Substance P Content Research Articles

Modulating Ocular Surface Pain Through Neurokinin-1 Receptor Blockade.

PurposeThe purpose of this study was to test the role of substance P (SP) and its receptor neurokinin 1 (NK1R) on ocular surface pain.MethodsEight-week-old C57BL6/N (wild type [WT]) and B6.Cg-Tac1tm1Bbm/J (TAC1-KO) male mice were used. 5 M NaCl was topically applied on the cornea, followed by topical fosaprepitant 2, 10, and 50 mg/mL; 4 mg/mL oxybuprocaine chloride, or 0.1% diclofenac. Th eye wiping test was used to quantify ocular surface pain. SP content was quantified in the tear fluid and trigeminal ganglia (TG), and TAC1 mRNA was assessed in the cornea. Corneas were immunostained for β3-tubulin and NK1R, or CD45, to quantify leukocyte infiltration.ResultsTAC1-KO mice displayed a significant reduction of ocular pain (P < 0.001). Similarly, a single dose of 10 or 50 mg/mL fosaprepitant applied topically to WT mice reduced ocular pain as compared to vehicle (P < 0.001). Fosaprepitant 2 mg/mL, instead, induced corneal analgesia only when it was administered for 10 days, 6 times/day (P < 0.05). Diclofenac or oxybuprocaine reduced corneal nociception when compared to vehicle or fosaprepitant (P < 0.05). Fosaprepitant or oxybuprocaine groups showed lower SP content in tear secretions and TG (P < 0.05), and reduction in TAC1 mRNA (P < 0.05), and leukocyte infiltration (P < 0.05) in the cornea. Colocalization of NK1R and β3-tubulin was detected in mouse corneas.ConclusionsTopical administration of the NK1R antagonist fosaprepitant effectively reduces ocular surface nociception by decreasing SP release in the tear fluid and TG, and corneal leukocyte infiltration. Fosaprepitant repurposing shows promise for the treatment of ocular pain.

Oropharyngeal Dysphagia in Older People is Associated with Reduced Pharyngeal Sensitivity and Low Substance P and CGRP Concentration in Saliva.

Substance P (SP) and Calcitonine gene-related peptide (CGRP) are released by sensory nerve fibers in the oropharynx. Patients with oropharyngeal dysphagia (OD) present reduced oropharyngeal sensitivity and low SP concentration in saliva. We aimed to assess the concentration of salivary SP and CGRP in healthy volunteers, and older people without and with OD, and the relationship with pharyngeal sensory threshold. We included 15 healthy volunteers, 14 healthy elderly and 14 elderly with OD. Swallow function was assessed by videofluoroscopy (VFS). Pharyngeal sensory threshold was assessed by intrapharyngeal electrical stimulation. Hydration and phase angle were assessed by bioimpedance. Saliva samples were collected with a Salivette® to determine SP and CGRP concentration by ELISA. Elderly patients with OD presented impaired safety of swallow (PAS 4.38 ± 0.77 p < 0.0001 vs. healthy volunteers = 1 and healthy elderly = 1.43 ± 0.51). Healthy elderly and elderly with OD presented a reduction in intracellular water and saliva volume (healthy elderly, 592.86 ± 327.79μl, p = 0.0004; elderly with OD, 422.00 ± 343.01μl, p = 0.0001 vs healthy volunteers, 1333.33 ± 615.91μl, r = 0.6621, p < 0.0001). Elderly patients with OD presented an impairment in pharyngeal sensory threshold (10.80 ± 3.92mA vs. healthy volunteers, 5.74 ± 2.57mA; p = 0.007) and a reduction in salivary SP (129.34pg/ml vs. healthy volunteers: 173.89pg/ml; p = 0.2346) and CGRP levels (24.17pg/ml vs. healthy volunteers: 508.18pg/ml; p = 0.0058). There was a negative correlation between both SP and CGRP concentrations and pharyngeal sensory threshold (r = - 0.450, p = 0.024; r = - 0.4597, p = 0.036, respectively), but only SP identified elderly patients with OD with higher pharyngeal sensory threshold. Elderly patients with OD presented hydropenia and sarcopenia, reduced salivary SP and CGRP and impaired pharyngeal sensitivity. Our study suggests SP levels in saliva as a potential biomarker to monitor pharyngeal sensitivity in elderly patients with OD.

Effect of intranasal acupuncture on neurogenic inflammation in allergic rhinitis rabbits

To observe the effect of intranasal acupuncture on allergic rhinitis (AR), and expression of substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) proteins in the nasal mucosa and contents of serum immunoglobulin E (IgE), interleukin 4 (IL-4) and interferon-γ (IFN-γ) in AR rabbits, so as to explore its mechanisms underlying improvement of AR. New Zealand rabbits were randomly divided into normal control, AR model, non-acupuoint acupuncture (NAA) and intranasal acupuncture (INA) groups, with 8 rabbits in each group. The AR model was established by intra-peritoneal injection of egg protein and nasal mucosal stimulation. In the INA group, bilateral "Neiyingxiang" (EX-HN9) within the nasal cavity (the anterior attachment area of the inferior turbinate, about 1 cm away from the nasal limen) were acupunctured by mani-pulating the filiform needles for a while with uniform reinforcing and reducing methods, followed by keeping the needles for 20 min. In the NAA group, shallow acupuncture was applied to the skin of the outer margin of the cheeks, followed by keeping the needle for 20 min. The acupuncture treatment was conducted once every other day for 7 days. The symptoms of sneezing frequency, nasal secretion amount and nasal itching were scored. The expression levels of SP, VIP and NPY in the nasal mucosa tissue were detected by immunohistochemistry, and the serum IgE, IL-4, and IFN-γ contents were detected by ELISA. After modelling, the symptom score, expression of SP and VIP, and serum IgE and IL-4 contents were significantly higher (P<0.01,P<0.05), NPY expression and serum IFN-γ content significantly lower (P<0.05, P<0.01) in the model group than in the normal control group. Following the intervention, the symptom scores, expressions of SP and VIP, and serum IgE and IL-4 contents were remarkably decreased (P<0.05, P<0.01), while the NPY expression and serum IFN-γ content were significantly up-regulated (P<0.05, P<0.01) in the INA group than in the model group. The effects of INA group were significantly superior to those of NAA group in reducing symptom score, SP and VIP expression, and serum IgE and IL-4 contents and up-regulating NPY expression and IFN-γcontent (P<0.05, P<0.01). There were a positive correlation between the expressions of SP and VIP and contents of serum IgE and IL-4 (P<0.05), and a negative correlation between the expressions of SP and VIP and IFN-γ content (P<0.05). INA treatment can relieve symptoms of AR in AR rabbits, which may be associated with its effects in regulating the expression of SP, VIP and NPY of the nasal mucosa, and contents of serum IgE, IL-4 and IFN-γ to improve neurogenic inflammation.

Mechanisms underlying the promotion of 5-hydroxytryptamine secretion in enterochromaffin cells of constipation mice by Bifidobacterium and Lactobacillus.

5-Hydroxytryptamine (5-HT) could play a role in alleviating symptoms in constipation. However, the mechanism underlying the role of intestinal flora in the promotion of 5-HT secretion by enterochromaffin cells (ECs) and regulation of the gastrointestinal endocrine system remains unclear. A constipation mouse model was constructed, and the 5-HT, chromogranin A (CGA), substance P (SP), motilin (MTL), dopamine, and noradrenaline expression levels were measured using enzyme-linked immunosorbent assay(Elisa) and immunofluorescence, and key proteins, such as the transient receptor potential (TRP) ion channels/tryptophan hydroxylase (TPH) and olfactory receptor (OR), were determined using western blot. Flow cytometry and in vivo imaging were used to observe microbial colonization in the intestinal tracts of mice. Bifidobacterium animalis F1-7 (F1-7), Lactobacillus paraccasei F34-3 (F34-3), and Lactobacillus plantarum FWDG (FWDG) promoted 5-HT secretion. F1-7 and F34-3 induced CGA expression, increased catecholamine secretion, and activated the CGA/α2A adrenoreceptor (ADRα2A) cascade signal in ECs. FWDG increased noradrenaline levels and activated the ADRα2A signal in ECs. SP content increased in F1-7 and F34-3, and MTL expression increased in FWDG via the above signal. F1-7 and F34-3 downregulated TRPV4 and upregulated TPH, whereas FWDG upregulated OR2A4 for promoting 5-HT secretion by ECs. Finally, we observed that F1-7, F34-3, and FWDG were well colonized in the large intestine. F1-7, F34-3, and FWDG promoted 5-HT secretion in ECs of constipation mice by activating the CGA/ADRα2A cascade signal and regulating the TRP/TPH-OR pathways.

Perioperative transcutaneous electrical acupoint stimulation for improving postoperative gastrointestinal function: A randomized controlled trial

BackgroundPostoperative gastrointestinal dysfunction (PGD) is one of the most common complications in patients undergoing major abdominal surgery. Acupuncture has been used widely in gastrointestinal diseases due to its effectiveness and minimally invasive nature. ObjectiveThis study evaluated the efficacy of using transcutaneous electrical acupoint stimulation (TEAS) during the surgery and postoperative recovery in patients with gastric and colorectal surgery for improving postoperative gastrointestinal function. Design, setting, participants and interventionsA total of 280 patients undergoing abdominal surgery were stratified by type of surgery (i.e., gastric or colorectal surgery) and randomly allocated into the TEAS group (group T) or the sham group (group S). Patients in group T received TEAS at LI4, PC6, ST36 and ST37. Patients in group S received pseudo-TEAS at sham acupoints. The stimulation was given from 30 min before anesthesia until the end of surgery. The same treatment was performed at 9 am on the 1st, 2nd and 3rd days after surgery, until the recovery of flatus in patients. Main outcome measuresThe primary outcome was the time to the first bowel motion, as detected by auscultation. The secondary outcomes included the first flatus and ambulation time, changes of perioperative substance P (SP), incidence of PGD, postoperative pain, postoperative nausea and vomiting (PONV) and some economic indicators. ResultsThe time to first bowel motion, first flatus and first ambulation in group T was much shorter than that in group S (P < 0.01). In patients undergoing colorectal surgery, the concentration of SP was lower in group T than in group S on the third day after the operation (P < 0.05). The average incidence of PGD in all patients was 25%, and the frequency of PGD was significantly lower in group T than in group S (18.6% vs. 31.4%, respectively; P < 0.05). TEAS treatment (odds ratio = 0.498; 95% confidence interval: 0.232–0.786) and type of surgery were relevant factors for the development of PGD. Postoperative pain score and PONV occurrence were significantly lower in group T (P < 0.01). Postoperative hospitalization days and the resulting cost to patients were greatly reduced in the TEAS group (P < 0.01). ConclusionPerioperative TEAS was able to promote the recovery of postoperative gastrointestinal function, reduce the incidence of PGD and PONV. The concentration of SP was decreased by TEAS treatment, which indicates that the brain-gut axis may play a role in how TEAS regulates gastrointestinal function. Trial registrationChinese Clinical Trial Registry, ChiCTR1900023263.

Adoption of computerized tomography images in detection of lung nodules and analysis of neuropeptide correlative substances under deep learning algorithm

To solve the problems of low sensitivity and high false positive rate of current lung nodule detection technology, and to explore the correlation between neuropeptide correlative substances and lung nodules, in the study, the deep learning-based computerized tomography (CT) images were used to detect lung nodules. Specifically, a multi-scale three-dimensional convolutional neural network (CNN) was established for lung nodule detection. First, high-quality candidate nodules were obtained by a two-dimensional CNN. Then, three-dimensional CNNs of different scales were constructed for candidate nodules of different sizes, and the fused model was used to classify candidate nodules. Finally, the detection results of the single network, the two-dimensional CNN, and the fused network were compared. Meanwhile, the serum levels of vasoactive intestinal peptide (VIP) and substance P (SP) were detected in patients with lung injury caused by lung nodules, so as to analyze the correlation between neuropeptide correlative substances and lung nodules. The results showed that the detection sensitivity of the fused network was 85.8% and 92.9% when the number of false positives was 1 and 4, respectively, which were higher than that of the single network and two-dimensional CNN. However, the content of VIP in the serum of patients with pulmonary nodules was significantly reduced, while the content of SP was significantly increased. Therefore, the algorithm proposed in this study can effectively improve the sensitivity of the pulmonary nodule detection system and reduce false positive rate; at the same time, neuropeptide correlative substances may be correlated with the lung injury caused by pulmonary nodules.

The effects of two different intensities of aerobic training protocols on pain and serum neuro-biomarkers in women migraineurs: a randomized controlled trail.

We have a weak understanding of how aerobic training may influence migraine, and the optimal parameters for exercise regimens as migraine therapy are not clear. The objectives of this study were to assess, first, effects of two different intensities of aerobic exercise on migraine headache indices; second, serum neuro-biomarker in women migraineurs. A total of 45 non-athlete female migraine patients were selected by a neurologist and randomly divided into three groups: control (CON), moderate-intensity aerobic training (MOD T), and high-intensity aerobic training (HIGH T). Before and after the training protocol, body composition factors, migraine pain indices, VO2max, and serum Adenylate-Cyclase Activating Polypeptide (PACAP) and Substance P (SP) were measured. Exercise training protocol includes two different intensities of aerobic exercise: Moderate (13-15 Borg Scale, 60-80% HRmax) and High (15-17 Borg Scale, 65-95% HRmax). Moderate-intensity aerobic training (MOD T) reduced headache intensity, frequency, and duration in women with migraine (p < 0.001, for all). Also, high-intensity aerobic training (HIGH T) reduced headache intensity, frequency, and duration (p < 0.001, for all). However, for headache intensity and duration, MOD T was effective rather than HIGH T (p < 0.001; p ≤ 0.05, respectively). In addition, neither MOD T nor HIGH T could not alter PACAP and SP contents (p = 0.712; p = 0.249, respectively). Our results demonstrated that either MOD T or HIGH T could modify migraine pain indices but neither MOD T nor HIGH T could not alter the PACAP and SP contents in women with migraine.

Effects of electroacupuncture on pain behavior and pain-related factors in spinal cord dorsal horn and dorsal root ganglia of rats with knee osteoarthritis

To observe the effect of electroacupuncture(EA) on the pain behavior and prostaglandin E2 (PGE2), calcitonin gene-related peptide (CGRP) and substance P (SP) in the spinal cord dorsal horn and dorsal root ganglia (DRG) of rats with knee osteoarthritis (KOA), so as to explore the mechanisms of EA underlying improvement of chronic pain in KOA rats. Thirty-two female SD rats were randomly divided into blank group, control group, model group and EA group, with 8 rats in each group. Rats in the control group were injected with 50 μL of 0.9% sodium chloride solution into the left knee joint cavity, and rats in the model and EA groups were injected with 50 μL of Monosodium iodoacetate in the left knee joint. EA(2 Hz/100 Hz, ＜2 mA) was applied to left "Yanglingquan"(GB34) and "Neixiyan" (EX-LE4) for 15 min, once daily, 5 days a course with a total of 2 courses. Paw withdrawal latency (PWL) and mechanical pain threshold (PWT) were tested by Plantar Test and Von Frey, separately. After the last pain test, the contents of PGE2, CGRP and SP in the left lumbar (L) 3-L5 DRG and L3-L5 spinal dorsal horn were detected by ELISA. Compared with the blank group, the PWL and PWT of the rats in the model group were significantly decreased (P<0.01), and the contents of PGE2, CGRP and SP in the DRG and spinal dorsal horn were significantly increased (P<0.01, P<0.05). There were no statistically significant differences in PWL, PWT, contents of PGE2, CGRP and SP in DRG and spinal dorsal horn between the blank group and the control group (P>0.05). Compared with the model group, the PWL and PWT of rats in the EA group were significantly increased (P<0.01), and the contents of PGE2, CGRP and SP in the DRG and spinal dorsal horn were significantly decreased (P<0.01, P<0.05). EA of GB34 and EX-LE4 can reduce the levels of pain-related factors PGE2, CGRP and SP in the DRG and spinal dorsal horn, thereby relieving spinal hyperalgesia in rats with KOA.

Role of Substance P in the Pathophysiology of Inflammatory Bowel Disease and Its Correlation With the Degree of Inflammation.

Inflammatory bowel disease (IBD) is a multi-factorial, chronic inflammation of the gastrointestinal tract, containing ulcerative colitis (UC) and Crohn's disease (CD). In UC, inflammation and sores are confined morphologically and microscopically to the mucosa, the innermost surface of the colon and the rectum. Although, in CD, the infection is granulomatous and transmural, affecting the entire gastrointestinal tract from the mouth to the anus, with the skip area in-between. A Neuropeptide, substance P (SP), which acts as a neurotransmitter and as a neuromodulator, plays a vital role in the brain-gut axis under stress. Owing to the pro-inflammatory effects of SP, neuropeptide dysregulation induces inflammation in the intestine. There are variations in the distribution of substance P immunoreactive fibres in the various intestinal layers. The highest concentration of SP is in the mucosa and the lowest concentration in the lamina propria of the intestinal muscular membrane. Reduced vasoactive intestinal peptide (VIP) levels and elevated SP levels observed in the colonic mucosa of IBD by using immunohistochemistry and immunoassay. This literature review aims to find out the correlations between the level of substance P (SP) and disease activity. We conducted a literature review on IBD, SP, and we searched PubMed and Google Scholar for relevant articles in English. The result of the study supports a positive relationship between the level of substance P (SP) and disease activity, with increased concentration of substance p in the colon and rectum of CD and UC patients. It is concluded that patients with active CD, along with inflammatory changes, had elevated plasma SP levels and immunoreactivity of SP in the colon than those seen in control and inactive cases. These alterations are more prevalent in ulcerative colitis than Crohn's disease and are more prevalent in the moderately infected area than the least affected area of the intestine.

Neurogenic tachykinin mechanisms in experimental nephritis of rats

We demonstrated earlier that renal afferent pathways combine very likely “classical” neural signal transduction to the central nervous system and a substance P (SP)–dependent mechanism to control sympathetic activity. SP content of afferent sensory neurons is known to mediate neurogenic inflammation upon release. We tested the hypothesis that alterations in SP-dependent mechanisms of renal innervation contribute to experimental nephritis. Nephritis was induced by OX-7 antibodies in rats, 6 days later instrumented for recording of blood pressure (BP), heart rate (HR), drug administration, and intrarenal administration (IRA) of the TRPV1 agonist capsaicin to stimulate afferent renal nerve pathways containing SP and electrodes for renal sympathetic nerve activity (RSNA). The presence of the SP receptor NK-1 on renal immune cells was assessed by FACS. IRA capsaicin decreased RSNA from 62.4 ± 5.1 to 21.6 ± 1.5 mV s (*p < 0.05) in controls, a response impaired in nephritis. Suppressed RSNA transiently but completely recovered after systemic administration of a neurokinin 1 (NK1-R) blocker. NK-1 receptors occurred mainly on CD11+ dendritic cells (DCs). An enhanced frequency of CD11c+NK1R+ cell, NK-1 receptor+ macrophages, and DCs was assessed in nephritis. Administration of the NK-1R antagonist aprepitant during nephritis reduced CD11c+NK1R+ cells, macrophage infiltration, renal expression of chemokines, and markers of sclerosis. Hence, SP promoted renal inflammation by weakening sympathoinhibitory mechanisms, while at the same time, substance SP released intrarenally from afferent nerve fibers aggravated immunological processes i.e. by the recruitment of DCs.

Administration of acetylsalicylic acid after parturition in lactating dairy cows under certified organic management: Part II. Biomarkers of nociception, inflammation, and stress

The objective was to assess the effect of oral administration of acetylsalicylic acid after calving on the concentrations of substance P (SP), haptoglobin (HP), and cortisol in lactating dairy cows. Holstein dairy cows (n = 152) from 3 organic herds were included. At parturition, cows were blocked by parity [multiparous (MULT) and primiparous (PRIM)] and calving ease [eutocia (EUT) and dystocia (DYS)] and were randomly assigned to 1 of 2 treatment groups: aspirin (ASP; n = 76), in which within 12 h after parturition cows received 4 treatments with acetylsalicylic acid (100 mg/kg; 2 boluses) at 12-h intervals, or placebo (PLC; n = 76), in which within 12 h after parturition cows received 4 consecutive treatments with gelatin capsules (2 capsules) containing water 12 h apart. Blood samples were collected immediately before treatment and at 12, 24, 36, 48, and 168 h (7 DIM) for assessment of circulating concentration of SP, HP, and cortisol. Based on farm records, cows were classified in the following clinical disease categories: no clinical disease event (NO-EVT), a single clinical disease event (SI-EVT), and more than 1 clinical disease event (MU-EVT). The study data were analyzed as a randomized complete block design using mixed multiple linear and logistic regression models. With regard to HP, there was a tendency for an interaction between treatment and parity, where MULT cows treated with ASP had lower concentration of HP compared with MULT cows treated with PLC (ASP = 124.33 ± 6.83 µg/mL; PLC = 143.9 ± 7.24 µg/mL). Analysis by calving ease showed that cows with DYS had higher concentrations of HP (DYS = 159.17 ± 5.97 µg/mL; EUT = 138.72 ± 6.22 µg/mL) and SP (only at 168 h; DYS = 64.99 pg/mL, 95% confidence interval, CI: 2.68-2.81; EUT = 60.33 pg/mL, 95% CI: 2.91-3.06) after calving compared with EUT cows. Regardless of treatment, PRIM cows had higher concentrations of SP (MULT = 55.11 pg/mL, 95% CI: 1.27-1.30; PRIM = 57.62 pg/mL, 95% CI: 1.99-2.06), HP (MULT = 134.14 ± 4.96 µg/mL; PRIM = 163.75 ± 7.76 µg/mL), and cortisol (MULT = 18.65 µg/mL, 95% CI: 1.02-1.05; PRIM = 21.92 µg/mL, 95% CI: 1.67-1.74) compared with MULT cows. In addition, cows that experienced SI-EVT or MU-EVT had higher concentrations of HP (NO-EVT = 134.13 ± 5.95 µg/mL; SI-EVT = 142.68 ± 7.32 µg/mL; MU-EVT = 170.03 ± 9.42 µg/mL) and cortisol (NO-EVT = 17.86 µg/mL, 95% CI: 1.20-1.24; SI-EVT = 21.01 µg/mL, 95% CI: 1.61-1.67; MU-EVT = 22.01 µg/mL, 95% CI: 2.08-2.18) compared with cows with NO-EVT recorded. Results from this study suggest that a short-duration anti-inflammatory therapy after calving reduced HP in MULT cows but may not have effects on SP and cortisol concentrations. Calving ease and parity affected the concentrations of markers of inflammation, nociception, and stress regardless of treatment. Further research is warranted to assess anti-inflammatory strategies aimed at decreasing inflammation and stress in DYS and PRIM cows and therefore improve welfare and performance of these high-priority groups.

Effects of estrogen and progesterone on the neurogenic inflammatory neuropeptides: implications for gender differences in migraine.

Neurogenic inflammation including calcitonin gene-related peptide (CGRP) and substance-P (SP) release plays a pivotal role in migraine pathogenesis. Prevalence of migraine is ~ 3 folds higher in women than in men, but its underlying mechanisms remained unclear. We investigated the effects of female sex hormones estrogen and progesterone on CGRP and SP in in-vivo and ex-vivo in rats of both sexes. For in-vivo experiments, male, female and ovariectomized rats were separated into four groups (n = 7) as control, estrogen, progesterone and estrogen + progesterone, respectively. Groups received daily intraperitoneal vehicle, 17β-estradiol, progesterone and 17β-estradiol + progesterone for 5days, respectively. For ex-vivo experiments in both sexes, isolated trigeminal ganglia and hemiskull preparations were divided into four groups (n = 6 or 8), respectively, as in-vivo groups, and administered the same test substances. CGRP and SP contents in plasma and superfusates were determined using ELISA. In in-vivo experiments, 17β-estradiol decreased CGRP levels in males and SP levels in ovariectomized rats. Progesterone increased both CGRP and SP levels in females. Their combination decreased both CGRP and SP levels in males, and only SP levels in ovariectomized rats. In ex-vivo experiments, 17β-estradiol reduced CGRP release in males and SP release in females in trigeminal ganglia. While progesterone increased CGRP release in trigeminal ganglia, it reduced SP release from hemiskulls in both sexes. Their combination restored progesterone-mediated changes in neuropeptides releases in both trigeminal ganglia and hemiskulls in both sexes. Estrogen alleviates neurogenic inflammation through modulation of CGRP and SP release. Progesterone has dual effects on these neuropeptides in different sites associated with migraine pain.

Pain May Promote Tumor Progression via Substance P-Dependent Modulation of Toll-like Receptor-4.

In a previous study, persistent pain was suggested to be a risk factor for tumor patients. However, the mechanism underlying this phenomenon is still unclear. Substance P (SP), a pain-related neuropeptide secreted by the neural system and the immune system, plays an important role in the induction and maintenance of persistent pain. In this study, in order to explore whether SP participates in the influence of pain on tumor progression, the serum samples of lung cancer and breast cancer patients were collected and tested. An elevated expression of SP was found in patients with pain. Cell pharmacological experiments revealed that SP can upregulate the expression of Toll-like receptor-4 (TLR-4) in tumor cells and increase the proliferation, migration, and invasive activity of tumor cells. As high expression of TLR-4 has the ability to enhance the biological activity of tumor cells, TLR-4 is thought to be involved in SP-induced tumor proliferation, migration, and invasion. Treatment of tumor cells with Aprepitant, a specific blocker of the NK-1 receptor, could reduce the expression of TLR-4 and reduce the proliferation, invasion, and migration activities of tumor cells; further proof of the influence of SP on TLR-4 expression depends on the NK-1 receptor located in tumor cells. Based on the results above, we proposed a possible mechanism underlying pain affecting tumor progression: The presence of pain increases the content of SP in patients' blood, and elevated SP increases the expression of tumor TLR-4 by acting on the NK-1 receptor, which ultimately affects the biological activity of the tumor.

Interleukin 25, thymic stromal lymphopoietin and house dust mites in pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the world. It is characterized by recurrent eczematous skin lesions, fluctuating course and chronic pruritus. Increasing evidence suggest that AD is more common in adults than previously thought. The disease is characterized by an impaired skin barrier, aberrant Th2-type cytokine production and intensive pruritus. Epithelial keratinocytes constitute the first physical, chemical and immunological barrier, classified as a part of the innate defense system. These keratinocytes secrete various factors, e.g. alarmins such as thymic stromal lymphopoietin (TSLP) and interleukin 25 (IL-25). Serum levels of substance P (SP) have been reported to be increased in patients with AD and correlated with itch intensity. Several previous studies reported a positive association between AD severity and house dust mites (HDM) sensitization. The aim of the study was to analyze IL-25, TSLP and SP concentrations in blood serum of adult patients with severe AD, depending on the degree of allergy to HDM. There were 31 adult AD patients enrolled into the study and a control group that consisted of 20 healthy subjects. AD was diagnosed on the basis of Hanifin and Rajka criteria. SCORing Atopic Dermatitis (SCORAD) and visual analogue (VAS) scores were used to assess the intensity of pruritus and blood content of specific IgE to HDM, as well as TSLP, IL-25 cytokines and SP was measured. Our study presents the evidence that IL-25 serum concentration is increased in patients with atopic dermatitis and this cytokine plays an important role in pathogenesis of this disease. HDM could stimulate the release of IL-25 which aggravates the disease severity. Our results corroborate previous findings on the role of TSLP in atopic dermatitis.

Low-dose capsaicin (0.01 mM) nasal spray is equally effective as the current standard treatment for idiopathic rhinitis: A randomized, double-blind, placebo-controlled trial

Low-dose capsaicin (0.01 mM) nasal spray is equally effective as the current standard treatment for idiopathic rhinitis: A randomized, double-blind, placebo-controlled trial

Effect of moxibustion on respiratory function and cutaneous histamine and neuropeptide contents of "Feishu" (BL13) in asthmatic rats

To observe the effect of moxibustion on respiratory function and contents of histamine and neuropeptides in skin tissue of "Feishu" (BL13) in asthmatic rats, so as to explore its mechanisms underlying improvement of asthma. Thirty-six SD rats were randomly divided into normal control, model and moxibustion groups, with 12 rats in each group. The asthma model was established by subcutaneous injection (at the back and groin, 0.5 mL) and i．p. injection (1 mL)of mixture solution of ovalbumin (OVA), Aluminium Hydroxide gel and 0.9% sodium chloride solution, and repeated nasal drip of 1% OVA. Moxibustion was applied to bilateral BL13 for 15 min, once daily for 14 days. The inspiratory and expiratory resistance, and pulmonary ventilation compliance were detected by using a small animal pulmonary function tester under anesthesia. The contents of histamine, vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in the local skin tissue of the left BL13 were assayed by using enzyme-linked immunosorbent assay (ELISA). After modeling, the inspiratory and expiratory resistance were significantly increased (P<0.01), and the lung ventilation compliance was significantly decreased in the model group relevant to the normal control group (P<0.01). Outcomes of ELISA showed that the content of VIP was significantly lower (P<0.01), and those of histamine, SP and CGRP in the skin of left BL13 were significantly increased in the model group relevant to the normal control group (P<0.01). Following the intervention, the inspiratory and expiratory resis-tance, cutaneous histamine, SP and CGRP contents were significantly decreased (P<0.01), while the lung ventilation compliance and cutaneous VIP level were significantly increased in the moxibustion group in contrast to the model group (P<0.01, P<0.05). Moxibustion of BL13 can improve pulmonary function in asthma rats, which may be related to changes of levels of histamine and neuropeptides as VIP, SP and CGRP in the local skin tissues of BL13.

Association of bovine uterine involution disturbances with serum neuropeptide concentrations.

Background and Aim:Puerperal diseases influence fertility and should be diagnosed as soon as possible. This study aimed to evaluate the applicability of serum concentrations of substance P (SP), vasoactive intestinal polypeptide (VIP), and interleukin (IL)1β in the early diagnosis of uterine involution disturbances.Materials and Methods:Blood serum samples of 86 dairy cows from six different farms were harvested within the first 20 days after calving from cows with uterine involution disturbances and healthy controls, respectively. Serum concentrations for SP, VIP, and IL-1β were determined using commercially available ELISA test kits. Statistical analyses included timely changes in blood serum levels and group comparisons of healthy cows and cows with uterine disease.Results:SP concentrations increased significantly within 20 days after calving (p<0.04) with no significant difference observed between the groups. Moreover, no significant differences were found between VIP and log IL-1β.Conclusion:Results showed that none of the examined serum parameters seems suitable as indicator of uterine involution disorders. Due to the timely changes in serum concentrations of SP after calving, a correlation to diseases might not be precluded. Further research is needed as regards the establishment of normative values concerning this parameter.

Metabolomic study of raw and bran-fried Atractylodis Rhizoma on rats with spleen deficiency

Atractylodis Rhizoma, a classical Chinese medicine, exhibits unambiguous therapeutic effect on spleen deficiency in China for decades. The aim of the present study was to explore the different effects on the composition and level of endogenous metabolites in rats with spleen deficiency after oral administration of raw and bran-fired Atractylodis Rhizoma, and to explain the mechanism of pharmacodynamic enhancement of the bran-fried Atractylodis Rhizoma from the perspective of metabolomics. With this purpose, spleen deficiency model was established by diet, excessive fatigue and bitter cold diarrhea. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of vasoactive intestinal peptide (VIP), Somatostatin (SS), substance P (SP) and succinodehydrogenase (SDH) in rats of each group, and to compare the contents of VIP, SS, SP and SDH among groups. UHPLC-Q-TOF-MS based metabolomics was adopted to analyze the plasma from spleen deficiency rats and control rats. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in rats among the control group and the model group；The OPLS-DA were used to analyze the effects of raw and bran-fried Atractylodis Rhizoma on the same metabolites. The results showed that compared with the control group, the contents of VIP, SS, SP and SDH in the plasma of model group decreased, which proved the success of the model group. Compared with model group, the contents of VIP, SS, SP and SDH in the plasma of raw and bran-fried Atractylodis Rhizoma increased, and the effect of bran-fried Atractylodis Rhizoma was better than that of raw Atractylodis Rhizoma. Metabolomics results showed that seventeen different metabolites of spleen deficiency were screened out in the plasma of rats with spleen deficiency compared with the control group. Among them, Nicotinic acid, Dihydrofolic acid, Pantetheine 4′-phosphate and Photophatidylcholine (PC) were the metabolites significantly associated with spleen deficiency, and bran-fried Atractylodis Rhizoma had better intervention and regulation. Through the analysis of metabolic pathways related to these different metabolites of spleen deficiency, and primarily involved in glucosamine metabolism, one carbon pool by folate and so on. This study showed that Atractylodis Rhizoma could provide satisfactory therapeutic effects on spleen deficiency and metabolomics study can be utilized to further understand the molecular mechanisms.

Observation on therapeutic effect and mechanism research of acupuncture on headache in the recovery phase of ischemic stroke

To explore the clinical therapeutic effect and mechanism of acupuncture on headache in the recovery phase of ischemic stroke. A total of 97 patients with headache in the recovery phase of ischemic stroke were randomized into an acupuncture group (57 cases) and a western medication group (40 cases). In the western medication group, flunarizine hydrochloride capsule was taken orally 5 mg each time, once a day. In the acupuncture group, acupuncture was applied at Qiuxu (GB 40), Zulinqi (GB 41), Xuanli (GB 6), Shuaigu (GB 8), Fengchi (GB 20) and Baihui (GV 20) for migraine; Chongyang (ST 42), Neiting (ST 44), Jiexi (ST 41), Zusanli (ST 36), Hegu (LI 4), Cuanzhu (BL 2) and Baihui (GV 20) for forehead pain; Jinggu (BL 64), Kunlun (BL 60), Tianzhu (BL 10), Fengchi (GB 20), Baihui (GV 20) and Sishencong (EX-HN 1) for occipital headache; Taichong (LR 3), Yongquan (KI 1), Sanyinjiao (SP 6), Fengchi (GB 20), Baihui (GV 20) and Sishencong (EX-HN 1) for parietal headache. The needles were retained for 30 min each time, once a day and 5 times a week. Both of the two groups were given consecutive treatment for 14 days. The visual analogue scale (VAS) and the headache scores before and after treatment and the recurrence rate 1 month after treatment were observed to evaluate the therapeutic effect, before and after treatment, the contents of substance P (SP), dopamine (DA), serotonin (5-HT), alpha-endorphin (α-EP) and beta-endorphin (β-EP) in plasma were determined by ELISA in the two groups. Compared before treatment, the VAS scores, the headache scores and the contents of SP, DA and 5-HT in plasma were reduced and the contents ofα-EP andβ-EP in plasma were increased in the two groups (all P<0.01). After treatment, the changes of the VAS score, the headache score and the contents of pain-related factors and endogenous opioid peptides in plasma in the acupuncture group were larger than the western medication group (all P<0.05). The total effective rate in the acupuncture group was 84.2% (48/57), which was superior to 62.5% (25/40) in the western medication group, and the recurrence rate in the acupuncture group was lower than the western medication group (both P<0.01). The therapeutic effect of acupuncture on headache in the recovery phase of ischemic stroke is superior to flunarizine hydrochloride capsule, and the mechanism may relate to down-regulate the pain-related factors and up-regulate endogenous opioid peptides in plasma.

Neurokinin-1 Receptor Antagonism Ameliorates Dry Eye Disease by Inhibiting Antigen-Presenting Cell Maturation and T Helper 17 Cell Activation

Neuroinflammation plays an important role in the pathogenesis of ocular surface disease, including dry eye disease (DED), but little is known about the contribution of substance P (SP) to DED. In this study, we investigated the expression of SP at the ocular surface and evaluated its effect on maturation of antigen-presenting cells (APCs), the key cell component involved in the induction of type 17 helper T-cell (Th17) response in DED. The effect of topical blockade of SP signaling was further investigated using neurokinin-1 receptor (NK1R) inhibitors on APC maturation, Th17 cell activation, and disease severity in a mouse model of DED. The results demonstrate that SP is constitutively expressed at the ocular surface, and trigeminal ganglion neurons are the major source of SP in DED. SP derived from trigeminal ganglion enhanced the expression of major histocompatibility complex class II maturation marker by bone marrow-derived dendritic cells, an effect that is abrogated by blockade of SP signaling using NK1R antagonist spantide. Finally, using a well-established murine model of DED, topical treatment of DED mice with NK1R antagonists CP-99,994 and L-733,060 suppressed APC acquisition of major histocompatibility complex class II, reduced Th17 cell activity, and ameliorated DED severity. These findings are of translational value, as they suggest that antagonizing NK1R-mediated SP signaling may be an effective strategy in suppressing Th17-mediated ocular surface disease.