Serum Substance P Levels Research Articles

Analyzing Substance Levels and Pain Perception in Painless Labor: The Impact of Spinal Epidural Analgesia.

Inflammation affects labor by influencing contractions and dilation. Pain, often linked to tissue ischemia, involves mediators like nitric oxide (NO), TNF-α, and substance P (SP). Neuraxial analgesia, including combined spinal epidural analgesia (SEA) with levobupivacaine, is preferred for its effectiveness and minimal side effects in painless labor. Understanding the impact of painless labor techniques on biomolecular processes such as NO, TNF-α, and substance P levels is crucial for improving pain management strategies. This study investigates these effects in parturients undergoing SEA with levobupivacaine, contributing to the development of novel pain medications and enhancing obstetric care. This experimental study, conducted at a General Hospital in Indonesia, involved 60 expectant mothers in labor or in the third trimester, expected to give birth vaginally at Permata Hati Metro Hospital. Blood serum was used for analysis, and serum NO, TNF-α, and SP levels were assessed using ELISA kit. There's a significant decrease in NO levels before and post-treatment in the SEA group compared to the control group (p < 0.05). However, no significant difference in TNF-α levels was observed between groups before and after treatment (p > 0.05). Additionally, there was no significant difference in SP levels between groups before treatment, but a significant difference was seen after treatment (p < 0.05). SEA significantly reduced labor pain compared to the control group (P < 0.05), with notable improvements in vital signs and APGAR scores, while also shortening labor duration (P < 0.001). In conclusion, SEA with levobupivacaine during painless labor reduces NO levels significantly and shows a trend of decreasing TNF-α and substance P levels, although not statistically significant, with clinical benefits for both patients and babies.

Molecular mechanism of residual lumbago and leg pain after transforaminal endoscopic treatment of lumbar disc herniation

To observe the residual of lumbago and leg pain with contained type （CT） and non-contained type （NCT） lumbar disc herniation （LDH） after transforaminal endoscopic treatment, and to explore the role of hypoxia-inducible factor-1α（HIF-1α） and transient receptor potential vanillate 1（TRPV1） pathway. A total of 68 single-segment LDH patients were selected from July 2021 to October 2022, including 44 males and 24 females；aged 26 to 67 years old with an average of（43.63±11.94） years old；course of disease was 4 to 36 （18.91±10.34） months；body mass index was （24.45±4.00） kg·m-2；there were 7 cases of L3,4 segments, 32 cases of L4,5 segments, and 29 cases of L5S1 segments. All of them were performed with percutaneous intervertebral endoscopic extraction of nucleus pulposus and were divided into contained group（CT group） and non-contained group （NCT group） with 34 cases respectively according to the integrity of outer layer of fibrous annulus observed during operation. A total of 17 patients who underwent open surgery for scoliosis or vertebral fracture were selected as control group, including 12 males and 5 females；aged 21 to 65 years old with an average of （39.41±12.80） years old；body mass index was （24.86±4.11） kg·m-2. The relative mRNA expression quantity of HIF-1α, TRPV1 in nucleus pulposus were measured by quantitative real-time PCR. The contents of neurokinin 1 receptor （NK1R）, nerve growth factor （NGF）, vascular endothelial growth factor （VEGF） in nucleus pulposus and the serum substance P （SP） and calcitonin gene-related peptide （CGRP） were detected by enzyme linked immunosorbent assay （ELISA）. The threshold of lumbar tenderness was detected by a pressure pain meter. The degree of lumbago and lumbar function were evaluated by visual analog scale （VAS） and Oswestry disability index （ODI） separately. The residual rate of postoperative lumbago and leg pain was assessed. The mRNA relative expression quantity of HIF-1α and TRPV1, and the contents of NK1R, NGF and VEGF in nucleus pulposus, and the levels of serum SP and CGRP before surgery in the NCT group were higher than those in the CT group（P<0.05）, and those in the CT group were higher than the control group（P<0.05）. At day 7 after surgery, the serum SP and CGRP levels, lumbago and leg pain VAS scores and lumbar ODI index in two LDH groups were lower than before surgery （P<0.05）, and those in the NCT group were higher than the CT group（P<0.05）, and the threshold of lumbar tenderness in the NCT group was lower than the CT group（P<0.05）. The differences of lumbago and leg pain VAS scores, lumbar ODI index and lumbar tenderness threshold between preoperative and postoperative 7 days in the NCT group were lower than those in the CT group（P<0.05）. The residual rate of lumbago and leg pain at 7 days after surgery in the NCT group was higher than that in the CT group（P<0.05）. HIF-1α and TRPV1 pathway promoted the excessive production of NGF, VEGF, NK1R in nucleus pulposus and serum neuropeptides SP and CGRP, which may lead to the higher residual rate of lumbago and leg pain with non-contained lumbar disc herniation postoperative.

Substance P Level in Patients with Degenerative Lumbar Spine Disorder undergoing Decompressive Surgery: An Observational Study

Introduction: Patients with degenerative lumbar spine disorders experience Chronic Low Back Pain (CLBP) for which they undergo decompressive surgery. Substance P (SP), a neurotransmitter which acts as a modulator of pain perception and transmits nociceptive signals via primary afferent fibers to the spinal cord and brainstem. In chronic painful conditions, SP level can be associated with the severity of pain and gets altered; however, this correlation is not present in acute pain. Aim: To evaluate serum SP level in CLBP patients undergoing decompressive spine surgery. Materials and Methods: The present study was a prospective observational study, in which 30 patients with CLBP undergoing decompressive spine surgery were enrolled. Along with them, one first-degree relative of each patient and an equal number of healthy volunteers were included in the study group. Patients were followed-up on the 5th postoperative day and at two months after surgery for the evaluation of SP levels and Visual Analogue Scale (VAS) scores. Statistical data analysis was carried out using IBM PASW Statistics (SPSS) 25.0 version software. SP levels followed a non normal distribution and were compared by Mann-Whitney U or Kruskal Wallis test (for 2 or more groups, respectively) and correlated using Spearman rank correlation. Results: Patients undergoing decompressive spine surgery had a significantly higher SP level (97.5 picogram/mL (pg/mL)) than healthy volunteers (23.22 pg/mL), p-value &lt;0.001. The serum SP levels in patients were found to be significantly reduced on the 5th postoperative day (31.7 pg/mL) and at two months after surgery (48.5 pg/mL), p-value=0.043. In contrast, there was no discernible change in the VAS score, which did not correlate with the fall in SP levels on the 5th postoperative day. Conclusion: SP level was elevated in subjects with degenerative lumbar spine disorders undergoing decompressive surgery. Higher levels of SP can be attributed to CLBP in those patients. SP can be contemplated as a biomarker of pain due to degenerative lumbar spine pathology. However, further studies are warranted to substantiate this.

Role of Substance P in Regulating Micro-Milieu of Inflammation in Alopecia Areata.

BackgroundAlopecia areata (AA) is an autoimmune disease characterized by chronic inflammation, the pathogenesis of which is unknown. Stress is believed to play a role; however, evidence remains insufficient. A recent study showed that substance P (SP) damaged hair follicles by causing neurogenic inflammation, activating perifollicular mast cells, and inducing keratinocyte apoptosis.ObjectiveWe aimed at studying the role of SP in AA pathogenesis. We investigated the SP levels in the lesional scalp tissues and serum. We also studied the effect of SP on the inflammatory response and hair growth in the outer root sheath (ORS) cells.MethodsWe compared the serum levels of SP in 58 AA patients and 28 healthy subjects. Then, we checked the expression of SP and SP receptor, neurokinin-1 receptor (NK-1R) in the scalps of AA patients and healthy controls using immunohistochemical staining. Finally, we analyzed the mRNA expression of inflammatory cytokines and hair growth-related factors in ORS cells.ResultsSP and NK-1R expression were markedly higher in the hair follicles and interfollicular epidermis of the scalp lesions of AA patients. However, there was no statistically significant difference in serum SP levels between controls and patients, regardless of the type of alopecia. SP significantly increased the mRNA expression of inflammatory cytokines and decreased hair growth-related growth factors in ORS cells, but the results were not dramatic.ConclusionSP triggered a localized micro-inflammation in lesional hair follicles, provoked an inflammatory response, and inhibited hair growth, thereby confirming the pathogenic role of SP in AA.

CD4+/IL‑4+ lymphocytes of the lamina propria and substance P promote colonic protection during acute stress.

Life stress may influence symptom onset and severity in certain gastrointestinal disorders in association with a dysregulated intestinal barrier. It has been widely accepted that stress triggers the hypothalamus-pituitary-adrenal (HPA) axis, releasing corticosterone, which promotes intestinal permeability. In response, colonic inflammation alters mucosal immune homeostasis and destroys the colonic architecture, leading to severe intestinal diseases. Endogenous substance P (SP) does not inhibit the initial extent of the HPA axis response to restraint stress, but it reduces the duration of the stress, suggesting that SP plays an important role in the transition between acute and chronic stress. The present study aimed to investigate the effect of two groups of mice exposed to stress, including acute and chronic stress. The corticosterone was evaluated by ELISA, colon samples were obtained to detected polymorphonuclear cells by hematoxylin and eosin staining, goblet and mast cells were identified by immunocytochemistry and cytokine-producing CD4+ T cells were analyzed by flow cytometry assays, adhesion proteins in the colon epithelium by western blotting and serum SP levels by ELISA. The results demonstrated an increase in the number of polymorphonuclear, goblet and mast cells, a decrease in claudin-1 expression and an elevation in E-cadherin expression during acute stress. Increased E-cadherin expression was also detected during chronic stress. Moreover, it was found that acute stress caused a shift towards a predominantly anti-inflammatory immune response (T helper 2 cells), as shown by the increase in the percentage of CD4+/IL-6+ and CD4+/IL4+ lymphocytes in the lamina propria and the increase in serum SP. In conclusion, this response promoted colonic protection during acute stress.

Substance P-induced lung inflammation in mice is mast cell dependent.

Allergic asthma is a common inflammatory lung disease and a major health problem worldwide. Mast cells (MCs) play a key role in the early-stage pathophysiology of allergic asthma. Substance P (SP) functions in neurogenic inflammation by activating MCs, and therefore, it may to participate in the occurrence and development of asthma. We examined the relationship between SP and lung inflammation, and also whether SP can directly trigger asthma. We measured the number of peripheral blood eosinophils, neutrophils and basophils and evaluated the levels of IgE and SP in blood samples of 86 individuals with allergic asthma. Serum IgE and SP levels were also determined in 29 healthy individuals. C57BL/6 mice were subjected to different doses of SP, and bronchoalveolar lavage fluid (BALF) was collected to count the inflammatory cells. Lung tissues were analysed using histopathological methods to evaluate lung peribronchial inflammation, fibrosis and glycogen deposition. Levels of IgE, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-13, IL-17 and IFN-γ were determined in mouse serum. Substance P levels were increased in the serum samples of patients with asthma. SP induced mouse lung peribronchial inflammation, fibrosis and glycogen deposition, with high levels of Th2-related cytokines such as IL-4, IL-5 and IL-13 observed in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kitW-sh/W-sh mice. Substance P levels increased significantly in serum of asthmatic patients and independently associated with the risk of asthma. Furthermore, SP induced Th2 lung inflammation in mice, which was dependent on MCs.

ZHU Lian's type-Ⅰ inhibition acupuncture combined with Zhuang medicinal thread moxibustion for acute herpes zoster

To observe the clinical efficacy of ZHU Lian's type-Ⅰ inhibition acupuncture combined with Zhuang medicinal thread moxibustion for acute herpes zoster (HZ), and explore the possible analgesic mechanism. Sixty-six patients with acute HZ were randomly divided into an observation group (33 cases, 1 case dropped off) and a control group (33 cases, 1 case dropped off). The patients in the control group were treated with valaciclovir hydrochloride tablets, mecobalamin tablets and vitamin B1 tablets for 14 days. The patients in the observation group were treated with ZHU Lian's type-Ⅰ inhibition acupuncture and Zhuang medicinal thread moxibustion. ZHU Lian's type-Ⅰ inhibition acupuncture was given at ashi points (around herpes site), Qimen (LR 14), Geshu (BL 17), Quchi (LI 11), Xuehai (SP 10) and Neiguan (PC 6); Zhuang medicinal thread moxibustion was given at Changzi point, Kuihua point, Xionglongji point, Zhuang medicine Jiaji points; both the treatment was given once every other day for 14 days. The symptom improvement (blister stopping time, scab forming time, scab removing time) in the two groups were observed. The pain visual analogue scale (VAS) score and serum levels of interleukin (IL)-6, IL-8, substance P (SP) in the two groups before and after treatment were compared. The clinical efficacy of the two groups and the recurrence rate of neuralgia 1, 2, 3 months after treatment were evaluated. The blister stopping time, scab forming time and scab removing time in the observation group were earlier than those in the control group (P<0.05). Compared before treatment, VAS scores and serum levels of IL-6, IL-8 and SP in the two groups were decreased after treatment (P<0.05), and those in the observation group were lower than those in the control group (P<0.05). The total effective rate in the observation group was 96.9% (31/32), which was higher than 84.4% (27/32) in the control group (P<0.05). The recurrence rates of neuralgia 1, 2, 3 months after treatment in the observation group were 9.7%, 6.5%, 3.2%, which were lower than 29.6%, 22.2%, 14.8% in the control group (P<0.05). The ZHU Lian's type-Ⅰ inhibition acupuncture combined with Zhuang medicinal thread moxibustion have better analgesic effect and lower recurrence rate of neuralgia in patients with acute HZ, and this effect might be related to the reduction of serum IL-6, IL-8 and SP levels.

Comparative efficacy and safety of Verbascox&lt;sup&gt;®&lt;/sup&gt; − a proprietary herbal extract capable of inhibiting human cyclooxygenase-2 − and celecoxib for knee osteoarthritis

The aim of this randomized, single-blind, active-controlled pilot study was to investigate the clinical efficacy of oral supplementation with Verbascox®, a proprietary herbal extract capable of inhibiting human cyclooxygenase-2 (COX-2), in patients with mild-to-moderate osteoarthritis (OA) of the knee. Patients in the control group (n = 50) did not undergo any treatment (watchful waiting). Patients in the Verbascox® group (n = 50) received oral supplementation (800 mg/day) with the herbal extract for 2 weeks. The final study group consisted of patients (n = 50) who received celecoxib, a known pharmacological inhibitor of COX-2, 200 mg/day for 2 weeks. Examining physicians and laboratory personnel were blinded to group assignment, whereas patients were unblinded. All participants were evaluated using standard measures of pain relief and improvement in functional capacity at baseline, after 1 week, and at the end of the 2-week treatment course. Moreover, serum levels of substance P (SP), a member of the tachykinin family of neuropeptides involved in pain perception, were measured at the three time points. Both Verbascox® and celecoxib reduced pain, improved functional capacity, and lowered serum SP levels at 2 weeks compared with baseline, without significant inter-arm differences. Both Verbascox® and celecoxib showed a limited number of treatment-emergent adverse events. In summary, oral supplementation with Verbascox® (800 mg/day) in patients with mild-to-moderate OA of the knee is as effective and safe as a standard therapeutic dose of celecoxib in terms of pain relief and improvement in functional capacity after a 2-week treatment course.

Clinical observation on heat-sensitive moxibustion plus lactulose for postoperative constipation of mixed hemorrhoid due to spleen deficiency

To observe the clinical effect of heat-sensitive moxibustion plus lactulose oral liquid for postoperative constipation of mixed hemorrhoid. A total of 70 patients were randomized into a treatment group and a control group, with 35 cases in each group by a random number table. Patients in the control group received lactulose oral liquid alone, while those in the treatment group received additional heat-sensitive moxibustion at Shenque (CV 8). The treatment was given once a day for 15 consecutive days. The defecation interval time, defecation duration, the scores of stool form, visual analog scale (VAS) and patient assessment of constipation quality of life questionnaire (PAC-QOL), as well as the serum substance P (SP) and nitric oxide (NO) levels were measured before and after treatment. After treatment, the stool form score, defecation interval time and defecation duration in the two groups dropped significantly (all P<0.05), and they were lower in the treatment group than in the control group (all P<0.05). After treatment, the VAS scores in the two groups dropped significantly (both P<0.05), and it was lower in the treatment group than in the control group (P<0.05). After treatment, the PAC-QOL scores in the two groups dropped significantly (both P<0.05), and it was lower in the treatment group than in the control group (P<0.05). After treatment, the serum SP and NO levels in the two groups improved significantly (all P<0.05), and showed statistically significant differences between the treatment group and the control group (both P<0.05). Heat-sensitive moxibustion plus lactulose oral liquid can improve stool form, shorten defecation interval time and defecation duration, alleviate defecation pain, and improve quality of life (QOL) for patients with postoperative constipation of mixed hemorrhoid, which may be related to the regulation of the SP and NO levels.

Mental health and drug use severity: the role of substance P, neuropeptide Y, self-reported childhood history of trauma, parental bonding and current resiliency

Background Many risk factors lead to opioid use and drug-related problems. One of the challenges to understand behavioural factors, drug problems and psychopathology is to identify biological markers that are suitable for research on broad substance abuse and dependence involving human participants. Aims The study has examined the relationships between the self-reported childhood history of trauma, parental bonding, psychopathology, impulsivity, current resiliency, two neuropeptides, possible markers of behaviour and emotion regulation, and severity of drug-related problems. Methods One hundred and sixty-seven individuals with a history of opioid use completed questionnaires. Serum neuropeptide Y (NPY) and substance P (SP) levels were analysed. Moderating and mediating relationships between variables were examined using structural equation modelling (SEM). Results Antisocial features, depression, impulsivity, SP, NPY, emotional neglect and resilience are associated with severity of drug-related problems. SP is associated with antisocial personality traits. Conclusions The novelty of this study is the proposed possible link between biochemical markers, antisocial features and behavioural and emotional regulation. Serum NPY and SP levels have a potential to be used as a biomarker in opioid users before and in the treatment process to account for interactions between biological vulnerabilities and childhood risk factors in predicting behavioural adjustment and more severe drug-related problems.

Effects of an Extract of Salmon Milt on Symptoms and Serum TNF and Substance P in Patients With Fibromyalgia Syndrome

PurposeThe aim of this study was to evaluate the effects of a dietary supplement containing primarily an extract of salmon's milt (semen) on symptoms and blood levels of proinflammatory molecules in patients with fibromyalgia syndrome (FMS), a chronic, painful musculoskeletal disease without a distinct pathogenesis or treatment. We recently reported increased serum levels of the proinflammatory molecules substance P (SP) and tumor necrosis factor (TNF) in patients with FMS as compared to those in normal controls. MethodsThis prospective, open-label study was conducted in patients with FMS (n = 87; 80 women, 7 men; age range, 18–80 years) selected from 2 clinical centers in Spain. Patients were administered the supplement and were evaluated at weeks 1 (before treatment), 4, 8, and 12 (end of treatment) for clinical parameters of functioning, fatigue, and pain, as well as overall impression. Patients were directed to take 1 capsule per day in the morning for the first 4 weeks, followed by 1 capsule in the morning and 1 capsule in the evening for the remaining 8 weeks. Differences in symptom scores in patients with FMS between weeks 1 and weeks 4, 8, and 12 were evaluated using ANOVA. Blood was obtained and serum separated in patients with FMS at 1 and 12 weeks and in a separate population of healthy controls (n = 20; 15 women, 5 men; age range, 25–65 years). Serum levels of SP and TNF were measured in patients with FMS at 1 and 12 weeks and in healthy controls by ELISA. TNF and SP levels in patients with FMS were compared between weeks 1 and 12, as well as between patients with FMS and untreated controls, using the Mann–Whitney U test. FindingsClinical parameters of functioning, fatigue, and pain, as well as overall impression, were improved significantly at 4 weeks as compared to 1 week and remained unchanged for the duration of the study (all, P < 0.0001). Serum TNF and SP levels were significantly elevated at 1 week in patients with FMS compared to controls and were decreased significantly at 12 weeks as compared to 1 week (all, P < 0.0001). ImplicationsOur findings indicate that this dietary supplement may significantly improve symptoms in patients with FMS. This is the first time to our knowledge that any molecule has been reported to be associated with a reduction in serum SP level. Consequently, the supplement or its hypothesized main active ingredient, spermine, may be developed as a novel treatment approach to FMS or other neuroinflammatory conditions. ClinicalTrials.gov identifier: NCT03911882.

Determining the Temporal Profile of Intracranial Pressure Changes Following Transient Stroke in an Ovine Model.

Background and PurposeCerebral edema and elevated intracranial pressure (ICP) are the leading cause of death in the first week following stroke. Despite this, current treatments are limited and fail to address the underlying mechanisms of swelling, highlighting the need for targeted treatments. When screening promising novel agents, it is essential to use clinically relevant large animal models to increase the likelihood of successful clinical translation. As such, we sought to develop a survival model of transient middle cerebral artery occlusion (tMCAO) in the sheep and subsequently characterize the temporal profile of cerebral edema and elevated ICP following stroke in this novel, clinically relevant model.MethodsMerino-sheep (27M;31F) were anesthetized and subject to 2 h tMCAO with reperfusion or sham surgery. Following surgery, animals were allowed to recover and returned to their home pens. At preselected times points ranging from 1 to 7 days post-stroke, animals were re-anesthetized, ICP measured for 4 h, followed by imaging with MRI to determine cerebral edema, midline shift and infarct volume (FLAIR, T2 and DWI). Animals were subsequently euthanized and their brain removed for immunohistochemical analysis. Serum and cerebrospinal fluid samples were also collected and analyzed for substance P (SP) using ELISA.ResultsIntracranial pressure and MRI scans were normal in sham animals. Following stroke, ICP rose gradually over time and by 5 days was significantly (p < 0.0001) elevated above sham levels. Profound cerebral edema was observed as early as 2 days post-stroke and continued to evolve out to 6 days, resulting in significant midline shift which was most prominent at 5 days post-stroke (p < 0.01), in keeping with increasing ICP. Serum SP levels were significantly elevated (p < 0.01) by 7 days post-tMCAO.ConclusionWe have successfully developed a survival model of ovine tMCAO and characterized the temporal profile of ICP. Peak ICP elevation, cerebral edema and midline shift occurred at days 5–6 following stroke, accompanied by an elevation in serum SP. Our findings suggest that novel therapeutic agents screened in this model targeting cerebral edema and elevated ICP would most likely be effective when administered prior to 5 days, or as early as possible following stroke onset.

Serum substance P and vasoactive intestinal peptide levels in infants with acute intussusception.

ObjectiveWe aimed to investigate the role of the intestinal neurotransmitters vasoactive intestinal peptide (VIP) and substance P (SP) at different time points in infants with acute intussusception.MethodsThirty patients who were diagnosed with acute intussusception were enrolled in the study and classified as the experimental group. Another 30 patients with an indirect inguinal hernia who had no intestinal injury were included as the control group. Serum SP and VIP levels at different time points, including pre- and postoperation, were detected by enzyme-linked immunosorbent assay and compared between the two groups.ResultsSerum SP levels in patients with acute intussusception were significantly higher than those in controls. However, with recovery of acute intussusception, SP levels gradually decreased after treatment. Serum VIP levels in patients with acute intussusception were significantly lower than those in controls. However, with recovery of acute intussusception, VIP levels gradually increased after treatment.ConclusionsSP and VIP levels may have a potential relationship with the pathogenetic process of intussusception.

Relationship with excessive daytime sleepiness and serum substance P levels in OSAS patients and the effect of PAP treatment

Obstructive sleep apnea syndrome (OSAS) is a commonly seen disorder characterized by repeated episodes of upper airway obstruction during sleep leading to intermittent hypoxemia or arousal. We aim to evaluate the effects of positive airway pressure (PAP) treatment on daytime sleepiness and serum Substance P (SP) levels in OSAS patients. Seventy-one consecutive patients with newly diagnosed OSAS and 19 non-apneic control subjects were enrolled to the study. PAP treatment indicated subjects were re-evaluated after 3 months of treatment. Morning SP levels of OSAS patients and Epworth sleepiness scale (ESS) were assessed at the beginning and then after 3 months of PAP treatment. Of the patients 71 (78.9%) were male and 19 (21.1%) were female, with a median age of 45 [20–62]. The levels of SP in the OSAS group were significantly lower than the snorer group and a significant correlation was not found between serum levels of SP and ESS. SP levels were negatively correlated with AHI. The baseline SP median was 336.1 pg/mL [121.6–536.1], while the 3rd month SP median was 213.1 pg/mL [103.5–727.6]. Serum SP values were found to have significantly decreased at 3 months (p < 0.0001). Statistically significant correlation was not found between percentage of ESS change and the percentage of SP change. It can be assumed that the SP level is reduced as part of the compensation mechanism in OSAS cases and supporting this mechanism, the PAP therapy further reduces the SP value by relieving the cases from apnea and the intermittent hypoxia burden.

Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in breast cancer.

Breast cancer is the second leading cause of cancer death in women with increasing incidence. Hence, finding a diagnostic factor and/or potential drug target could lead to an earlier diagnosis or a more effective therapeutic protocol. It is shown that substance P (SP) through its receptor neurokinin-1 (NK1R) could initiate tumor cell proliferation, angiogenesis, and migration. This was a case-control study on 41 women with breast cancer and 34 healthy controls. Serum level of SP was measured using an ELISA method, and immunohistochemistry staining was performed to study NK1R expression in different cell compartments. Assessing serum SP values of patients showed significantly higher levels than those of healthy individuals. However, no significant correlation was found between SP levels and tumor criteria, but between SP and HER-2. Moreover, the percentage, intensity of staining as well as tissue distribution of NK1R were significantly higher in tumor tissues as compared with controls. Increased serum SP levels and NK1R tissue distribution were observed in patients with breast cancer as compared with their controls, highlighting the involvement of SP/NK1R complex in breast cancer incidence. NK1R profound expression in tumor cell cytoplasm and its significant correlation with the majority of cancer features can be of importance to be taken into consideration as a possible potential therapeutic target in future targeted therapeutic strategies. Furthermore, cytoplasmic expression of NK1R can be suggested as a potent prognostic factor as it has shown significant correlation with TNM and tumor grade.

Increased levels of substance P in patients taking beta-blockers are linked with a protective effect on oropharyngeal dysphagia.

We have recently found a potential protective effect of beta-blockers on oropharyngeal dysphagia (OD). The action mechanism by which beta-blockers could wield this protective effect is unknown, but the neurotransmitter substance P (SP) could play a key role. The aim of this study was to analyze serum and saliva SP levels in patients taking beta-blockers (TBB), and to explore its relationship with OD. Adult (>50year) patients TBB were randomly recruited from the primary care setting and 1:1 matched by age, sex, and Barthel Index (BI) with patients not taking beta-blockers (NTBB). Serum and saliva samples were taken and analyzed for their SP levels using an enzyme-linked immunosorbent assay (ELISA). Socio-demographic and clinical variables were collected. Dysphagia was evaluated in all patients using the clinical volume-viscosity swallow test (V-VST). We studied 28 patients TBB (64.96±7.31years, 57.1% women, BI 99.6±1.31, carvedilol-equivalent dose 24.11±18.12mg) and 28 patients NTBB (65.61±6.43years, 57.1% women, BI 99.6±1.31). SP serum levels were significantly higher in patients TBB (260.68±144.27 vs 175.46±108.36pg/mL, P=.009) as were SP saliva levels (170.34±146.48 vs 102.73±52.28pg/mL, P<.001) compared with patients NTBB. The prevalence of OD was 32.1% in patients TBB and 67.9% in patients NTBB (P=.015). Moreover, patients with OD had significantly lower SP saliva levels in comparison with patients without clinical signs of OD (98.39±43.25 vs 174.69±147.21pg/mL) P<.001. We have found that serum and saliva SP levels are greater in patients TBB. This increase in SP levels could be the action mechanism by which beta-blockers protect patients from OD.

Transient Receptor Potential Ankyrin 1 and Substance P Mediate the Development of Gastric Mucosal Lesions in a Water Immersion Restraint Stress Rat Model

Background: Activation of substance P (SP) contributes to the development and maintenance of gastric lesions, but the mechanisms underlying the release of SP and SP-mediated damage to the gastric mucosa remain unknown. Transient receptor potential ankyrin 1 (TRPA1) is expressed in SP-positive neurons in the dorsal root ganglion (DRG) and stomach of rats. We hypothesized that water immersion restraint stress (WIRS) may activate and sensitize TRPA1 in DRG neurons, subsequently inducing the release of SP from DRG and stomach cells, causing the development of acute gastric mucosal lesions (AGML). Methods: Changes in TRPA1 and SP expression in T8–11 DRG sensory neurons and the stomach in an AGML rat model were determined by reverse transcription polymerase chain reaction, western blotting and immunohistochemistry. The SP levels of serum and gastric mucosa were measured by using an enzyme-linked immunosorbent assay (ELISA). Gastric lesions were evaluated by histopathological changes. The TRPA1 antagonist HC-030031 and TRPA1 agonists allyl isothiocyanate were used to verify effect of TRPA1 and SP on AGML. Results: SP and TRPA1 in the DRG and stomach were upregulated, and the serum and gastric mucosa levels of SP were increased after WIRS, which are closely associated with AGML. The release of SP was suppressed and AGML were alleviated following a selective TRPA1 antagonist HC-030031. TRPA1 agonists AITC increased release of SP and led to moderate gastric lesions. We confirmed that WIRS induced the release of SP in the DRG, stomach, serum and gastric mucosa, and in a TRPA1-dependent manner. Conclusions: Upregulated SP and TRPA1 in the DRG and stomach and increased serum and gastric mucosa SP levels may contribute to stress-induced AGML. TRPA1 is a potential drug target to reduce stress-induced AGML development in patients with acute critical illnesses. This study may contribute to the discovery of drugs for AGML treatment.

Serum substance P: an indicator of disease activity and subclinical inflammation in rheumatoid arthritis.

The aim of the is study is to examine the role of serum substance P (SP) levels as a simple biomarker for rheumatoid arthritis (RA) disease activity, its correlation with other markers of disease activity, and with selected clinical parameters. The study comprised 90 RA patients and 24 healthy controls. RA activity was assessed by means of the disease activity 28-C-reactive protein (DAS28-CRP) index and ultrasound power Doppler (USPD) by the German ultrasound score based on seven joints. SP serum values were obtained by means of an ELISA commercial kit. Statistics were achieved by the Student's t test and Spearman correlation analysis with Bonferroni correction. As a group, RA patients had significantly increased levels of SP compared with healthy controls (p < 0.0001). SP levels correlated with DAS28-CRP (r= 0.5050, p < 0.0001), number of tender joints (NTJ, r= 0.4668, p < 0.0001), number of swollen joints (NSJ, r = 0.4439, p < 0.0001), visual analogue scale (VAS, r = 0.5131, p < 0.0001). However, SP did not correlate with CRP levels (r = 0.0468, p = 0.6613), nor with the USPD (r = 0.1740, p = 0.1009). Elevated serum SP is a common feature of RA patients, which also appears to correlate with clinical measurements of disease activity and with subjective clinical data (NTJ and VAS). Thus, although SP is higher in RA patients with high disease activity, it also detects subtle RA disease activity even in patients in apparent remission, which suggests its usefulness for therapeutic decisions.

Effects of Acupuncture Treatment on Fibromyalgia Symptoms, Serotonin, and Substance P Levels: A Randomized Sham and Placebo-Controlled Clinical Trial.

The aim of this study was to evaluate the effects of acupuncture treatment on serum levels of serotonin and substance P (SP) as well as on clinical parameters in patients with fibromyalgia (FM). This is a randomized controlled clinical trial. Seventy-five women with FM were randomized into one of three kinds of acupuncture treatment: real acupuncture group (AcG), sham acupuncture group (ShG), and simulated acupuncture group (SiG). Treatments were applied semiweekly for four weeks. The serum levels of serotonin and SP were evaluated before and after the eight sessions. Patients were clinically assessed by visual analog scale (VAS), the number of tender points (NTP), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), and Nottingham Health Profile (NHP) at baseline, after the last treatment, and one and three months after completion of all treatments. Serum serotonin values increased significantly after treatment in AcG and ShG (P < 0.001 and P < 0.01, respectively). The increase in the AcG was also different from both of the other groups (P < 0.01). While SP levels decreased in the AcG, they increased in the SiG (P = 0.001). In the AcG, significant improvements were found in almost all clinical outcomes after treatment. These usually continued for three months. In the ShG, there were also significant changes on the NTP, VAS, FIQ, and BDI scores after treatment. Improvements on the NTP and FIQ scores lasted for three months. In the SiG, significant improvements were found only in the NTP, VAS, and BDI scores after treatment. Acupuncture, rather than sham or placebo acupuncture, may lead to long-term improvements on clinical outcomes and pain neuromediator values. Changes in serum serotonin and SP levels may be a valuable explanation for acupuncture mechanisms in FM treatment.

Sustained Low Serum Substance P Levels in Non-Surviving Septic Patients.

Previously, researchers found higher serum substance P (SP) concentrations in survivors of severe sepsis than in non-survivors at the time of severe sepsis diagnosis. The objectives of our current study were to determine whether there is an association between serum SP levels during the first week and sepsis mortality, sepsis severity, serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10, and whether serum SP levels during the first week could be used as a biomarker of sepsis mortality. We determined serum concentration of SP, TNF-α, and IL-10 at days 1, 4, and 8. The end-point of the study was mortality at 30 days. We found that non-survivor (n = 104) compared to survivor patients (n = 206) showed lower serum SP levels at days 1, 4, and 8 (p < 0.001). Multiple logistic regression analyses showed an association between 30-day mortality and serum SP levels at days 1, 4, and 8 (p < 0.001) controlling for SOFA score, diabetes mellitus, age, and lactic acid levels. The most interesting findings of our study were that there is an association between serum SP levels during the first week and sepsis mortality, and that serum SP levels during the first week could be used as a biomarker of sepsis mortality.