Substance P - Knowledge

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1S/C63H98N18O13S/c1-37(2)33-45(57(89)74-41(53(68)85)27-32-95-3)73-52(84)36-72-54(86)46(34-38-15-6-4-7-16-38)78-58(90)47(35-39-17-8-5-9-18-39)79-56(88)42(23-25-50(66)82)75-55(87)43(24-26-51(67)83)76-59(91)49-22-14-31-81(49)62(94)44(20-10-11-28-64)77-60(92)48-21-13-30-80(48)61(93)40(65)19-12-29-71-63(69)70/h4-9,15-18,37,40-49H,10-14,19-36,64-65H2,1-3H3,(H2,66,82)(H2,67,83)(H2,68,85)(H,72,86)(H,73,84)(H,74,89)(H,75,87)(H,76,91)(H,77,92)(H,78,90)(H,79,88)(H4,69,70,71)/t40-,41-,42-,43-,44-,45-,46-,47-,48-,49-/m0/s1

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component has been identified or strongly suspected, and for which current treatments are absent or in need of improvement, abrogation of the SP-NK1 system continues to receive focus as a treatment strategy. Currently, the only completely developed method available in that regard is antagonism (blockade, inhibition) of the SP preferring receptor, i.e., by drugs known as neurokinin type 1 antagonists (also termed: SP antagonists, or tachykinin antagonists.) One such drug is

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1/C63H98N18O13S/c1-37(2)33-45(57(89)74-41(53(68)85)27-32-95-3)73-52(84)36-72-54(86)46(34-38-15-6-4-7-16-38)78-58(90)47(35-39-17-8-5-9-18-39)79-56(88)42(23-25-50(66)82)75-55(87)43(24-26-51(67)83)76-59(91)49-22-14-31-81(49)62(94)44(20-10-11-28-64)77-60(92)48-21-13-30-80(48)61(914,19-36,64-65H2,1-3H3,(H2,66,82)(H2,67,83)(H2,68,85)(H,72,86)(H,73,84)(H,74,89)(H,75,87)(H,76,91)(H,77,92)(H,78,90)(H,79,88)(H4,69,70,71)/t40-,41-,42-,43-,44-,45-,46-,47-,48-,49-/m0/s1

772:-like processes)) may not naturally subside in diseases marked by chronic inflammation (including cancer). The SP or its NK1R, as well as similar neuropeptides, appear to be vital targets capable of satisfying many unmet medical needs. The failure of clinical proof of concept studies, designed to confirm various preclinical predictions of efficacy, is currently a source of frustration and confusion among biomedical researchers. 190: 31: 1088:

central nervous system. However, given that NK1Rs are unprotected by a blood brain barrier in the area postrema just adjacent to neuronal structures in the medulla, and the activity of sendide (the peptide based NK1RA) against cisplatin-induced emesis in the ferret, it is likely that some peripheral exposure contributes to antiemetic effects, even if through vagal terminals in the clinical setting.

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as in cancer. When assayed in the human, the observed variability of the SP concentrations are large, and in some cases the assay methodology is questionable. SP concentrations cannot yet be used to diagnose disease clinically or gauge disease severity. It is not yet known whether changes in concentration of SP or density of its receptors is the cause of any given disease, or an effect.

479: 756:) is a neuropeptide – but only nominally so, as it is ubiquitous. Its receptor – the neurokinin type 1 – is distributed over cytoplasmic membranes of many cell types (neurons, glia, endothelia of capillaries and lymphatics, fibroblasts, stem cells, white blood cells) in many tissues and organs. SP amplifies or excites most cellular processes. 971:

to prevent the nausea and vomiting that accompanies chemotherapy, typically for cancer. With the exception of chemotherapy-induced nausea and vomiting, the patho-physiological basis of many of the disease groups listed below, for which NK1RAs have been studied as a therapeutic intervention, are to

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Elevation of serum, plasma, or tissue SP and/or its receptor (NK1R) has been associated with many diseases: sickle cell crisis; inflammatory bowel disease; major depression and related disorders; fibromyalgia; rheumatological; and infections such as HIV/AIDS and respiratory syncytial virus, as well

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and flare reaction. It has been shown that vasodilation to substance P is dependent on the NK1 receptor located on the endothelium. In contrast to other neuropeptides studied in human skin, substance P-induced vasodilation has been found to decline during continuous infusion. This possibly suggests

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Tachykinin / Substance P plays an evolutionarily conserved role in inducing aggressive behaviors. In rodents and cats, activation of hypothalamic neurons which release Substance P induces aggressive behaviors (defensive biting and predatory attack). Similarly, in fruit flies, tachykinin-releasing

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Substance P is a key first responder to most noxious/extreme stimuli (stressors), i.e., those with a potential to compromise an organism's biological integrity. SP is thus regarded as an immediate defense, stress, repair, survival system. The molecule, which is rapidly inactivated (or at times

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receptor signaling. NK1Rs are stimulated. In turn, a fairly complex reflex is triggered involving cranial nerves responsible for respiration, retroperistalsis, and general autonomic discharge. The actions of aprepitant are said to be entirely central, thus requiring passage of the drug into the

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in humans. SP and its induced cytokines promote multiplication of cells required for repair or replacement, growth of new blood vessels, and "leg-like pods" on cells (including cancer cells) bestowing upon them mobility, and metastasis. It has been suggested that cancer exploits the SP-NK1R to

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As increasingly documented, the SP-NK1R system induces or modulates many aspects of the immune response, including WBC production and activation, and cytokine expression, Reciprocally, cytokines may induce expression of SP and its NK1R. In this sense, for diseases in which a pro-inflammatory

850:, which is a local inflammatory response to certain types of infection or injury. Unfortunately, the reasons why NK1 receptor antagonists have failed as efficacious analgesics in well-conducted clinical proof of concept studies have not yet been persuasively elucidated. 845:

in primary afferents that respond to painful stimulation. Substance P and other sensory neuropeptides can be released from the peripheral terminals of sensory nerve fibers in the skin, muscle, and joints. It is proposed that this release is involved in

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Derocq JM, Ségui M, Blazy C, Emonds-Alt X, Le Fur G, Brelire JC, et al. (Dec 1996). "Effect of substance P on cytokine production by human astrocytic cells and blood mononuclear cells: characterization of novel tachykinin receptor antagonists".

3119:"Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease" 938:

The above processes are part and parcel to tissue integrity and repair. Substance P has been known to stimulate cell growth in normal and cancer cell line cultures, and it was shown that substance P could promote wound healing of non-healing

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When the innervation to substance P nerve terminals is lost, post-synaptic cells compensate for the loss of adequate neurotransmitter by increasing the expression of post-synaptic receptors. This, ultimately, leads to a condition known as

2003:"Absence of the SP/SP receptor circuitry in the substance P-precursor knockout mice or SP receptor, neurokinin (NK)1 knockout mice leads to an inhibited cytokine response in granulomas associated with murine Taenia crassiceps infection" 3046:

Berger M, Neth O, Ilmer M, Garnier A, Salinas-Martín MV, de Agustín Asencio JC, et al. (May 2014). "Hepatoblastoma cells express truncated neurokinin-1 receptor and can be growth inhibited by aprepitant in vitro and in vivo".

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further activated by peptidases) is rapidly released – repetitively and chronically, as warranted, in the presence of a stressor. Unique among biological processes, SP release (and expression of its NK1 Receptor (through

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Gerard NP, Garraway LA, Eddy RL, Shows TB, Iijima H, Paquet JL, et al. (Nov 1991). "Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones".

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Despite strong preclinical rationale, efforts to demonstrate efficacy of SP antagonists in inflammatory disease have been unproductive. A study in women with IBS confirmed that an NK1RAs antagonist was anxiolytic.

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Preclinical data support the notion that Substance P is an important element in pain perception. The sensory function of substance P is thought to be related to the transmission of pain information into the

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Geracioti TD, Carpenter LL, Owens MJ, Baker DG, Ekhator NN, Horn PS, et al. (Apr 2006). "Elevated cerebrospinal fluid substance p concentrations in posttraumatic stress disorder and major depression".

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Baloyannis S, Costa V, Deretzi G, Michmizos D. 1999. Intraventricular Administration of Substance P Increases the Dendritic Arborisation and the Synaptic Surfaces of Purkinje Cells in Rat's Cerebellum.

890:. In 2014, it was found that substance P played a role in male fruit fly aggression. Recently, it has been shown that substance P may play a critical role in long-term potentiation of aversive stimuli. 813:). Also, most of the cytokines, in turn, induce SP and the NK1 receptor. SP is particularly excitatory to cell growth and multiplication, via usual, as well as oncogenic drivers. SP is a trigger for 4387:

Halasz J, Zelena D, Toth M, Tulogdi A, Mikics E, Haller J (June 2009). "Substance P neurotransmission and violent aggression: the role of tachykinin NK(1) receptors in the hypothalamic attack area".

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neurons have been implicated in aggressive behaviors (lunging). In this context, male-specific tachykinin neurons control lunging behaviors that can be modulated by the amount of tachykinin release.

5958: 821:. Substance P and other sensory neuropeptides can be released from the peripheral terminals of sensory nerve fibers in the skin, muscle, and joints. It is proposed that this release is involved in 3331:

Vaerøy H, Helle R, Førre O, Kåss E, Terenius L (Jan 1988). "Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis".

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Michaels LA, Ohene-Frempong K, Zhao H, Douglas SD (Nov 1998). "Serum levels of substance P are elevated in patients with sickle cell disease and increase further during vaso-occlusive crisis".

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Stark D, van Hal S, Marriott D, Ellis J, Harkness J (Jan 2007). "Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis".

635:. Its tissue distribution and biologic actions were further investigated over the following decades. The eleven-amino-acid structure of the peptide was determined by Chang, et. al in 1971. 1839:

Bossaller C, Reither K, Hehlert-Friedrich C, Auch-Schwelk W, Graf K, Gräfe M, et al. (Oct 1992). "In vivo measurement of endothelium-dependent vasodilation with substance P in man".

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De Felipe C, Herrero JF, O'Brien JA, Palmer JA, Doyle CA, Smith AJ, et al. (Mar 1998). "Altered nociception, analgesia and aggression in mice lacking the receptor for substance P".

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King KA, Hu C, Rodriguez MM, Romaguera R, Jiang X, Piedimonte G (Feb 2001). "Exaggerated neurogenic inflammation and substance P receptor upregulation in RSV-infected weanling rats".

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Seckl MJ, Higgins T, Widmer F, Rozengurt E (Jan 1997). "substance P: a novel potent inhibitor of signal transduction and growth in vitro and in vivo in small cell lung cancer cells".

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Kovács KA, Steinmann M, Magistretti PJ, Halfon O, Cardinaux JR (Sep 2006). "C/EBPbeta couples dopamine signalling to substance P precursor gene expression in striatal neurones".

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Huskey SE, Dean BJ, Bakhtiar R, Sanchez RI, Tattersall FD, Rycroft W, et al. (Jun 2003). "Brain penetration of aprepitant, a substance P receptor antagonist, in ferrets".

4162:"Neurokinin-1-receptor antagonism decreases anxiety and emotional arousal circuit response to noxious visceral distension in women with irritable bowel syndrome: a pilot study" 2471:

Huston JP, Hasenöhrl RU, Boix F, Gerhardt P, Schwarting RK (1993). "Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine activity".

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Wong M, Jeng AY (Jan 1994). "Posttranslational modification of glycine-extended substance P by an alpha-amidating enzyme in cultured sensory neurons of dorsal root ganglia".

676:. Other neurokinin subtypes and neurokinin receptors that interact with SP have been reported as well. Amino acid residues that are responsible for the binding of SP and its 6190: 5951: 2241:"Inhibitor of apoptosis proteins (IAPs) and their antagonists regulate spontaneous and tumor necrosis factor (TNF)-induced proinflammatory cytokine and chemokine production" 930:. Their activation stimulates the vomiting reflex. Different emetic pathways exist, and substance P/NK1R appears to be within the final common pathway to regulate vomiting. 1631:, Cassano T, Radja F, Morgese MG, Cuomo V, Santarelli L, et al. (Apr 2007). "Neurokinin 1 receptor antagonism requires norepinephrine to increase serotonin function". 1195: 707:(5-HT) and neurons containing norepinephrine that are targeted by the currently used antidepressant drugs. The SP receptor promoter contains regions that are sensitive to 1752:

Pinto FM, Almeida TA, Hernandez M, Devillier P, Advenier C, Candenas ML (Jun 2004). "mRNA expression of tachykinins and tachykinin receptors in different human tissues".

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and related viruses appear to upregulate SP receptors, and rat studies suggest that NK1RAs may be useful in treating or limiting long term sequelae from such infections.

735:, it has been proposed that cytokines and neurotropic factors can induce NK-1. Also, SP can induce the cytokines that are capable of inducing NK-1 transcription factors. 3772:Łazarczyk M, Matyja E, Lipkowski A (2007). "Substance P and its receptors -- a potential target for novel medicines in malignant brain tumour therapies (mini-review)". 2159:"Metalloproteinases and transforming growth factor-alpha mediate substance P-induced mitogen-activated protein kinase activation and proliferation in human colonocytes" 1059:

In line with its role as a first line defense system, SP is released when toxicants or poisons come into contact with a range of receptors on cellular elements in the

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Brown SM, Lamberts DW, Reid TW, Nishida T, Murphy CJ (Jul 1997). "Neurotrophic and anhidrotic keratopathy treated with substance P and insulinlike growth factor 1".

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The role of SP in HIV-AIDS has been well-documented. Doses of aprepitant greater than those tested to date are required for demonstration of full efficacy.

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McGowan K, Kane A, Asarkof N, Wicks J, Guerina V, Kellum J, et al. (Aug 1983). "Entamoeba histolytica causes intestinal secretion: role of serotonin".

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Piedimonte G (Mar 2001). "Neural mechanisms of respiratory syncytial virus-induced inflammation and prevention of respiratory syncytial virus sequelae".

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Anichini M, Cesaretti S, Lepori M, Maddali Bongi S, Maresca M, Zoppi M (Jan 1997). "Substance P in the serum of patients with rheumatoid arthritis".

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Azzolina A, Bongiovanni A, Lampiasi N (Dec 2003). "Substance P induces TNF-alpha and IL-6 production through NF kappa B in peritoneal mast cells".

66: 6668: 3633:"Substance P enhances cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression on cultured rheumatoid fibroblast-like synoviocytes" 1915:

Rameshwar P, Gascon P, Ganea D (Mar 1992). "Immunoregulatory effects of neuropeptides. Stimulation of interleukin-2 production by substance p".

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Katsouni E, Sakkas P, Zarros A, Skandali N, Liapi C (August 2009). "The involvement of substance P in the induction of aggressive behavior".

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Substance P and the NK1-receptor are widely distributed in the brain and are found in brain regions that are specific to regulating emotion (

6806: 5920: 5915: 5677: 5571: 5451: 3479:"Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis" 2735:

Reid TW, Murphy CJ, Iwahashi CK, Foster BA, Mannis MJ (Aug 1993). "Stimulation of epithelial cell growth by the neuropeptide substance P".

7610: 7471: 6866: 6765: 6718: 6648: 5737: 5727: 5722: 5717: 5702: 5697: 5657: 2200:"The neuropeptide substance P activates p38 mitogen-activated protein kinase resulting in IL-6 expression independently from NF-kappa B" 7715: 5885: 5772: 5662: 5652: 5647: 3853:"Pathophysiology of nocturnal scratching in childhood atopic dermatitis: the role of brain-derived neurotrophic factor and substance P" 3852: 7730: 5752: 5707: 5642: 6708: 5787: 5682: 1050: 680:

are present in the extracellular loops and transmembrane regions of NK-1. Binding of SP to NK-1R results in internalization by the

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Palma C, Manzini S (Jan 1998). "Substance P induces secretion of immunomodulatory cytokines by human astrocytoma cells".

90: 487: 2849:"Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner" 4344:

Siegel A, Schubert KL, Shaikh MB (November 1997). "Neurotransmitters regulating defensive rage behavior in the cat".

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Hesketh PJ (Jul 2001). "Potential role of the NK1 receptor antagonists in chemotherapy-induced nausea and vomiting".

1265: 387: 4839: 4799: 1418:"Immunohistochemical localization of bombesin/gastrin-releasing peptide and substance P in primary sensory neurons" 78: 801:

properties, administered through the non-adrenergic, non-cholinergic nervous system (branch of the vagal system).

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Rupniak NM (May 2002). "New insights into the antidepressant actions of substance P (NK1 receptor) antagonists".

7675: 7096: 7091: 6541: 4646: 910:, contains high concentrations of substance P and its receptor, in addition to other neurotransmitters such as 708: 2516:"Substance P is a promoter of adult neural progenitor cell proliferation under normal and ischemic conditions" 1106:

as the post-synaptic nerves will become hypersensitive to any release of substance P into the synaptic cleft.

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Asahina K, Watanabe K, Duistermars BJ, Hoopfer E, González CR, Eyjólfsdóttir EA, et al. (January 2014).

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varying extents hypothesized to be initiated or advanced by a chronic non-homeostatic inflammatory response.

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where the complex disassociates. Subsequently, SP is degraded and NK-1R is re-expressed on the cell surface.

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Muñoz M, Rosso M, Coveñas R (2010). "A new frontier in the treatment of cancer: NK-1 receptor antagonists".

7784: 7061: 6622: 5456: 4732: 1868:"Neurokinin-1 receptor desensitization to consecutive microdialysis infusions of substance P in human skin" 1103: 728: 364: 291: 331: 83: 5070: 3003:

Muñoz M, Coveñas R (Oct 2013). "Involvement of substance P and the NK-1 receptor in cancer progression".

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Rameshwar P (Nov 1997). "Substance P: a regulatory neuropeptide for hematopoiesis and immune functions".

997: 839: 712: 253: 7818: 5029: 4113:"Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease" 3538:"Measurement of plasma-derived substance P: biological, methodological, and statistical considerations" 3442:

Palma C, Maggi CA (2000). "The role of tachykinins via NK1 receptors in progression of human gliomas".

1060: 673: 5476: 4600: 1538:"Delineation of the endocytic pathway of substance P and its seven-transmembrane domain NK1 receptor" 3631:

Lambert N, Lescoulié PL, Yassine-Diab B, Enault G, Mazières B, De Préval C, et al. (Aug 1998).

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Fehder WP, Sachs J, Uvaydova M, Douglas SD (1997). "Substance P as an immune modulator of anxiety".

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progress and metastasize, and that NK1RAs may be useful in the treatment of several cancer types.

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release. Substance P is involved in the axon reflex-mediated vasodilation to local heating and

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Muñoz M, Rosso M, Coveñas R (Jun 2011). "The NK-1 receptor: a new target in cancer therapy".

1234: 1004: 665: 611:. It is found in the brain and spinal cord and is associated with inflammatory processes and 3949: 3117:

Mantyh CR, Gates TS, Zimmerman RP, Welton ML, Passaro EP, Vigna SR, et al. (May 1988).

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Ebner K, Singewald N (Oct 2006). "The role of substance P in stress and anxiety responses".

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Campbell DE, Raftery N, Tustin R, Tustin NB, Desilvio ML, Cnaan A, et al. (Nov 2006).

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Zubrzycka M, Janecka A (Dec 2000). "Substance P: transmitter of nociception (Minireview)".

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Kearney CJ, Sheridan C, Cullen SP, Tynan GA, Logue SE, Afonina IS, et al. (Feb 2013).

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Ho WZ, Douglas SD (Dec 2004). "Substance P and neurokinin-1 receptor modulation of HIV".

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Yip J, Chahl LA (Apr 2001). "Localization of NK1 and NK3 receptors in guinea-pig brain".

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Katsanos GS, Anogeianaki A, Orso C, Tete S, Salini V, Antinolfi PL, et al. (2008).

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Donkin JJ, Turner RJ, Hassan I, Vink R (2007). "Substance P in traumatic brain injury".

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that infects the lower gastrointestinal tract of humans. The symptoms of infection are

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Belilos A, Gray C, Sanders C, Black D, Mays E, Richie C, et al. (December 2023).

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McGowan K, Guerina V, Wicks J, Donowitz M (1985). "Chapter 8: Secretory Hormones of

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Douglas SD, Ho WZ, Gettes DR, Cnaan A, Zhao H, Leserman J, et al. (Oct 2001).

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Singh D, Joshi DD, Hameed M, Qian J, Gascón P, Maloof PB, et al. (Jan 2000).

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O'Connor TM, O'Connell J, O'Brien DI, Goode T, Bredin CP, Shanahan F (Nov 2004).

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Chang MM, Leeman SE, Niall HD (July 1971). "Amino-acid sequence of substance P".

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group at the C-terminus. Substance P is released from the terminals of specific

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Proceedings of the National Academy of Sciences of the United States of America

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Proceedings of the National Academy of Sciences of the United States of America

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Proceedings of the National Academy of Sciences of the United States of America

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SP initiates expression of almost all known immunological chemical messengers (

628: 608: 543: 470: 4089: 2441: 7802: 7740: 7720: 7315: 7030: 6861: 6841: 6571: 6459: 6270: 6143: 6060: 5692: 5687: 5188: 5183: 5150: 4917: 4882: 4834: 4794: 4632: 4527: 4311: 3914: 3095: 1838: 1211: 1084: 1064: 907: 879: 871: 624: 587: 584: 519: 284: 4054: 2257: 1275: 7620: 7436: 7396: 7329: 7319: 7310: 7305: 7248: 7206: 6796: 6581: 6490: 6403: 6215: 6210: 6113: 5900: 5895: 5880: 5831: 5667: 5627: 5516: 5392: 5387: 5382: 5377: 5344: 5339: 5090: 4829: 4814: 4809: 4582: 4492: 4443: 4408: 4330: 4279: 4230: 4195: 4146: 4111:

Steinhoff MS, von Mentzer B, Geppetti P, Pothoulakis C, Bunnett NW (2014).

4019: 3957: 3922: 3879: 3785: 3758: 3701: 3609: 3571: 3522: 3463: 3428: 3317: 3282: 3233: 3143: 3068: 3024: 2989: 2927: 2892: 2833: 2721: 2686: 2620: 2572:

Bonham AC (Sep 1995). "Neurotransmitters in the CNS control of breathing".

2541: 2449: 2363: 2311: 2276: 2225: 2184: 2175: 2158: 2076: 2036: 1901: 1817: 1773: 1730: 1695: 1652: 1606: 1394: 1367: 1219: 1180: 1017: 875: 785: 692: 639: 547: 531: 5055: 4365: 4097: 4062: 3666: 3503: 3387: 3352: 3197: 3162: 3103: 2954: 2799: 2756: 2748: 2593: 2492: 2406: 2303: 2131: 2095: 1979: 1936: 1852: 1738: 1571: 1536:

Grady EF, Garland AM, Gamp PD, Lovett M, Payan DG, Bunnett NW (May 1995).

1522: 1487: 1451: 1402: 1310: 1302: 933: 7660: 7588: 7572: 7440: 7412: 7295: 7239: 7182: 7168: 6856: 6851: 6791: 6505: 6500: 6454: 6393: 6320: 6300: 6279: 6240: 6103: 6068: 5936: 5802: 5797: 5782: 5521: 5431: 5359: 5270: 5255: 5175: 5145: 5130: 5039: 4950: 4912: 4867: 4824: 4819: 4717: 4691: 4270: 4253: 4222: 3984: 3553: 1789: 1029: 887: 781: 646: 551: 119: 1553: 1479: 7650: 7541: 7456: 7446: 7402: 7386: 7382: 7273: 7139: 7007: 6990: 6888: 6734: 6662: 6658: 6605: 6551: 6510: 6335: 6325: 6310: 6178: 6088: 5910: 5856: 5851: 5807: 5767: 5762: 5747: 5742: 5732: 5672: 5637: 5632: 5622: 5323: 5287: 5277: 5260: 5226: 5198: 5155: 4988: 4902: 4740: 4676: 4110: 3802:

Substance P and the Neurokinin 1 receptor: From behavior to bioanalysis

2700:

Hornby PJ (Dec 2001). "Central neurocircuitry associated with emesis".

2639:, The New York Times, February 4, 2014, page D5 of the New York edition 2484: 1054: 968: 658: 596: 535: 527: 458: 304: 264: 114: 7044: 6902: 6473: 5536: 4467:"Neuromodulation and Strategic Action Choice in Drosophila Aggression" 3189: 2052:"Cytokine regulation of substance P expression in sympathetic neurons" 2018: 1808: 1791: 789: 7765: 7750: 7745: 7695: 7690: 7335: 7254: 7212: 7202: 6439: 6304: 5925: 5905: 5846: 5841: 5712: 5461: 5446: 5292: 5282: 5265: 5122: 5024: 4993: 4983: 4877: 4804: 4784: 4776: 4748: 4699: 4686: 2651:"Nucleus accumbens local circuit for cue-dependent aversive learning" 1076: 1025: 1009: 984:

and substance P have been found associated with increased itching in

923: 915: 842: 732: 704: 581: 578: 5981: 3373: 3309: 642:(previously known as substance K or neuromedin L) was isolated from 562:

gene. The deduced amino acid sequence of substance P is as follows:

469:

Except where otherwise noted, data are given for materials in their

7700: 7685: 7654: 7644: 7634: 7624: 7605: 7593: 7562: 7557: 7521: 7432: 7285: 7224: 7196: 7186: 7164: 6846: 6831: 6755: 6693: 6678: 6638: 6444: 6419: 6372: 6363: 6290: 6256: 6200: 6195: 6157: 6153: 6127: 6117: 6107: 6097: 6083: 6041: 5436: 5415: 5410: 5354: 4681: 2514:

Park SW, Yan YP, Satriotomo I, Vemuganti R, Dempsey RJ (Sep 2007).

1072: 1013: 919: 899: 878:, synaptic growth and dendritic arborisation, respiratory rhythm, 810: 696: 685: 681: 566: 3630: 2398: 2198:

Fiebich BL, Schleicher S, Butcher RD, Craig A, Lieb K (Nov 2000).

7735: 7600: 7566: 7535: 7499: 7357: 7339: 7259: 7216: 7156: 7124: 6934: 6835: 6786: 6759: 6751: 6698: 6632: 6448: 6424: 6345: 6294: 6183: 6046: 5481: 5466: 5086: 4753: 4546: 3249:"The role of substance P in depression: therapeutic implications" 3081: 2376: 911: 863: 643: 593: 590: 575: 569: 523: 340: 4601:"Neurochemical Substance P is Key to Understanding Pain Process" 1673: 1415: 1334:"An unidentified depressor substance in certain tissue extracts" 95: 7527: 7503: 7461: 7361: 7289: 7128: 7110: 6968: 6929: 6924: 6702: 6688: 6433: 6349: 6244: 6235: 6225: 6204: 6167: 6138: 6133: 6072: 6064: 6050: 6027: 5402: 1080: 985: 927: 818: 814: 572: 244: 102: 2340:. Progress in Brain Research. Vol. 161. pp. 97–109. 1751: 189: 30: 7531: 7267: 7263: 7220: 7134: 6903: 6770: 6747: 6387: 6264: 6147: 6078: 5315: 3682:

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

2561:

https://www.tandfonline.com/doi/abs/10.3109/00207450008986495

2197: 1063:, located in the floor of the fourth ventricle of the brain ( 991: 720: 716: 604: 224: 4421: 3210: 1416:

Panula P, Hadjiconstantinou M, Yang HY, Costa E (Oct 1983).

1193: 1161:

The International Journal of Biochemistry & Cell Biology

1035: 976:

Dermatological disorders: eczema/psoriasis, chronic pruritus

962:

Blockade for diseases with a chronic immunological component

7466: 7300: 7045: 6991: 6952: 6643: 6606: 6474: 4655: 4292: 4075: 3679: 3535: 2940: 2812: 2470: 1501:

Maggi CA (Sep 1995). "The mammalian tachykinin receptors".

1044: 981: 883: 612: 3938:

American Journal of Respiratory and Critical Care Medicine

3903:

American Journal of Respiratory Cell and Molecular Biology

3175: 3116: 2513: 2238: 2108: 623:

The original discovery of Substance P (SP) was in 1931 by

5541: 4293:

Nässel DR, Zandawala M, Kawada T, Satake H (2019-11-20).

4208: 3997: 797:(NK1). As is typical with many vasodilators, it also has 4850:

congenital insensitivity to pain with partial anhidrosis

3900: 3771: 2777: 2734: 1627: 649:

and was also found to stimulate intestinal contraction.

7351: 4624: 4386: 4032: 2847:

Meshki J, Douglas SD, Hu M, Leeman SE, Tuluc F (2011).

2822:

Journal of Biological Regulators and Homeostatic Agents

2648: 1464: 934:

Cell growth, proliferation, angiogenesis, and migration

858:

Substance P has been associated with the regulation of

631:

as a tissue extract that caused intestinal contraction

4251: 3045: 2338:

Neurotrauma: New Insights into Pathology and Treatment

2335: 2000: 1535: 4348:. The neurobiology of defensive behavior in animals. 3851:

Hon KL, Lam MC, Wong KY, Leung TF, Ng PC (Nov 2007).

2846: 5968: 4343: 4084:. Ciba Found. Symp. Vol. 112. pp. 139–54. 3476: 3400: 3330: 1914: 1196:"Substance P: structure, function, and therapeutics" 1194:Datar P, Srivastava S, Coutinho E, Govil G (2004). 784:. Substance P-induced vasodilation is dependent on 313: 5586: 1159:Harrison S, Geppetti P (Jun 2001). "Substance p". 3403:"Elevated substance P levels in HIV-infected men" 2967: 2905: 1865: 1792:"The role of substance P in inflammatory disease" 1247: 727:. Because these regions are related to complexed 7800: 4845:congenital insensitivity to pain with anhidrosis 4621:, Science Take, New York Times, February 3, 2014 4516:"To Study Aggression, a Fight Club for Flies-US" 4160:Tillisch K, Labus J, Nam B, et al. (2012). 4159: 3246: 2606: 1380: 1158: 1067:). Presumably, SP is released in or around the 352: 16:Chemical compound (polypeptide neurotransmitter) 4252:Diemunsch P, Joshi GP, Brichant JF (Jul 2009). 3850: 3298:Canadian Journal of Physiology and Pharmacology 2331: 2329: 2152: 1096: 212: 5532:Pituitary adenylate cyclase-activating peptide 2427: 2049: 1154: 1152: 5952: 5572: 5452:Cocaine- and amphetamine-regulated transcript 5071: 4640: 3714: 3583: 3581: 2001:Garza A, Weinstock J, Robinson P (Dec 2008). 1785: 1783: 1331: 1260:. San Francisco: Pearson, Benjamin Cummings. 1253: 3991: 3844: 3798: 3470: 3435: 3394: 3289: 3002: 2815:"Impact of substance P on cellular immunity" 2806: 2693: 2600: 2507: 2421: 2326: 2283: 1957: 1859: 1667: 1621: 1578: 952: 703:). They are found in close association with 5085: 3367: 3169: 3110: 3075: 2771: 2728: 2636:To Study Aggression, a Fight Club for Flies 2627: 2565: 2464: 2370: 1866:Wong BJ, Tublitz NJ, Minson CT (Nov 2005). 1832: 1710: 1529: 1494: 1325: 1187: 1149: 5966: 5959: 5945: 5579: 5565: 5078: 5064: 4647: 4633: 3935: 3721:Annals of the New York Academy of Sciences 3578: 3441: 1780: 1458: 1409: 1282: 1222:. Archived from the original on 2009-08-17 992:Infections: HIV-AIDS, measles, RSV, others 853: 294: 272: 4598: 4572: 4482: 4320: 4310: 4269: 4185: 4136: 3748: 3656: 3587: 3561: 3512: 3502: 3418: 3272: 3152: 3142: 2882: 2872: 2676: 2666: 2531: 2266: 2256: 2215: 2174: 2085: 2075: 2026: 1891: 1807: 1716: 1561: 1441: 1357: 1036:Inflammatory bowel disease (IBD)/cystitis 372: 3970: 1584: 1288: 1132:"Undecapeptide Definition & Meaning" 1051:Chemotherapy-induced nausea and vomiting 1045:Chemotherapy induced nausea and vomiting 947: 668:(NK1-receptor, NK1R). It belongs to the 4464: 4082:Microbial Toxins and Diarrhoeal Disease 3950:10.1164/ajrccm.163.supplement_1.2011113 3295: 2289: 1719:Clinical Immunology and Immunopathology 330: 7801: 4513: 4346:Neuroscience and Biobehavioral Reviews 4000:International Journal for Parasitology 2699: 2571: 1024:. This protozoan was found to secrete 684:-dependent mechanism to the acidified 546:. Substance P and the closely related 538:family of neuropeptides. It acts as a 285: 6139:CS gas (2-chlorobenzal malononitrile) 5940: 5560: 5059: 4628: 2557:International Journal of Neuroscience 1500: 1200:Current Topics in Medicinal Chemistry 402:Key: ADNPLDHMAVUMIW-CUZNLEPHSA-N 252: 232: 3637:Clinical and Experimental Immunology 3247:Schwarz MJ, Ackenheil M (Mar 2002). 2792:10.1001/archopht.1997.01100160096021 7711:N-(p-Amylcinnamoyl)anthranilic acid 6827:N-(p-Amylcinnamoyl)anthranilic acid 6567:N-(p-Amylcinnamoyl)anthranilic acid 4484:10.1146/annurev-neuro-072116-031240 4080:". In D. Evered, J. Whelan (eds.). 2245:The Journal of Biological Chemistry 2163:The Journal of Biological Chemistry 1332:V Euler US, Gaddum JH (June 1931). 415:Key: ADNPLDHMAVUMIW-CUZNLEPHBU 343: 13: 3860:The British Journal of Dermatology 3827:"'Blood chemicals link' to eczema" 3805:(Ph.D.). University of Groningen. 3715:Douglas SD, Leeman SE (Jan 2011). 3253:Dialogues in Clinical Neuroscience 3214:The American Journal of Psychiatry 2050:Freidin M, Kessler JA (Apr 1991). 1434:10.1523/JNEUROSCI.03-10-02021.1983 14: 7830: 4592: 1091: 4840:Congenital insensitivity to pain 4800:Paroxysmal extreme pain disorder 4389:European Journal of Pharmacology 4178:10.1111/j.1365-2036.2011.04958.x 3872:10.1111/j.1365-2133.2007.08149.x 3741:10.1111/j.1749-6632.2010.05826.x 3649:10.1046/j.1365-2249.1998.00621.x 3420:10.1097/00002030-200110190-00019 2737:Journal of Cellular Biochemistry 2702:The American Journal of Medicine 1754:European Journal of Pharmacology 1688:10.1111/j.1471-4159.2006.03957.x 1633:European Neuropsychopharmacology 1291:Journal of Neuroscience Research 838:. Substance P coexists with the 477: 188: 29: 5442:Calcitonin gene-related peptide 4540: 4507: 4458: 4415: 4380: 4337: 4286: 4245: 4211:Drug Metabolism and Disposition 4202: 4153: 4104: 4069: 4026: 3964: 3929: 3894: 3792: 3765: 3708: 3673: 3624: 3542:Clinical and Vaccine Immunology 3529: 3324: 3265:10.31887/DCNS.2002.4.1/mschwarz 3240: 3204: 3039: 2996: 2961: 2934: 2899: 2840: 2642: 2548: 2232: 2191: 2146: 2102: 2043: 1994: 1951: 1908: 1745: 1645:10.1016/j.euroneuro.2006.07.004 804: 775: 473:(at 25 °C , 100 kPa). 4436:10.1016/j.peptides.2009.05.001 4258:British Journal of Anaesthesia 3602:10.1016/j.jneuroim.2004.08.022 3017:10.1016/j.peptides.2013.07.024 1796:Journal of Cellular Physiology 1374: 1350:10.1113/jphysiol.1931.sp002763 1254:Reece JB, Campbell NA (2005). 1124: 748:Substance P ("P" standing for 1: 7785:Receptor/signaling modulators 6134:CR gas (dibenzoxazepine; DBO) 4471:Annual Review of Neuroscience 4358:10.1016/S0149-7634(96)00056-5 3456:10.1016/s0024-3205(00)00692-5 2714:10.1016/S0002-9343(01)00849-X 2346:10.1016/S0079-6123(06)61007-8 2124:10.1016/s0014-5793(96)01346-4 1972:10.1016/s0165-5728(97)00167-7 1599:10.1016/S0167-0115(00)00228-7 1542:Molecular Biology of the Cell 1173:10.1016/S1357-2725(01)00031-0 1118: 1109: 1069:nucleus of the solitary tract 5457:Delta-sleep-inducing peptide 4401:10.1016/j.ejphar.2009.03.050 4012:10.1016/j.ijpara.2006.09.009 3694:10.1016/j.bbamcr.2003.09.003 3345:10.1016/0304-3959(88)90019-X 2874:10.1371/journal.pone.0025332 2668:10.1016/j.celrep.2023.113488 2586:10.1016/0034-5687(95)00045-F 2217:10.4049/jimmunol.165.10.5606 2157:, Pothoulakis C (Oct 2004). 1929:10.1016/0165-5728(92)90156-f 1884:10.1113/jphysiol.2005.095372 1766:10.1016/j.ejphar.2004.05.016 1515:10.1016/0306-3623(94)00292-U 1104:denervation supersensitivity 1097:Denervation supersensitivity 1071:upon integrated activity of 1008:is a unicellular parasitic 729:signal transduction pathways 618: 7: 7809:Genes on human chromosome 7 7413:Paracetamol (acetaminophen) 6321:Paracetamol (acetaminophen) 6191:Farnesyl thiosalicylic acid 6019:15-Deoxy-Δ-prostaglandin J2 3971:Steinitz H (Aug 1979). "". 2970:Current Medicinal Chemistry 2007:The Journal of Parasitology 1422:The Journal of Neuroscience 1028:as well as substance P and 893: 840:excitatory neurotransmitter 743: 738: 652: 463:1347.63 g/mol 10: 7835: 4619:Fight Club for Flies video 4565:10.1016/j.cell.2013.11.045 4129:10.1152/physrev.00031.2013 3590:Journal of Neuroimmunology 3226:10.1176/appi.ajp.163.4.637 3061:10.1016/j.jhep.2013.12.024 2982:10.2174/092986710790416308 2920:10.2174/138945011795528796 1960:Journal of Neuroimmunology 1917:Journal of Neuroimmunology 1061:chemoreceptor trigger zone 1048: 550:(NKA) are produced from a 526:composed of a chain of 11 7778: 7581: 7054: 7043: 7023: 7000: 6989: 6961: 6912: 6901: 6779: 6615: 6604: 6529: 6483: 6472: 6412: 5991: 5980: 5865: 5816: 5597: 5477:Gastrin-releasing peptide 5424: 5401: 5370: 5314: 5305: 5248: 5225: 5197: 5174: 5121: 5112: 5097: 5007: 4974: 4941: 4895: 4860: 4775: 4731: 4708: 4669: 4662: 4299:Frontiers in Neuroscience 4090:10.1002/9780470720936.ch8 2780:Archives of Ophthalmology 2708:(8 Suppl 8A): 106S–112S. 2442:10.1007/s00726-006-0335-9 2292:Supportive Care in Cancer 1872:The Journal of Physiology 1676:Journal of Neurochemistry 1338:The Journal of Physiology 1239:: CS1 maint: unfit URL ( 953:Quantification in disease 467: 424: 383: 196: 187: 166: 156: 151: 147: 130: 125: 113: 101: 89: 77: 65: 57: 49: 44: 28: 23: 6398:Umbellularia californica 4654: 4599:Russell J (2001-09-14). 4312:10.3389/fnins.2019.01262 4166:Aliment. Pharmacol. Ther 3915:10.1165/ajrcmb.24.2.4264 3799:van der Hart MG (2009). 3096:10.1182/blood.V92.9.3148 1212:10.2174/1568026043451636 780:Substance P is a potent 530:residues) and a type of 7368:N-Arachidonoyl dopamine 7150:Andrographis paniculata 4961:Posteromarginal nucleus 4896:Measurement and testing 4514:Gorman J (2014-02-03). 4465:Asahina K (July 2017). 4055:10.1126/science.6308760 2520:Journal of Neurosurgery 2258:10.1074/jbc.M112.422410 2153:Koon HW, Zhao D, Na X, 854:Mood, anxiety, learning 848:neurogenic inflammation 828: 823:neurogenic inflammation 725:epidermal growth factor 24:tachykinin, precursor 1 7789:Ion channel modulators 7518:Tetrahydrocannabivarin 7013:Tripterygium wilfordii 6379:Tetrahydrocannabiorcol 5527:Pancreatic polypeptide 3833:. BBC News. 2007-08-26 3774:Folia Neuropathologica 3144:10.1073/pnas.85.9.3235 2574:Respiration Physiology 2533:10.3171/JNS-07/09/0593 2176:10.1074/jbc.M408523200 2077:10.1073/pnas.88.8.3200 1731:10.1006/clin.1997.4446 1395:10.1038/newbio232086a0 836:central nervous system 793:an internalization of 7346:Lysophosphatidic acid 5758:Nolpitantium besilate 5045:Drug-seeking behavior 4933:Visual analogue scale 4078:Entamoeba histolytica 3504:10.1073/pnas.97.1.388 3178:Neuroimmunomodulation 3049:Journal of Hepatology 2749:10.1002/jcb.240520411 2609:Endocrine Regulations 2304:10.1007/s005200000199 2204:Journal of Immunology 1303:10.1002/jnr.490370113 1049:Further information: 1005:Entamoeba histolytica 998:Respiratory syncytial 948:Clinical significance 666:neurokinin 1 receptor 7726:Pregnenolone sulfate 7547:Euphorbia resinifera 7489:Euphorbia resinifera 7418:Phenylacetylrinvanil 7378:N-Oleoylethanolamide 7326:Homodihydrocapsaicin 6714:Pregnenolone sulfate 6577:Pregnenolone sulfate 6384:Thiopropanal S-oxide 6369:Tetrahydrocannabinol 6057:Allyl isothiocyanate 5472:Galanin-like peptide 4956:Anterolateral system 4605:Fibromyalgia Library 4223:10.1124/dmd.31.6.785 3554:10.1128/CVI.00174-06 2908:Current Drug Targets 1503:General Pharmacology 1257:Biology, 7th Edition 556:alternative splicing 7631:Cannabigerolic acid 7393:Nordihydrocapsaicin 7354:(acidic conditions) 5588:Neurokinin receptor 4047:1983Sci...221..762M 3733:2011NYASA1217...83D 3495:2000PNAS...97..388S 3376:Revue du Rhumatisme 3135:1988PNAS...85.3235M 2865:2011PLoSO...625332M 2559:, 101(1-4):89-107. 2391:1998Natur.392..394D 2068:1991PNAS...88.3200F 1587:Regulatory Peptides 1554:10.1091/mbc.6.5.509 1480:10.1021/bi00108a006 799:bronchoconstrictive 701:periaqueductal gray 670:tachykinin receptor 664:for substance P is 534:, belonging to the 184: 7594:Vernonia tweediana 7173:African blue basil 7145:Bisandrographolide 6731:Steviol glycosides 6684:Hydroxycitronellal 6430:Dehydroligustilide 6250:Angelica acutiloba 6164:Dehydroligustilide 5035:Philosophy of pain 4710:Respiratory system 4520:The New York Times 4271:10.1093/bja/aep125 3973:Leber, Magen, Darm 3944:(3 Pt 2): S18-21. 2485:10.1007/BF02244906 2473:Psychopharmacology 560:preprotachykinin A 500:Infobox references 182: 7819:Neurotransmitters 7796: 7795: 7774: 7773: 7706:Meclofenamic acid 7512:melegueta peppers 7383:Nonivamide (PAVA) 7119:melegueta peppers 7039: 7038: 6985: 6984: 6897: 6896: 6817:Meclofenamic acid 6740:Stevia rebaudiana 6600: 6599: 6562:Meclofenamic acid 6468: 6467: 6358:melegueta peppers 6331:Phenacyl chloride 6286:N-Methylmaleimide 6276:Methyl salicylate 6221:Hydrogen peroxide 6174:Diallyl disulfide 6036:melegueta peppers 5934: 5933: 5554: 5553: 5550: 5549: 5301: 5300: 5053: 5052: 4908:Cold pressor test 4891: 4890: 3812:978-90-367-3874-3 3190:10.1159/000097314 2019:10.1645/GE-1481.1 1878:(Pt 3): 1047–56. 1809:10.1002/jcp.20061 926:, and endogenous 508:Chemical compound 506: 505: 180: 179: 176: 175: 7826: 7641:Cannabigerovarin 7373:N-Oleoyldopamine 7279:Euodia ruticarpa 7245:Dihydrocapsaicin 7052: 7051: 7048: 6998: 6997: 6994: 6910: 6909: 6906: 6654:Cooling Agent 10 6613: 6612: 6609: 6481: 6480: 6477: 5999:4-Hydroxynonenal 5989: 5988: 5985: 5970: 5961: 5954: 5947: 5938: 5937: 5581: 5574: 5567: 5558: 5557: 5312: 5311: 5119: 5118: 5080: 5073: 5066: 5057: 5056: 5008:Related concepts 4999:Pain eradication 4757: 4744: 4695: 4667: 4666: 4663:By region/system 4649: 4642: 4635: 4626: 4625: 4615: 4613: 4612: 4587: 4586: 4576: 4559:(1–2): 221–235. 4544: 4538: 4537: 4535: 4534: 4511: 4505: 4504: 4486: 4462: 4456: 4455: 4430:(8): 1586–1591. 4419: 4413: 4412: 4384: 4378: 4377: 4341: 4335: 4334: 4324: 4314: 4290: 4284: 4283: 4273: 4249: 4243: 4242: 4206: 4200: 4199: 4189: 4157: 4151: 4150: 4140: 4108: 4102: 4101: 4073: 4067: 4066: 4030: 4024: 4023: 3995: 3989: 3988: 3968: 3962: 3961: 3933: 3927: 3926: 3898: 3892: 3891: 3857: 3848: 3842: 3841: 3839: 3838: 3823: 3817: 3816: 3796: 3790: 3789: 3769: 3763: 3762: 3752: 3712: 3706: 3705: 3677: 3671: 3670: 3660: 3628: 3622: 3621: 3585: 3576: 3575: 3565: 3548:(11): 1197–203. 3533: 3527: 3526: 3516: 3506: 3474: 3468: 3467: 3439: 3433: 3432: 3422: 3398: 3392: 3391: 3371: 3365: 3364: 3328: 3322: 3321: 3293: 3287: 3286: 3276: 3244: 3238: 3237: 3208: 3202: 3201: 3173: 3167: 3166: 3156: 3146: 3114: 3108: 3107: 3079: 3073: 3072: 3043: 3037: 3036: 3000: 2994: 2993: 2965: 2959: 2958: 2938: 2932: 2931: 2903: 2897: 2896: 2886: 2876: 2844: 2838: 2837: 2819: 2810: 2804: 2803: 2775: 2769: 2768: 2732: 2726: 2725: 2697: 2691: 2690: 2680: 2670: 2646: 2640: 2631: 2625: 2624: 2604: 2598: 2597: 2569: 2563: 2552: 2546: 2545: 2535: 2511: 2505: 2504: 2468: 2462: 2461: 2425: 2419: 2418: 2374: 2368: 2367: 2333: 2324: 2323: 2287: 2281: 2280: 2270: 2260: 2236: 2230: 2229: 2219: 2195: 2189: 2188: 2178: 2169:(44): 45519–27. 2150: 2144: 2143: 2106: 2100: 2099: 2089: 2079: 2047: 2041: 2040: 2030: 1998: 1992: 1991: 1955: 1949: 1948: 1912: 1906: 1905: 1895: 1863: 1857: 1856: 1836: 1830: 1829: 1811: 1787: 1778: 1777: 1749: 1743: 1742: 1714: 1708: 1707: 1671: 1665: 1664: 1625: 1619: 1618: 1582: 1576: 1575: 1565: 1533: 1527: 1526: 1498: 1492: 1491: 1462: 1456: 1455: 1445: 1413: 1407: 1406: 1378: 1372: 1371: 1361: 1329: 1323: 1322: 1286: 1280: 1279: 1251: 1245: 1244: 1238: 1230: 1228: 1227: 1191: 1185: 1184: 1156: 1147: 1146: 1144: 1142: 1128: 554:precursor after 540:neurotransmitter 490: 484: 481: 480: 432:Chemical formula 376: 356: 345: 334: 317: 298: 287: 276: 256: 236: 216: 192: 185: 181: 149: 148: 33: 21: 20: 7834: 7833: 7829: 7828: 7827: 7825: 7824: 7823: 7799: 7798: 7797: 7792: 7770: 7761:Tolfenamic acid 7681:Flufenamic acid 7577: 7484:Resiniferatoxin 7477:Ruta graveolens 7240:Diacyl glycerol 7035: 7019: 6981: 6977: 6957: 6943: 6893: 6879:Tolfenamic acid 6872:Ruta graveolens 6812:Flufenamic acid 6775: 6724:Ruta graveolens 6635:(intracellular) 6596: 6592:Tolfenamic acid 6547:Flufenamic acid 6525: 6501:Diacyl glycerol 6464: 6408: 6094:Cannabichromene 6004:4-Oxo-2-nonenal 5976: 5965: 5935: 5930: 5870: 5861: 5821: 5812: 5602: 5593: 5585: 5555: 5546: 5502:Neuropeptide VF 5497:Neuropeptide SF 5492:Neuropeptide FF 5487:Neuropeptide AF 5420: 5397: 5366: 5307: 5297: 5244: 5221: 5193: 5170: 5139: 5114:Opioid peptides 5108: 5093: 5084: 5054: 5049: 5003: 4970: 4943:Pathophysiology 4937: 4928:Tail flick test 4887: 4856: 4771: 4755: 4742: 4733:Musculoskeletal 4727: 4704: 4693: 4658: 4653: 4610: 4608: 4607:. ProHealth.com 4595: 4590: 4545: 4541: 4532: 4530: 4512: 4508: 4463: 4459: 4420: 4416: 4385: 4381: 4342: 4338: 4291: 4287: 4250: 4246: 4207: 4203: 4158: 4154: 4109: 4105: 4074: 4070: 4041:(4612): 762–4. 4031: 4027: 3996: 3992: 3969: 3965: 3934: 3930: 3899: 3895: 3855: 3849: 3845: 3836: 3834: 3825: 3824: 3820: 3813: 3797: 3793: 3770: 3766: 3713: 3709: 3678: 3674: 3629: 3625: 3586: 3579: 3534: 3530: 3475: 3471: 3450:(9): 985–1001. 3440: 3436: 3399: 3395: 3372: 3368: 3329: 3325: 3310:10.1139/y02-048 3294: 3290: 3245: 3241: 3209: 3205: 3174: 3170: 3115: 3111: 3080: 3076: 3044: 3040: 3001: 2997: 2966: 2962: 2943:Cancer Research 2939: 2935: 2904: 2900: 2845: 2841: 2817: 2811: 2807: 2776: 2772: 2733: 2729: 2698: 2694: 2647: 2643: 2633:Gorman, James, 2632: 2628: 2605: 2601: 2570: 2566: 2553: 2549: 2512: 2508: 2479:(2–3): 147–62. 2469: 2465: 2426: 2422: 2385:(6674): 394–7. 2375: 2371: 2356: 2334: 2327: 2288: 2284: 2237: 2233: 2210:(10): 5606–11. 2196: 2192: 2151: 2147: 2107: 2103: 2048: 2044: 1999: 1995: 1966:(1–2): 127–37. 1956: 1952: 1913: 1909: 1864: 1860: 1837: 1833: 1788: 1781: 1750: 1746: 1715: 1711: 1672: 1668: 1626: 1622: 1583: 1579: 1534: 1530: 1499: 1495: 1474:(44): 10640–6. 1463: 1459: 1414: 1410: 1379: 1375: 1330: 1326: 1287: 1283: 1268: 1252: 1248: 1232: 1231: 1225: 1223: 1192: 1188: 1157: 1150: 1140: 1138: 1136:Merriam-Webster 1130: 1129: 1125: 1121: 1112: 1099: 1094: 1057: 1047: 1038: 994: 980:High levels of 978: 964: 955: 950: 936: 896: 856: 831: 807: 778: 746: 741: 655: 621: 509: 502: 497: 496: 495: ?) 486: 482: 478: 474: 452: 448: 444: 440: 434: 420: 417: 416: 413: 412: 404: 403: 400: 399: 391: 390: 379: 359: 346: 320: 307: 279: 259: 239: 219: 206: 40: 17: 12: 11: 5: 7832: 7822: 7821: 7816: 7811: 7794: 7793: 7779: 7776: 7775: 7772: 7771: 7769: 7768: 7763: 7758: 7753: 7748: 7743: 7738: 7733: 7728: 7723: 7718: 7713: 7708: 7703: 7698: 7693: 7688: 7683: 7678: 7673: 7668: 7663: 7658: 7648: 7638: 7628: 7618: 7613: 7608: 7603: 7598: 7585: 7583: 7579: 7578: 7576: 7575: 7570: 7560: 7555: 7539: 7525: 7515: 7497: 7481: 7469: 7464: 7459: 7454: 7451:Dorrigo pepper 7444: 7430: 7423:Phorbol esters 7420: 7415: 7410: 7400: 7390: 7380: 7375: 7370: 7365: 7355: 7348: 7343: 7333: 7323: 7313: 7308: 7303: 7298: 7293: 7283: 7271: 7257: 7252: 7242: 7237: 7232: 7210: 7200: 7193:Cannabidivarin 7190: 7180: 7161:camphor laurel 7154: 7142: 7137: 7132: 7122: 7104: 7099: 7094: 7089: 7084: 7079: 7074: 7069: 7064: 7058: 7056: 7049: 7041: 7040: 7037: 7036: 7034: 7033: 7027: 7025: 7021: 7020: 7018: 7017: 7004: 7002: 6995: 6987: 6986: 6983: 6982: 6980: 6979: 6975: 6971: 6965: 6963: 6959: 6958: 6956: 6955: 6950: 6945: 6941: 6937: 6932: 6927: 6922: 6916: 6914: 6907: 6899: 6898: 6895: 6894: 6892: 6891: 6886: 6881: 6876: 6864: 6859: 6854: 6849: 6844: 6839: 6829: 6824: 6822:Mefenamic acid 6819: 6814: 6809: 6804: 6799: 6794: 6789: 6783: 6781: 6777: 6776: 6774: 6773: 6768: 6763: 6744: 6728: 6716: 6711: 6706: 6696: 6691: 6686: 6681: 6676: 6671: 6666: 6656: 6651: 6646: 6641: 6636: 6630: 6625: 6619: 6617: 6610: 6602: 6601: 6598: 6597: 6595: 6594: 6589: 6584: 6579: 6574: 6569: 6564: 6559: 6554: 6549: 6544: 6539: 6533: 6531: 6527: 6526: 6524: 6523: 6518: 6515:St John's wort 6508: 6503: 6498: 6495:St John's wort 6487: 6485: 6478: 6470: 6469: 6466: 6465: 6463: 6462: 6457: 6452: 6442: 6437: 6427: 6422: 6416: 6414: 6410: 6409: 6407: 6406: 6401: 6391: 6381: 6376: 6366: 6361: 6343: 6340:Dorrigo pepper 6333: 6328: 6323: 6318: 6308: 6298: 6288: 6283: 6273: 6268: 6261:Sichuan pepper 6254: 6238: 6233: 6231:Isothiocyanate 6228: 6223: 6218: 6213: 6208: 6198: 6193: 6188: 6176: 6171: 6161: 6151: 6141: 6136: 6131: 6124:Cinnamaldehyde 6121: 6111: 6101: 6091: 6086: 6081: 6076: 6054: 6044: 6039: 6021: 6016: 6011: 6006: 6001: 5995: 5993: 5986: 5978: 5977: 5964: 5963: 5956: 5949: 5941: 5932: 5931: 5929: 5928: 5923: 5918: 5913: 5908: 5903: 5898: 5889: 5888: 5883: 5874: 5872: 5868: 5863: 5862: 5860: 5859: 5854: 5849: 5844: 5835: 5834: 5825: 5823: 5819: 5814: 5813: 5811: 5810: 5805: 5800: 5795: 5790: 5785: 5780: 5775: 5770: 5765: 5760: 5755: 5750: 5745: 5740: 5735: 5730: 5725: 5720: 5715: 5710: 5705: 5700: 5695: 5690: 5685: 5680: 5675: 5670: 5665: 5660: 5655: 5650: 5645: 5640: 5635: 5630: 5625: 5616: 5615: 5606: 5604: 5600: 5595: 5594: 5584: 5583: 5576: 5569: 5561: 5552: 5551: 5548: 5547: 5545: 5544: 5539: 5534: 5529: 5524: 5519: 5514: 5512:Neuropeptide Y 5509: 5507:Neuropeptide S 5504: 5499: 5494: 5489: 5484: 5479: 5474: 5469: 5464: 5459: 5454: 5449: 5444: 5439: 5434: 5428: 5426: 5422: 5421: 5419: 5418: 5413: 5407: 5405: 5399: 5398: 5396: 5395: 5390: 5385: 5380: 5374: 5372: 5368: 5367: 5365: 5364: 5363: 5362: 5357: 5349: 5348: 5347: 5342: 5337: 5326: 5320: 5318: 5309: 5303: 5302: 5299: 5298: 5296: 5295: 5290: 5285: 5280: 5275: 5274: 5273: 5263: 5258: 5252: 5250: 5246: 5245: 5243: 5242: 5240:Leu-enkephalin 5237: 5235:Met-enkephalin 5231: 5229: 5223: 5222: 5220: 5219: 5214: 5209: 5203: 5201: 5195: 5194: 5192: 5191: 5186: 5180: 5178: 5172: 5171: 5169: 5168: 5166:β-Neoendorphin 5163: 5161:α-Neoendorphin 5158: 5153: 5148: 5143: 5142: 5141: 5137: 5127: 5125: 5116: 5110: 5109: 5101: 5099: 5095: 5094: 5083: 5082: 5075: 5068: 5060: 5051: 5050: 5048: 5047: 5042: 5037: 5032: 5027: 5022: 5020:Pain tolerance 5017: 5015:Pain threshold 5011: 5009: 5005: 5004: 5002: 5001: 4996: 4991: 4986: 4980: 4978: 4972: 4971: 4969: 4968: 4963: 4958: 4953: 4947: 4945: 4939: 4938: 4936: 4935: 4930: 4925: 4923:Hot plate test 4920: 4915: 4910: 4905: 4899: 4897: 4893: 4892: 4889: 4888: 4886: 4885: 4880: 4875: 4870: 4864: 4862: 4858: 4857: 4855: 4854: 4853: 4852: 4847: 4837: 4832: 4827: 4822: 4817: 4812: 4807: 4802: 4797: 4792: 4790:Pain asymbolia 4787: 4781: 4779: 4773: 4772: 4770: 4769: 4764: 4759: 4751: 4746: 4737: 4735: 4729: 4728: 4726: 4725: 4720: 4714: 4712: 4706: 4705: 4703: 4702: 4697: 4689: 4684: 4679: 4673: 4671: 4664: 4660: 4659: 4652: 4651: 4644: 4637: 4629: 4623: 4622: 4616: 4594: 4593:External links 4591: 4589: 4588: 4539: 4506: 4457: 4414: 4395:(1–3): 35–43. 4379: 4352:(6): 733–742. 4336: 4285: 4244: 4201: 4172:(3): 360–367. 4152: 4123:(1): 265–301. 4103: 4068: 4025: 3990: 3963: 3928: 3893: 3843: 3818: 3811: 3791: 3764: 3707: 3688:(1–3): 75–83. 3672: 3623: 3596:(1–2): 48–55. 3577: 3528: 3469: 3434: 3413:(15): 2043–5. 3393: 3366: 3323: 3288: 3239: 3203: 3168: 3109: 3090:(9): 3148–51. 3074: 3038: 2995: 2960: 2933: 2898: 2839: 2805: 2770: 2727: 2692: 2661:(12): 113488. 2641: 2626: 2615:(4): 195–201. 2599: 2564: 2547: 2506: 2463: 2420: 2369: 2354: 2325: 2282: 2251:(7): 4878–90. 2231: 2190: 2145: 2101: 2042: 1993: 1950: 1923:(1–2): 65–74. 1907: 1858: 1831: 1779: 1760:(2–3): 233–9. 1744: 1709: 1666: 1620: 1593:(1–2): 55–62. 1577: 1528: 1493: 1457: 1428:(10): 2021–9. 1408: 1373: 1324: 1281: 1266: 1246: 1186: 1148: 1122: 1120: 1117: 1111: 1108: 1098: 1095: 1093: 1092:Other findings 1090: 1046: 1043: 1037: 1034: 1022:abdominal pain 993: 990: 977: 974: 963: 960: 954: 951: 949: 946: 935: 932: 902:center in the 895: 892: 860:mood disorders 855: 852: 830: 827: 806: 803: 777: 774: 745: 742: 740: 737: 672:sub-family of 654: 651: 629:John H. Gaddum 620: 617: 609:sensory nerves 601: 600: 544:neuromodulator 507: 504: 503: 498: 476: 475: 471:standard state 468: 465: 464: 461: 455: 454: 450: 446: 442: 438: 435: 430: 427: 426: 422: 421: 419: 418: 414: 410: 408: 407: 405: 401: 397: 395: 394: 386: 385: 384: 381: 380: 378: 377: 369: 367: 361: 360: 358: 357: 349: 347: 339: 336: 335: 328: 322: 321: 319: 318: 310: 308: 303: 300: 299: 289: 281: 280: 278: 277: 269: 267: 261: 260: 258: 257: 249: 247: 241: 240: 238: 237: 229: 227: 221: 220: 218: 217: 209: 207: 202: 199: 198: 194: 193: 178: 177: 174: 173: 168: 164: 163: 158: 154: 153: 145: 144: 134: 128: 127: 123: 122: 117: 111: 110: 105: 99: 98: 93: 87: 86: 81: 75: 74: 69: 63: 62: 59: 55: 54: 51: 47: 46: 42: 41: 39:of substance P 34: 26: 25: 15: 9: 6: 4: 3: 2: 7831: 7820: 7817: 7815: 7814:Neuropeptides 7812: 7810: 7807: 7806: 7804: 7791: 7790: 7786: 7783: 7777: 7767: 7764: 7762: 7759: 7757: 7754: 7752: 7749: 7747: 7744: 7742: 7741:Ruthenium red 7739: 7737: 7734: 7732: 7729: 7727: 7724: 7722: 7721:Niflumic acid 7719: 7717: 7714: 7712: 7709: 7707: 7704: 7702: 7699: 7697: 7694: 7692: 7689: 7687: 7684: 7682: 7679: 7677: 7674: 7672: 7669: 7667: 7664: 7662: 7659: 7656: 7652: 7649: 7646: 7642: 7639: 7636: 7632: 7629: 7626: 7622: 7619: 7617: 7614: 7612: 7609: 7607: 7604: 7602: 7599: 7596: 7595: 7590: 7589:α-Spinasterol 7587: 7586: 7584: 7580: 7574: 7571: 7568: 7564: 7561: 7559: 7556: 7553: 7552: 7548: 7543: 7540: 7537: 7533: 7529: 7526: 7523: 7519: 7516: 7513: 7509: 7505: 7501: 7498: 7495: 7494: 7490: 7485: 7482: 7479: 7478: 7473: 7470: 7468: 7465: 7463: 7460: 7458: 7455: 7452: 7448: 7445: 7442: 7438: 7434: 7431: 7428: 7424: 7421: 7419: 7416: 7414: 7411: 7408: 7404: 7401: 7398: 7394: 7391: 7388: 7384: 7381: 7379: 7376: 7374: 7371: 7369: 7366: 7363: 7359: 7356: 7353: 7349: 7347: 7344: 7341: 7337: 7334: 7331: 7327: 7324: 7321: 7317: 7316:Homocapsaicin 7314: 7312: 7309: 7307: 7304: 7302: 7299: 7297: 7294: 7291: 7287: 7284: 7281: 7280: 7275: 7272: 7269: 7265: 7261: 7258: 7256: 7253: 7250: 7246: 7243: 7241: 7238: 7236: 7233: 7230: 7229:wild bergamot 7226: 7222: 7218: 7214: 7211: 7208: 7204: 7201: 7198: 7194: 7191: 7188: 7184: 7181: 7178: 7177:camphor basil 7174: 7170: 7166: 7162: 7158: 7155: 7152: 7151: 7146: 7143: 7141: 7138: 7136: 7133: 7130: 7126: 7123: 7120: 7116: 7112: 7108: 7105: 7103: 7100: 7098: 7095: 7093: 7090: 7088: 7085: 7083: 7080: 7078: 7075: 7073: 7070: 7068: 7065: 7063: 7060: 7059: 7057: 7053: 7050: 7047: 7042: 7032: 7031:Ruthenium red 7029: 7028: 7026: 7022: 7015: 7014: 7009: 7006: 7005: 7003: 6999: 6996: 6993: 6988: 6978: 6972: 6970: 6967: 6966: 6964: 6960: 6954: 6951: 6949: 6946: 6944: 6938: 6936: 6933: 6931: 6928: 6926: 6923: 6921: 6918: 6917: 6915: 6911: 6908: 6905: 6900: 6890: 6887: 6885: 6882: 6880: 6877: 6874: 6873: 6868: 6865: 6863: 6862:Ruthenium red 6860: 6858: 6855: 6853: 6850: 6848: 6845: 6843: 6842:Niflumic acid 6840: 6837: 6833: 6830: 6828: 6825: 6823: 6820: 6818: 6815: 6813: 6810: 6808: 6805: 6803: 6800: 6798: 6795: 6793: 6790: 6788: 6785: 6784: 6782: 6778: 6772: 6769: 6767: 6764: 6762:; indirectly) 6761: 6757: 6753: 6749: 6745: 6742: 6741: 6736: 6732: 6729: 6726: 6725: 6720: 6717: 6715: 6712: 6710: 6707: 6704: 6700: 6697: 6695: 6692: 6690: 6687: 6685: 6682: 6680: 6677: 6675: 6672: 6670: 6669:Frescolat MGA 6667: 6664: 6660: 6657: 6655: 6652: 6650: 6647: 6645: 6642: 6640: 6637: 6634: 6631: 6629: 6626: 6624: 6621: 6620: 6618: 6614: 6611: 6608: 6603: 6593: 6590: 6588: 6585: 6583: 6580: 6578: 6575: 6573: 6572:Niflumic acid 6570: 6568: 6565: 6563: 6560: 6558: 6555: 6553: 6550: 6548: 6545: 6543: 6540: 6538: 6535: 6534: 6532: 6528: 6522: 6519: 6516: 6512: 6509: 6507: 6504: 6502: 6499: 6496: 6492: 6489: 6488: 6486: 6482: 6479: 6476: 6471: 6461: 6460:Ruthenium red 6458: 6456: 6453: 6450: 6446: 6443: 6441: 6438: 6435: 6431: 6428: 6426: 6423: 6421: 6418: 6417: 6415: 6411: 6405: 6402: 6399: 6395: 6392: 6389: 6385: 6382: 6380: 6377: 6374: 6370: 6367: 6365: 6362: 6359: 6355: 6351: 6347: 6344: 6341: 6337: 6334: 6332: 6329: 6327: 6324: 6322: 6319: 6316: 6312: 6309: 6306: 6302: 6299: 6296: 6292: 6289: 6287: 6284: 6281: 6277: 6274: 6272: 6271:Methylglyoxal 6269: 6266: 6262: 6258: 6255: 6252: 6251: 6246: 6242: 6239: 6237: 6234: 6232: 6229: 6227: 6224: 6222: 6219: 6217: 6214: 6212: 6209: 6206: 6202: 6199: 6197: 6194: 6192: 6189: 6186: 6185: 6180: 6177: 6175: 6172: 6169: 6165: 6162: 6159: 6155: 6152: 6149: 6145: 6144:Cuminaldehyde 6142: 6140: 6137: 6135: 6132: 6129: 6125: 6122: 6119: 6115: 6112: 6109: 6105: 6102: 6099: 6095: 6092: 6090: 6087: 6085: 6082: 6080: 6077: 6074: 6070: 6066: 6062: 6058: 6055: 6052: 6048: 6045: 6043: 6040: 6037: 6033: 6029: 6025: 6022: 6020: 6017: 6015: 6012: 6010: 6007: 6005: 6002: 6000: 5997: 5996: 5994: 5990: 5987: 5984: 5979: 5975: 5972: 5962: 5957: 5955: 5950: 5948: 5943: 5942: 5939: 5927: 5924: 5922: 5919: 5917: 5914: 5912: 5909: 5907: 5904: 5902: 5899: 5897: 5894: 5891: 5890: 5887: 5884: 5882: 5879: 5876: 5875: 5873: 5871: 5864: 5858: 5855: 5853: 5850: 5848: 5845: 5843: 5840: 5837: 5836: 5833: 5830: 5827: 5826: 5824: 5822: 5815: 5809: 5806: 5804: 5801: 5799: 5796: 5794: 5791: 5789: 5786: 5784: 5781: 5779: 5776: 5774: 5771: 5769: 5766: 5764: 5761: 5759: 5756: 5754: 5751: 5749: 5746: 5744: 5741: 5739: 5736: 5734: 5731: 5729: 5726: 5724: 5721: 5719: 5716: 5714: 5711: 5709: 5706: 5704: 5701: 5699: 5696: 5694: 5693:Fosnetupitant 5691: 5689: 5688:Fosaprepitant 5686: 5684: 5681: 5679: 5676: 5674: 5671: 5669: 5666: 5664: 5661: 5659: 5656: 5654: 5651: 5649: 5646: 5644: 5641: 5639: 5636: 5634: 5631: 5629: 5626: 5624: 5621: 5618: 5617: 5614: 5611: 5608: 5607: 5605: 5603: 5596: 5592: 5589: 5582: 5577: 5575: 5570: 5568: 5563: 5562: 5559: 5543: 5540: 5538: 5535: 5533: 5530: 5528: 5525: 5523: 5520: 5518: 5515: 5513: 5510: 5508: 5505: 5503: 5500: 5498: 5495: 5493: 5490: 5488: 5485: 5483: 5480: 5478: 5475: 5473: 5470: 5468: 5465: 5463: 5460: 5458: 5455: 5453: 5450: 5448: 5445: 5443: 5440: 5438: 5435: 5433: 5430: 5429: 5427: 5423: 5417: 5414: 5412: 5409: 5408: 5406: 5404: 5400: 5394: 5391: 5389: 5386: 5384: 5381: 5379: 5376: 5375: 5373: 5369: 5361: 5358: 5356: 5353: 5352: 5350: 5346: 5343: 5341: 5338: 5336: 5333: 5332: 5330: 5327: 5325: 5322: 5321: 5319: 5317: 5313: 5310: 5308:neuropeptides 5304: 5294: 5291: 5289: 5286: 5284: 5281: 5279: 5276: 5272: 5269: 5268: 5267: 5264: 5262: 5259: 5257: 5254: 5253: 5251: 5247: 5241: 5238: 5236: 5233: 5232: 5230: 5228: 5224: 5218: 5215: 5213: 5210: 5208: 5205: 5204: 5202: 5200: 5196: 5190: 5189:Endomorphin-2 5187: 5185: 5184:Endomorphin-1 5182: 5181: 5179: 5177: 5173: 5167: 5164: 5162: 5159: 5157: 5154: 5152: 5151:Big dynorphin 5149: 5147: 5144: 5140: 5134: 5133: 5132: 5129: 5128: 5126: 5124: 5120: 5117: 5115: 5111: 5107: 5106: 5100: 5096: 5092: 5091:neuropeptides 5088: 5081: 5076: 5074: 5069: 5067: 5062: 5061: 5058: 5046: 5043: 5041: 5038: 5036: 5033: 5031: 5028: 5026: 5023: 5021: 5018: 5016: 5013: 5012: 5010: 5006: 5000: 4997: 4995: 4992: 4990: 4987: 4985: 4982: 4981: 4979: 4977: 4973: 4967: 4964: 4962: 4959: 4957: 4954: 4952: 4949: 4948: 4946: 4944: 4940: 4934: 4931: 4929: 4926: 4924: 4921: 4919: 4918:Grimace scale 4916: 4914: 4911: 4909: 4906: 4904: 4901: 4900: 4898: 4894: 4884: 4883:Low back pain 4881: 4879: 4876: 4874: 4871: 4869: 4866: 4865: 4863: 4859: 4851: 4848: 4846: 4843: 4842: 4841: 4838: 4836: 4835:Referred pain 4833: 4831: 4828: 4826: 4823: 4821: 4818: 4816: 4813: 4811: 4808: 4806: 4803: 4801: 4798: 4796: 4795:Pain disorder 4793: 4791: 4788: 4786: 4783: 4782: 4780: 4778: 4774: 4768: 4767:Delayed-onset 4765: 4763: 4760: 4758: 4752: 4750: 4747: 4745: 4739: 4738: 4736: 4734: 4730: 4724: 4721: 4719: 4716: 4715: 4713: 4711: 4707: 4701: 4698: 4696: 4690: 4688: 4685: 4683: 4680: 4678: 4675: 4674: 4672: 4670:Head and neck 4668: 4665: 4661: 4657: 4650: 4645: 4643: 4638: 4636: 4631: 4630: 4627: 4620: 4617: 4606: 4602: 4597: 4596: 4584: 4580: 4575: 4570: 4566: 4562: 4558: 4554: 4550: 4543: 4529: 4525: 4521: 4517: 4510: 4502: 4498: 4494: 4490: 4485: 4480: 4476: 4472: 4468: 4461: 4453: 4449: 4445: 4441: 4437: 4433: 4429: 4425: 4418: 4410: 4406: 4402: 4398: 4394: 4390: 4383: 4375: 4371: 4367: 4363: 4359: 4355: 4351: 4347: 4340: 4332: 4328: 4323: 4318: 4313: 4308: 4304: 4300: 4296: 4289: 4281: 4277: 4272: 4267: 4263: 4259: 4255: 4248: 4240: 4236: 4232: 4228: 4224: 4220: 4217:(6): 785–91. 4216: 4212: 4205: 4197: 4193: 4188: 4183: 4179: 4175: 4171: 4167: 4163: 4156: 4148: 4144: 4139: 4134: 4130: 4126: 4122: 4118: 4114: 4107: 4099: 4095: 4091: 4087: 4083: 4079: 4072: 4064: 4060: 4056: 4052: 4048: 4044: 4040: 4036: 4029: 4021: 4017: 4013: 4009: 4005: 4001: 3994: 3986: 3982: 3978: 3975:(in German). 3974: 3967: 3959: 3955: 3951: 3947: 3943: 3939: 3932: 3924: 3920: 3916: 3912: 3908: 3904: 3897: 3889: 3885: 3881: 3877: 3873: 3869: 3865: 3861: 3854: 3847: 3832: 3828: 3822: 3814: 3808: 3804: 3803: 3795: 3787: 3783: 3780:(3): 99–107. 3779: 3775: 3768: 3760: 3756: 3751: 3746: 3742: 3738: 3734: 3730: 3726: 3722: 3718: 3711: 3703: 3699: 3695: 3691: 3687: 3683: 3676: 3668: 3664: 3659: 3654: 3650: 3646: 3643:(2): 269–75. 3642: 3638: 3634: 3627: 3619: 3615: 3611: 3607: 3603: 3599: 3595: 3591: 3584: 3582: 3573: 3569: 3564: 3559: 3555: 3551: 3547: 3543: 3539: 3532: 3524: 3520: 3515: 3510: 3505: 3500: 3496: 3492: 3489:(1): 388–93. 3488: 3484: 3480: 3473: 3465: 3461: 3457: 3453: 3449: 3445: 3444:Life Sciences 3438: 3430: 3426: 3421: 3416: 3412: 3408: 3404: 3397: 3389: 3385: 3381: 3377: 3370: 3362: 3358: 3354: 3350: 3346: 3342: 3338: 3334: 3327: 3319: 3315: 3311: 3307: 3304:(5): 489–94. 3303: 3299: 3292: 3284: 3280: 3275: 3270: 3266: 3262: 3258: 3254: 3250: 3243: 3235: 3231: 3227: 3223: 3220:(4): 637–43. 3219: 3215: 3207: 3199: 3195: 3191: 3187: 3183: 3179: 3172: 3164: 3160: 3155: 3150: 3145: 3140: 3136: 3132: 3129:(9): 3235–9. 3128: 3124: 3120: 3113: 3105: 3101: 3097: 3093: 3089: 3085: 3078: 3070: 3066: 3062: 3058: 3055:(5): 985–94. 3054: 3050: 3042: 3034: 3030: 3026: 3022: 3018: 3014: 3010: 3006: 2999: 2991: 2987: 2983: 2979: 2976:(6): 504–16. 2975: 2971: 2964: 2956: 2952: 2948: 2944: 2937: 2929: 2925: 2921: 2917: 2914:(6): 909–21. 2913: 2909: 2902: 2894: 2890: 2885: 2880: 2875: 2870: 2866: 2862: 2859:(9): e25332. 2858: 2854: 2850: 2843: 2835: 2831: 2827: 2823: 2816: 2809: 2801: 2797: 2793: 2789: 2785: 2781: 2774: 2766: 2762: 2758: 2754: 2750: 2746: 2743:(4): 476–85. 2742: 2738: 2731: 2723: 2719: 2715: 2711: 2707: 2703: 2696: 2688: 2684: 2679: 2674: 2669: 2664: 2660: 2656: 2652: 2645: 2638: 2637: 2630: 2622: 2618: 2614: 2610: 2603: 2595: 2591: 2587: 2583: 2580:(3): 219–30. 2579: 2575: 2568: 2562: 2558: 2551: 2543: 2539: 2534: 2529: 2525: 2521: 2517: 2510: 2502: 2498: 2494: 2490: 2486: 2482: 2478: 2474: 2467: 2459: 2455: 2451: 2447: 2443: 2439: 2436:(3): 251–72. 2435: 2431: 2424: 2416: 2412: 2408: 2404: 2400: 2399:10.1038/32904 2396: 2392: 2388: 2384: 2380: 2373: 2365: 2361: 2357: 2355:9780444530172 2351: 2347: 2343: 2339: 2332: 2330: 2321: 2317: 2313: 2309: 2305: 2301: 2297: 2293: 2286: 2278: 2274: 2269: 2264: 2259: 2254: 2250: 2246: 2242: 2235: 2227: 2223: 2218: 2213: 2209: 2205: 2201: 2194: 2186: 2182: 2177: 2172: 2168: 2164: 2160: 2156: 2149: 2141: 2137: 2133: 2129: 2125: 2121: 2117: 2113: 2105: 2097: 2093: 2088: 2083: 2078: 2073: 2069: 2065: 2062:(8): 3200–3. 2061: 2057: 2053: 2046: 2038: 2034: 2029: 2024: 2020: 2016: 2013:(6): 1253–8. 2012: 2008: 2004: 1997: 1989: 1985: 1981: 1977: 1973: 1969: 1965: 1961: 1954: 1946: 1942: 1938: 1934: 1930: 1926: 1922: 1918: 1911: 1903: 1899: 1894: 1889: 1885: 1881: 1877: 1873: 1869: 1862: 1854: 1850: 1847:(5): 284–90. 1846: 1842: 1835: 1827: 1823: 1819: 1815: 1810: 1805: 1802:(2): 167–80. 1801: 1797: 1793: 1786: 1784: 1775: 1771: 1767: 1763: 1759: 1755: 1748: 1740: 1736: 1732: 1728: 1725:(2): 129–33. 1724: 1720: 1713: 1705: 1701: 1697: 1693: 1689: 1685: 1682:(5): 1390–9. 1681: 1677: 1670: 1662: 1658: 1654: 1650: 1646: 1642: 1639:(5): 328–38. 1638: 1634: 1630: 1624: 1616: 1612: 1608: 1604: 1600: 1596: 1592: 1588: 1581: 1573: 1569: 1564: 1559: 1555: 1551: 1548:(5): 509–24. 1547: 1543: 1539: 1532: 1524: 1520: 1516: 1512: 1509:(5): 911–44. 1508: 1504: 1497: 1489: 1485: 1481: 1477: 1473: 1469: 1461: 1453: 1449: 1444: 1439: 1435: 1431: 1427: 1423: 1419: 1412: 1404: 1400: 1396: 1392: 1389:(29): 86–87. 1388: 1384: 1377: 1369: 1365: 1360: 1355: 1351: 1347: 1343: 1339: 1335: 1328: 1320: 1316: 1312: 1308: 1304: 1300: 1297:(1): 97–102. 1296: 1292: 1285: 1277: 1273: 1269: 1267:9780805371468 1263: 1259: 1258: 1250: 1242: 1236: 1221: 1217: 1213: 1209: 1206:(1): 75–103. 1205: 1201: 1197: 1190: 1182: 1178: 1174: 1170: 1167:(6): 555–76. 1166: 1162: 1155: 1153: 1137: 1133: 1127: 1123: 1116: 1107: 1105: 1089: 1086: 1085:acetylcholine 1082: 1078: 1074: 1070: 1066: 1065:area postrema 1062: 1056: 1052: 1042: 1033: 1031: 1027: 1023: 1019: 1015: 1011: 1007: 1006: 1001: 999: 989: 987: 983: 973: 970: 959: 945: 942: 931: 929: 925: 921: 917: 913: 909: 908:area postrema 906:, called the 905: 901: 891: 889: 885: 881: 880:neurotoxicity 877: 873: 872:reinforcement 869: 865: 861: 851: 849: 844: 841: 837: 826: 824: 820: 816: 812: 802: 800: 796: 791: 787: 783: 773: 771: 767: 763: 757: 755: 751: 750:"Preparation" 736: 734: 730: 726: 722: 718: 714: 710: 706: 702: 698: 694: 689: 687: 683: 679: 675: 671: 667: 663: 660: 650: 648: 645: 641: 636: 634: 630: 626: 625:Ulf von Euler 616: 614: 610: 606: 599:(RPKPQQFFGLM) 598: 595: 592: 589: 586: 583: 580: 577: 574: 571: 568: 565: 564: 563: 561: 557: 553: 549: 545: 541: 537: 533: 529: 525: 521: 520:undecapeptide 517: 513: 501: 494: 489: 472: 466: 462: 460: 457: 456: 436: 433: 429: 428: 423: 406: 393: 392: 389: 382: 375: 371: 370: 368: 366: 363: 362: 355: 351: 350: 348: 342: 338: 337: 333: 329: 327: 324: 323: 316: 312: 311: 309: 306: 302: 301: 297: 293: 290: 288: 286:ECHA InfoCard 283: 282: 275: 271: 270: 268: 266: 263: 262: 255: 251: 250: 248: 246: 243: 242: 235: 231: 230: 228: 226: 223: 222: 215: 211: 210: 208: 205: 201: 200: 195: 191: 186: 172: 169: 165: 162: 159: 155: 150: 146: 143: 142: 138: 135: 133: 129: 124: 121: 118: 116: 112: 109: 106: 104: 100: 97: 94: 92: 88: 85: 82: 80: 76: 73: 70: 68: 64: 60: 56: 52: 48: 43: 38: 35:Spacefilling 32: 27: 22: 19: 7781: 7780: 7621:Cannabigerol 7592: 7545: 7487: 7475: 7437:black pepper 7397:chili pepper 7330:chili pepper 7320:chili pepper 7311:Hepoxilin B3 7306:Hepoxilin A3 7277: 7249:chili pepper 7207:chili pepper 7148: 7011: 6870: 6797:Clotrimazole 6738: 6722: 6674:Frescolat ML 6582:Progesterone 6520: 6491:Adhyperforin 6404:WIN 55,212-2 6397: 6248: 6216:Hepoxilin B3 6211:Hepoxilin A3 6182: 6114:Cannabigerol 5901:Fezolinetant 5896:Elinzanetant 5893:Antagonists: 5892: 5881:Neurokinin B 5877: 5839:Antagonists: 5838: 5832:Neurokinin A 5828: 5668:Elinzanetant 5628:Befetupitant 5620:Antagonists: 5619: 5612: 5609: 5517:Neurophysins 5345:Neurokinin B 5340:Neurokinin A 5334: 5176:Endomorphins 5102: 4965: 4830:Phantom pain 4815:Hyperalgesia 4810:Chronic pain 4694:(swallowing) 4692:Odynophagia 4609:. Retrieved 4604: 4556: 4552: 4542: 4531:. Retrieved 4519: 4509: 4477:(1): 51–75. 4474: 4470: 4460: 4427: 4423: 4417: 4392: 4388: 4382: 4349: 4345: 4339: 4302: 4298: 4288: 4261: 4257: 4247: 4214: 4210: 4204: 4169: 4165: 4155: 4120: 4117:Physiol. Rev 4116: 4106: 4081: 4077: 4071: 4038: 4034: 4028: 4006:(1): 11–20. 4003: 3999: 3993: 3979:(4): 175–9. 3976: 3972: 3966: 3941: 3937: 3931: 3909:(2): 101–7. 3906: 3902: 3896: 3866:(5): 922–5. 3863: 3859: 3846: 3835:. Retrieved 3830: 3821: 3801: 3794: 3777: 3773: 3767: 3727:(1): 83–95. 3724: 3720: 3710: 3685: 3681: 3675: 3640: 3636: 3626: 3593: 3589: 3545: 3541: 3531: 3486: 3482: 3472: 3447: 3443: 3437: 3410: 3406: 3396: 3382:(1): 18–21. 3379: 3375: 3369: 3336: 3332: 3326: 3301: 3297: 3291: 3256: 3252: 3242: 3217: 3213: 3206: 3181: 3177: 3171: 3126: 3122: 3112: 3087: 3083: 3077: 3052: 3048: 3041: 3008: 3004: 2998: 2973: 2969: 2963: 2946: 2942: 2936: 2911: 2907: 2901: 2856: 2852: 2842: 2825: 2821: 2808: 2786:(7): 926–7. 2783: 2779: 2773: 2740: 2736: 2730: 2705: 2701: 2695: 2658: 2655:Cell Reports 2654: 2644: 2634: 2629: 2612: 2608: 2602: 2577: 2573: 2567: 2556: 2550: 2526:(3): 593–9. 2523: 2519: 2509: 2476: 2472: 2466: 2433: 2429: 2423: 2382: 2378: 2372: 2337: 2298:(5): 350–4. 2295: 2291: 2285: 2248: 2244: 2234: 2207: 2203: 2193: 2166: 2162: 2148: 2118:(3): 321–5. 2115: 2112:FEBS Letters 2111: 2104: 2059: 2055: 2045: 2010: 2006: 1996: 1963: 1959: 1953: 1920: 1916: 1910: 1875: 1871: 1861: 1844: 1840: 1834: 1799: 1795: 1757: 1753: 1747: 1722: 1718: 1712: 1679: 1675: 1669: 1636: 1632: 1623: 1590: 1586: 1580: 1545: 1541: 1531: 1506: 1502: 1496: 1471: 1468:Biochemistry 1467: 1460: 1425: 1421: 1411: 1386: 1382: 1376: 1344:(1): 74–87. 1341: 1337: 1327: 1294: 1290: 1284: 1256: 1249: 1235:cite journal 1224:. Retrieved 1203: 1199: 1189: 1164: 1160: 1139:. Retrieved 1126: 1113: 1100: 1058: 1039: 1018:constipation 1003: 1002: 995: 979: 965: 956: 937: 897: 876:neurogenesis 857: 832: 808: 805:Inflammation 795:neurokinin-1 786:nitric oxide 779: 776:Vasodilation 758: 753: 749: 747: 731:mediated by 693:hypothalamus 690: 656: 640:Neurokinin A 637: 632: 622: 602: 548:neurokinin A 532:neuropeptide 515: 511: 510: 254:ChEMBL235363 197:Identifiers 183:Substance P 139: 58:Alt. symbols 18: 7756:Tivanisiran 7661:Capsazepine 7573:Zucapsaicin 7441:long pepper 7407:Pacific yew 7296:GSK1016790A 7183:Cannabidiol 7169:camphorweed 6857:RQ-00203078 6852:PF-05105679 6792:Capsazepine 6557:GSK2293017A 6521:Substance P 6506:GSK1702934A 6455:PF-04745637 6394:Umbellulone 6315:Pacific yew 6301:Oleocanthal 6280:wintergreen 6241:Ligustilide 6104:Cannabidiol 6069:horseradish 5803:Vestipitant 5798:Tradipitant 5793:Telmapitant 5783:Serlopitant 5778:SDZ NKT 343 5613:Substance P 5522:Neurotensin 5432:Angiotensin 5371:Neuromedins 5360:Physalaemin 5335:Substance P 5329:Tachykinins 5324:Bradykinins 5271:Hemorphin-4 5256:Adrenorphin 5227:Enkephalins 5217:γ-Endorphin 5212:β-Endorphin 5207:α-Endorphin 5146:Dynorphin B 5136:Dynorphin A 5131:Dynorphin A 5040:Cancer pain 4966:Substance P 4951:Nociception 4913:Dolorimeter 4868:Pelvic pain 4825:Hyperpathia 4820:Hypoalgesia 4741:Arthralgia 4723:Pleurodynia 4718:Sore throat 4264:(1): 7–13. 3339:(1): 21–6. 3259:(1): 21–9. 3184:(1): 42–8. 2949:(1): 51–4. 2828:(2): 93–8. 2430:Amino Acids 1141:17 November 1030:neurotensin 888:nociception 782:vasodilator 678:antagonists 647:spinal cord 552:polyprotein 512:Substance P 425:Properties 332:Substance+P 292:100.046.845 234:CHEBI:80308 161:Swiss-model 45:Identifiers 7803:Categories 7651:Cannabinol 7551:pooissonii 7542:Tinyatoxin 7493:pooissonii 7457:Probenecid 7447:Polygodial 7403:Paclitaxel 7387:PAVA spray 7274:Evodiamine 7225:pepperwort 7140:Anandamide 7107:α-Sanshool 7055:Activators 7008:Triptolide 7001:Activators 6913:Activators 6889:TRPM4-IN-5 6807:Elismetrep 6735:stevioside 6663:eucalyptus 6659:Eucalyptol 6623:ADP-ribose 6616:Activators 6552:GSK417651A 6511:Hyperforin 6484:Activators 6364:Tear gases 6336:Polygodial 6326:PF-4840154 6311:Paclitaxel 6179:Dicentrine 6089:Bradykinin 6024:α-Sanshool 5992:Activators 5974:modulators 5921:SB-222,200 5916:SB-218,795 5911:Pavinetant 5857:Saredutant 5852:Nepadutant 5808:Vofopitant 5768:Rolapitant 5763:Orvepitant 5748:Netupitant 5743:Maropitant 5733:Lanepitant 5678:Figopitant 5673:Ezlopitant 5638:Casopitant 5633:Burapitant 5623:Aprepitant 5591:modulators 5351:amphibian 5288:Spinorphin 5278:Nociceptin 5261:Amidorphin 5199:Endorphins 5156:Leumorphin 5123:Dynorphins 4989:Anesthesia 4976:Management 4903:Pain scale 4873:Proctalgia 4777:Neurologic 4677:Eye strain 4611:2008-11-01 4533:2022-03-24 3837:2008-11-01 1226:2008-11-01 1119:References 1110:Aggression 1055:Aprepitant 969:aprepitant 699:, and the 659:endogenous 536:tachykinin 528:amino acid 459:Molar mass 374:675VGV5J1D 305:IUPHAR/BPS 265:ChemSpider 214:33507-63-0 204:CAS Number 157:Structures 152:Search for 126:Other data 61:TAC2, NKNA 7782:See also: 7766:TRPV3-74a 7751:SB-705498 7746:SB-366791 7696:Lanthanum 7691:HC-067047 7611:Asivatrep 7472:Rutamarin 7336:Incensole 7286:Gingerols 7255:Estradiol 7231:, others) 7213:Carvacrol 7203:Capsaicin 7097:13-oxoODE 7087:12S-HpETE 7067:5',6'-EET 6867:Rutamarin 6766:Thio-BCTC 6719:Rutamarin 6649:Coolact P 6440:HC-030031 6305:olive oil 6201:Gingerols 6014:12S-HpETE 5926:Talnetant 5906:Osanetant 5878:Agonists: 5847:Ibodutant 5842:GR-159897 5829:Agonists: 5738:LY-306740 5728:L-758,298 5723:L-743,310 5718:L-741,671 5713:L-733,060 5703:GW-597599 5698:GR-203040 5658:CP-122721 5610:Agonists: 5462:FMRFamide 5447:Carnosine 5331:: mammal 5293:Valorphin 5283:Opiorphin 5266:Hemorphin 5025:Suffering 4994:Cordotomy 4984:Analgesia 4805:Allodynia 4785:Neuralgia 4749:Bone pain 4700:Toothache 4528:0362-4331 4501:207745183 4452:207357396 1083:, and/or 1077:serotonin 1026:serotonin 1010:protozoan 924:serotonin 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