Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Monoarthritis was induced in Lewis rats by interdermal injection in the left hind paw of a suspension of Mycobacterium tubercolusis in mineral oil (500 micrograms 100 microliters-1). Controls were injected with 100 microliters mineral oil. 2. Withdrawal latencies to thermal stimuli of the inflamed paw, the contralateral and both paws of control rats were measured at daily intervals after injection by the plantar test. 3. After detection of the pain threshold, rat spinal cords were removed and horizontal dorsal slices were mounted in a 3-compartment bath to measure electrically-evoked release of substance P-like immunoreactivity (SP-LI). 4. The inflamed paw of monoarthritic rats exhibited a lower pain threshold to thermal stimuli than the contralateral paw of the same animals and both paws of control rats. Inflamed paw hyperalgesia was maximal two days after injection, and declined gradually between 7 to 21 days with no evidence of excitability of withdrawal reflexes after 28 days. 5. During the 28 days study, monoarthritic rats gained less weight than control rats. 6. Electrical stimulation of the dorsal roots attached to rat isolated spinal cord slices induced a significant increase (174 +/- 18% of basal outflow which was 30.3 fmol 8 ml-1, n = 5) in SP-LI release. 7. One-week after induction of inflammation no differences in the amount of SP-LI released from the spinal cord of incomplete Freund's adjuvant-treated rats (IFA) and Freund's adjuvant-treated rats (CFA) were detected. Two weeks after, CFA spinal cord tended to release more SP-LI than IFA cords and, 21 days after injection, the spinal cord of CFA rats released significantly more peptide than IFA rats (17.8 +/- 2.8 fmol ml-1, n = 12 and 6.9 +/- 3.2 fmol ml-1, n = 9, respectively).8. Twenty-one days after treatment, the evoked release from monoarthritic rat spinal cords was increased by 263 + 42% (n = 3) in the presence of the GABAB receptor antagonist, CGP 36742 (100 micro M)which also significantly potentiated monoarthritis-induced hyperalgesia up to 45 min after injection(100 mgkg-1, i.p.).9. These findings may provide a basis for a novel approach to chronic pain therapy but also an explanation for the lack of analgesia produced by the GABAB agonist, baclofen, in chronic as compared to acute pain.
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PMID:Spinal cord SP release and hyperalgesia in monoarthritic rats: involvement of the GABAB receptor system. 753 91

1. The interaction between N-methyl-D-aspartate (NMDA) and NK1 tachykinin receptors was analyzed isobolographically in rats with inflammatory hyperalgesia induced by intraplantar injection of complete Freund's adjuvant-saline emulsion (CFA, 100 micrograms Mycobacterium tuberculosis). 2. Thermal hyperalgesia of the inflamed paw, determined by paw withdrawal response to a heat stimulus, was dose-dependently attenuated by intrathecal administration of an NMDA receptor antagonist, dextrorphan (2.5-40 micrograms, ED50 = 7.2 micrograms), and two NK1 tachykinin receptor antagonists, WIN 51,708 (0.01-200 micrograms, ED50 = 10.4 micrograms) or CP-96,345 (5-200 micrograms, ED50 = 82.1 micrograms). There was no effect of these agents on the nociceptive threshold of the non-inflamed paw. CP-96,344, an enantiomer of CP-96,345 that is inactive as an NK1 tachykinin receptor antagonist, slightly attenuated hyperalgesia at a dose of 200 micrograms. 3. Combinations of dextrorphan and WIN 51,708 were administered at fixed ratios (10%:90%; 41%:59%; 90%:10%). Isobolographic analysis revealed that the ED50s obtained from the three combination ratios were not significantly different from those that were expected from a simple additive effect. 4. Thus, an additive interaction was demonstrated between NMDA and NK1 tachykinin receptor systems at the spinal level. These results suggest that both NMDA and NK1 tachykinin receptors are activated in response to peripheral inflammation, but that they may contribute independently to development of hyperalgesia.
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PMID:An isobolographic analysis of the effects of N-methyl-D-aspartate and NK1 tachykinin receptor antagonists on inflammatory hyperalgesia in the rat. 882 63

In this study, Freund's adjuvant-induced monoarthritis in the rat hind paw was used to induce chronic pain and inflammation. In order to compare the basal outflow, electrically-evoked release and total content of calcitonin gene-related peptide like immunoreactivity (CGRP-LI) with previously reported changes in substance P (SP-LI), the lumbar enlargement of monoarthitic (complete Freund's adjuvant-treated, CFA rat) and control (incomplete Freund's adjuvant-treated, IFA rat) spinal cords were used. During the 4-wk period after injection, neither the basal nor the evoked release of CGRP-LI from CFA cords differed from controls. By contrast, we have previously reported that SP-LI release from CFA rat spinal cords was significantly higher than from controls, 21 days after inoculation with Freund's adjuvant. Electrically-evoked CGRP-LI release from 21-day CFA rat spinal cord slices was not modified by superfusion with a GABAB antagonist, CGP 36742 (100 microM) which could greatly increase SP-LI release. However, the release of both peptides was significantly increased to the same extent in IFA and normal tissue but to a lesser extent in CFA cords, by superfusion with the opioid antagonist naloxone (1 microM). In conclusion, CGRP-LI, unlike SP-LI, did not appear to be susceptible to any changes in the lumbar enlargement of the rat spinal cord during inflammation of the hind paw. In addition, CGRP-LI release was increased by antagonism of opiate but not GABAB receptors, suggesting that during chronic inflammation of one hind paw, the GABAB ergic system, unlike the opioid system, might be activated to selectively inhibit the enhanced SP-LI release but not CGRP-LI release which is not changed.
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PMID:Calcitonin gene-related peptide content, basal outflow and electrically-evoked release from monoarthritic rat spinal cord in vitro. 888 Aug 59

Inflammatory pain involves the sensitization of both primary afferent and spinal cord neurons. To explore the neurochemical changes that contribute to inflammatory pain, we have examined the expression and ligand-induced internalization of the substance P receptor (SPR) in the spinal cord in acute, short-term, and long-term inflammatory pain states. These inflammatory models included unilateral injection of formalin (8-60 min), carrageenan (3 hr), and complete Freund's adjuvant (CFA; 3 d) into the rat hindpaw as well as adjuvant-induced polyarthritis (21 d). In acute inflammatory pain there is ongoing release of substance P (SP) as measured by SPR internalization in lamina I neurons at both 8 and 60 min after formalin injection. Although there is no tonic release of SP in short-term inflammatory pain, at 3 hr after carrageenan injection, SP is released in response to both noxious and non-noxious somatosensory stimulation with SPR internalization being observed in neurons located in both laminae I and III-IV. In long-term inflammatory pain models (CFA and polyarthritis) the same pattern of SP release and SPR activation occurs as is observed in short-term inflammation with the addition that there is a significant upregulation of the SPR in lamina I neurons. These results suggest that SPR internalization might serve as a marker of the contribution of ongoing primary afferent input in acute and persistent pain states. These stereotypical neurochemical changes suggest that there are unique neurochemical signatures for acute, short-term, and long-term inflammatory pain.
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PMID:Spinal substance P receptor expression and internalization in acute, short-term, and long-term inflammatory pain states. 1046 Feb 73

Adjuvant-induced experimental arthritis (AA) was examined in adult male Lewis rats after isolated capsaicin (CAPS)-induced loss of small, nonmyelinated, afferent fibers in lymph nodes draining the site of adjuvant challenge. AA was induced by intradermal injection of Freund's complete adjuvant (CFA) into the subplantar area of the right hind paw. Controls received similar injections of mineral oil, the vehicle for CFA. One day later, half of the CFA-treated rats and half of the mineral oil-treated rats received injections of CAPS bilaterally into the draining lymph nodes (DLN). The DLN of remaining rats were injected with 50:50 ethanol/sterile physiological saline, the vehicle for CAPS. This paradigm resulted in four groups designated: CFA/CAPS, CFA/vehicle, vehicle/CAPS and vehicle/vehicle. Since substance P (SP) is present in small, nonmyelinated, afferent fibers, the target of the neurotoxin, CAPS, a radioimmunoassay specific for SP was used to verify the loss of these nerve fibers. CAPS injections into the DLN resulted in a loss in SP concentration in the DLN, with no depletion of SP in the spleen or sciatic nerve. These findings support the destruction of SP-containing nerves, which we interpret as verification of the selective loss of small, non-myelinated afferent nerves in the DLN with no significant spread of the neurotoxin to the nearby sciatic nerves which supply small, nonmyelinated, afferent fibers to the hind limb joints. Also, preservation of SP content in spleen indicates CAPS did not circulate via the lymphatic drainage. No chronic inflammation was observed in the fore or hind limbs from rats treated with the vehicle for CFA (vehicle/vehicle, vehicle/CAPS) at any time during the study. In CFA/vehicle-treated rats, bilateral, symmetrical inflammation of the hind limbs was apparent 14 days after challenge with CFA, and became progressively more inflamed through day 20. In contrast, hind limb inflammation in arthritic rats treated with CAPS was not symmetrical. On days 14 and 20 after challenge with CFA, the inflammatory response in the left hind limb, contralateral to the site of CFA injection, was significantly (p < 0.05) attenuated compared with the response seen on the right side of CFA/CAPS-treated rats, and with the response seen in left hind limb of CFA/vehicle-treated animals. In fact, the mean dorsoplantar width of contralateral hind limbs from CFA/CAPS-treated animals was not different from that measured in non-AA control groups. These findings support a role for small, nonmyelinated, sensory nerves that modulate immune responses in DLN in the development and progression of AA in Lewis rats.
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PMID:Local application of capsaicin into the draining lymph nodes attenuates expression of adjuvant-induced arthritis. 1075 99

Substance P (SP) has been widely studied as a mediator of nociception. The release of SP from primary afferent neurons is increased during nociception, and SP activates neurokinin-1 (NK-1) receptors in the spinal cord and periphery. Nociception-evoked alterations in NK-1 receptor gene expression have been studied in rat models of persistent pain but have not been characterized in any murine models of peripheral inflammation. This study assessed behavioral responses and NK-1 receptor mRNA gene expression in mice receiving formalin or Freund's complete adjuvant (CFA) as an inflammatory stimulus. Mechanical withdrawal thresholds were measured before injection of formalin or CFA and hind paw licking/biting timed during the late-phase of the formalin response. Two and 24 hours after formalin or CFA injection, mechanical withdrawal thresholds were measured and the mice euthanized. Solution hybridization-nuclease protection assays were used to quantify NK-1 receptor mRNA levels. Results demonstrated that inflamed hind paws were edematous, and the withdrawal thresholds of the inflamed hind paws were significantly lower after formalin or CFA injection. Neurokinin-1 receptor mRNA levels in the ipsilateral dorsal spinal cords of mice were higher at 24 h after formalin injection or 4 days after CFA injection. These results confirm that mice are hyperalgesic at late time points after formalin or adjuvant injection when NK-1 receptor gene expression is elevated in the dorsal spinal cord. This supports the hypothesis that increased NK-1 receptor gene expression contributes to the development and maintenance of a hyperalgesic state.
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PMID:Formalin- or adjuvant-induced peripheral inflammation increases neurokinin-1 receptor gene expression in the mouse. 1253 87

The development of the neurokinin-1 receptor-deficient (NK1R(-/-)) mouse permitted inquiry into the regulation of secretory immunoglobulin A (S-IgA) responses by substance P (SP) after oral immunization with a Salmonella enterica serovar Typhimurium vector expressing colonization factor antigen I (CFA/I) from enterotoxigenic Escherichia coli. In NK1R(-/-) mice, mucosal and serum IgA anti-CFA/I fimbrial responses were augmented, while secreted IgG anti-CFA/I fimbrial responses remained unaffected compared to those of BALB/c (NK1R(+/+)) mice. Supportive antibody-forming cells were present in the small intestinal lamina propria and spleen. To gain insight as to why the augmented S-IgA responses occurred, minimally, the responses were not attributed to differences in vaccine colonization of Peyer's patch (PP) and spleen or in their respective tissue weights. However, these S-IgA responses were supported by increased numbers of PP CD4(+) T helper (Th) cells secreting interleukin-5 (IL-5) and IL-6 and splenic CD4(+) Th cells secreting IL-6 compared to NK1R(+/+) mice. Challenge of naive NK1R(-/-) mice with wild-type Salmonella showed improved median survival compared to naive NK1R(+/+) mice. Data from peritoneal macrophage infection studies suggest that this survival is in part contributed by increased IL-10 production. Oral vaccination with Salmonella CFA/I or Salmonella vector showed no significant differences in conferred protection against wild-type challenge for either NK1R(-/-) or NK1R(+/+) mice. Thus, these studies suggest that SP mediation contributes to proinflammatory responses to Salmonella infections.
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PMID:Enhanced immunoglobulin A response and protection against Salmonella enterica serovar typhimurium in the absence of the substance P receptor. 1561 68

Promising recent developments in the therapeutic value of neuropeptide antagonists have generated renewed importance in understanding the functional role of neuropeptides in nociception and inflammation. To explore this relationship we examined behavioral changes and primary afferent neuronal plasticity following deep tissue inflammation. One hour following craniofacial muscle inflammation ipsilateral as well as contralateral head withdrawal thresholds and ipsi- and contralateral hindpaw withdrawal thresholds were lowered and remained reduced for 28 days. Elevated levels of calcitonin gene-related peptide (CGRP) within the trigeminal ganglion temporally correlated with this mechanical allodynia. Inflammation also induced an increase in the number of CGRP and substance P (SP)-immunopositive trigeminal ganglion neurons innervating inflamed muscle but did not evoke a shift in the size distribution of peptidergic muscle afferent neurons. Trigeminal proprioceptive muscle afferent neurons situated within the brainstem in the mesencephalic trigeminal nucleus did not express CGRP or SP prior to or following inflammation. Intravenous administration of CGRP receptor antagonist (8-37) two minutes prior to adjuvant injection blocked plasma extravasation and abolished both head and hindlimb mechanical allodynia. Local injection of CGRP antagonist directly into the masseter muscle prior to CFA produced similar, but less pronounced, effects. These findings indicate that unilateral craniofacial muscle inflammation produces mechanical allodynia at distant sites and upregulates CGRP and SP in primary afferent neurons innervating deep tissues. These data further implicate CGRP and SP in deep tissue nociceptive mechanisms and suggest that peptide antagonists may have therapeutic potential for musculoskeletal pain.
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PMID:Deep tissue inflammation upregulates neuropeptides and evokes nociceptive behaviors which are modulated by a neuropeptide antagonist. 1635 92

Dynamics of soil organic carbon mineralization affected by long-term fertilizations and temperature in relation to different soil carbon fractions were investigated in paddy soils. Soil samples were collected from the plough layer of 3 long-term national experimental sites in Xinhua, Ningxiang and Taojiang counties of Hunan Province. Mineralization of soil organic C was estimated by 33-day aerobic incubation at different temperatures of 10, 20 and 30 degrees C. The results showed that the rates of CO2 production were higher during the earlier phase (0-13 d) in all treatments, and then decreased according to a logarithm function. Higher incubation temperature strengthened C mineralization in the different treatments. The quantities of cumulative CO2 production in NPK with manure or straw treatments were greater than in inorganic fertilizers treatments. The Q10 values in the different soil treatments ranged from 1.01-1.53. There were significantly positive correlations between the Q10 values and soil total organic carbon (TOC), easy oxidation organic carbon (EOOC), humic acid carbon (C(HA)), fulvic acid carbon (CFA). The cumulative amount of mineralized C was significantly positively correlated with microbial biomass carbon (MBC) at 10 and 20 degrees C, but not significantly at 30 degrees C. Significant correlations were found between the cumulative amount of mineralized C and different soil carbon fractions and C(HA)/C(FA). The correlations of differ- ent soil carbon fractions with the ratio of cumulative mineralized C to TOC were negatively correlated at 10 degrees C, but not significantly at 20 and 30 degrees C. These results suggested that the application of NPK with manure or straw would be helpful to increase the sequestration of C in paddy soils and reduce its contribution of CO2 release in the atmosphere.
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PMID:[Characteristics of soil organic carbon mineralization at different temperatures in paddy soils under long-term fertilization]. 2512 34

Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia. BOLD signals from functional MRI showed that NPFFR2-Tg mice exhibited increased activation of pain-related brain regions after painful stimulation when compared to WT mice. Inflammatory mediators within the spinal cord, calcitonin gene-related peptide (CGRP) and substance P (SP), were up-regulated in NPFFR2-Tg and chronic NPFFR2 agonist-treated mice. In DRG cultures, treatment with an NPFFR2 agonist induced the expression and release of CGRP, an action which was blocked by NPFFR2 siRNA. Furthermore, treatment with a CGRP antagonist ameliorated the pain hyperalgesia in NPFFR2-Tg mice, returning the pain threshold to a control level. However, treatment with a SP antagonist reduced the pain responses in both WT and NPFFR2-Tg mice and did not suppress pain hypersensitivity in NPFFR2-Tg mice. Together, these results demonstrate that NPFFR2 activation modulates pain transmission by up-regulating the pain mediator CGRP, leading to hyperalgesia.
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PMID:Activation of NPFFR2 leads to hyperalgesia through the spinal inflammatory mediator CGRP in mice. 2817 53


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