantly reduced the number of writhes in the acetic acid-induced writhing test（P〈0.01） but not the hot plate test（P〉0.05）. All doses tested significantly inhibited paw-withdrawal during the second phase of the formalin-induced nociceptive model（P〈0.01）. AV demonstrated a strong anti-inflammatory effect in all those inflammatory models（P〈0.05）. Conclusions： AV has antinociceptive and anti-inflammatory effects, providing scientific evidence of the efficacy of its traditional use in pain treatment. Furthermore, GLc N and taurine contribute, at least in part, to the anti-inflammatory activity of AV.
基金supported by grants from the National Natural Science Foundation of China(82304459).
文摘Pain has been traditionally understood as a complex phenomenon involving various dimensions,including physical,sensory,cognitive,and emotional aspects,resulting in unpleasant sensations and affective responses.Individual responses to pain can vary significantly,even when individuals are exposed to similar nociceptive stimuli or clinical conditions,with some individuals experiencing intense pain and others experiencing milder levels,suggesting the presence of pain resilience.Although recent advances in pain research have focused on susceptibility,the occurrence of pain,and related pathological mechanisms,there remains a dearth of comprehensive analysis of the neural mechanisms that underlie pain resilience,although peripheral mechanisms have begun to be revealed.
