neurokinin-a and Nasal-Obstruction

This prospective research study was designed to analyze the surgical outcomes and the intensity of substance P (SP), neurokinin A (NA), and calcitonin gene-related peptide (CGRP) in contact and noncontact nasal mucosa of patients with headache.. Twenty adults with secondary headache and correctible nasal obstruction were included in this study. The patients had nasal contact points between the nasal septum and the middle or inferior turbinates on nasal endoscopy and computed tomography scan. During surgical procedures, sample tissues were obtained from the nasal contact point and the noncontact area of the lateral nasal wall of these patients. Fluorescein staining intensity for antibodies against SP, NA, and CGRP was analyzed using image J software. Headaches were evaluated using a visual analog scale preoperatively and postoperatively.. The differences between the preoperative and the postoperative 3rd month (P < 0.001) and 12th month (P < 0.001) visual analog scale scores were statistically significant. However, fluorescein staining intensity for SP (P = 0.631), NA (P = 0.546), and CGRP (P = 0.683) did not show statistically significant differences between the contact mucosa and the noncontact mucosa groups.. Although in selected patients significant relief of headache can be obtained by surgery, there is no evidence from this study that SP, NA, and CGRP are responsible for the initiation of headache.

Topics: Adolescent; Adult; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Endoscopy; Female; Headache Disorders, Secondary; Humans; Male; Middle Aged; Nasal Mucosa; Nasal Obstruction; Nasal Septum; Neurokinin A; Prospective Studies; Substance P; Turbinates; Young Adult

Although it has been suggested that the use of tachykinin receptor antagonists might prove to be an effective treatment for allergic rhinitis (AR), they are not used clinically. Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model.. To evaluate newly developed tachykinin receptor antagonists in a Japanese cedar pollen-induced AR model and to determine their effect on allergen-induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR).. Sensitized guinea-pigs were challenged by forced inhalation of pollen once every week. Sneezing and nasal blockage were observed after pollen challenges. NHR (nasal blockage) to an intranasal application of leukotriene D(4) was assessed 2 days after an antigen challenge. We also evaluated whether intranasal dosing with a tachykinin causes NHR. NK(1) and NK(2) receptor antagonists were administered before an intranasal treatment with antigen or tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were measured by an enzyme immunoassay.. Although an NK(1) and NK(2) receptor dual antagonist showed no effect on pollen-induced sneezing and biphasic nasal blockage, it did completely suppress the development of NHR. Experiments using specific NK(1) or NK(2) receptor antagonists revealed that NK(2) receptor activation was preferentially involved in the development of hyperresponsiveness. Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal tissue were noted 20 min-1 h after the challenge. Intranasal instillation of either SP or NKA-induced NHR, which was almost completely inhibited by NK(2) receptor antagonists and partially inhibited by NK(1) receptor antagonists.. SP and NKA, which are released early after the challenge, mediate the development of NHR by preferentially activating NK(2) receptors. Therefore, NK(2) receptor antagonists might prove to be effective treatment of AR.

Topics: Allergens; Animals; Disease Models, Animal; Guinea Pigs; Humans; Nasal Lavage Fluid; Nasal Obstruction; Nasal Provocation Tests; Neurokinin A; Nose; Pollen; Receptors, Neurokinin-2; Receptors, Tachykinin; Rhinitis, Allergic, Seasonal; Sneezing; Substance P; Tachykinins

In airway tissues, it has been suggested that tachykinins act as the transmitter for afferent sensory nerves which respond to various irritants and may be involved in airway allergic reactions. Three classes of tachykinin receptor have been recognized, denoted NK1, NK2 and NK3, which exhibit preferential affinity for substance P, neurokinin A and neurokinin B, respectively. We used molecular probes to study the gene expression and distribution of NK2 receptor in human nasal mucosa. Total RNA was isolated from human nasal mucosa and NK2 receptor mRNA was detected in these tissues using reverse transcriptase polymerase chain reaction (RT-PCR). For an in situ hybridization study of human nasal mucosa, we utilized the PCR directly to incorporate a T7 RNA polymerase promoter sequence onto the NK2 receptor cDNA, and these PCR products were used as the DNA template for producing digoxigenin-labeled antisense and sense RNA probes. These studies revealed that NK2 receptor mRNA was expressed in blood vessels. The results suggest a primary role for neurokinin A in the form of vascular responses in the upper respiratory tract.

Topics: Gene Expression Regulation; Humans; In Situ Hybridization; Molecular Sequence Data; Nasal Mucosa; Nasal Obstruction; Neurokinin A; Receptors, Neurokinin-2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Turbinates

The purposes of the present study were i) to determine whether neuropeptides induce the nasal obstruction in guinea pigs, and ii) to examine the possible involvement of neuropeptides in allergic nasal obstruction. The decrease in nasal cavity volume was determined by acoustic rhinometry as an index of nasal obstruction. In non-sensitized guinea pigs, substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) caused the nasal obstruction 10 to 30 min after their intranasal application. LY303870 (1 mg/kg), a tachykinin NK1-receptor antagonist; SR48968 (1 mg/kg), a tackykinin NK2-receptor antagonist; and CGRP(8-37) (50 nmol/kg), a CGRP1-receptor antagonist, administered intravenously before the intranasal application of the neuropeptides, inhibited the responses induced by SP, NKA and CGRP, respectively. In the guinea pigs sensitized with dinitrophenyl-coupled Ascaris suum allergenic extract, the intranasal antigen challenge caused nasal obstruction. The response was biphasic and consisted of the early phase response (EPR) and the late phase response (LPR), which developed 30 min and 6 h, respectively, after the antigen challenge. Intravenous administration of LY303870 (1 mg/kg) before the antigen challenge inhibited the EPR, while those of SR48968 (1 mg/kg) and CGRP(8-37) (50 nmol/kg) inhibited the LPR. The present results suggest that neuropeptides are involved in the allergic nasal obstruction.

Topics: Animals; Calcitonin Gene-Related Peptide; Guinea Pigs; Hypersensitivity; Male; Miotics; Nasal Cavity; Nasal Obstruction; Neurokinin A; Neuropeptides; Peptide Fragments; Rhinitis; Substance P