Denervation of nasal mucosa induced by posterior nasal neurectomy suppresses nasal secretion, not hypersensitivity, in an allergic rhinitis rat model

Abstract

The posterior nasal nerve is the dominant source of the parasympathetic, sympathetic, and sensory fibers that innervate the nasal respiratory mucosa. Therefore, a posterior nasal neurectomy (PNN) is thought to induce denervation of the nasal mucosa and relieve the nasal symptoms of allergic rhinitis. However, the underlying mechanisms and therapeutic action of PNN remain unknown. To investigate the impact of PNN-induced denervation of the nasal mucosa on allergic rhinitis, we developed a rat model of PNN and examined the effects of PNN on allergic rhinitis in ovalbumin-sensitized rats. This rat model of PNN was characterized by the depletion of nerve fibers, choline acetyltransferase, and neuropeptides (eg, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and neuropeptide Y) in the nasal respiratory mucosa. These animals exhibited nasal gland and goblet cell hypertrophy in the septal mucosa and atrophy of the submucosal gland in the lateral nasal wall, as well as reduced nasal secretion due to deficient acetylcholine synthesis. In an ovalbumin-sensitized model of allergic rhinitis, PNN also induced the depletion of nerve fibers, choline acetyltransferase, and neuropeptides in the nasal mucosa and suppressed nasal secretion. However, PNN did not affect mucosal thickening, eosinophil and mast cell infiltration, interleukin-4 and interferon-γ mRNA expression, and allergic symptoms (ie, sneezing and nasal scratching). These results suggest that the peripheral nerves and corresponding neuropeptides regulate nasal secretion, but not hypersensitivity, in allergic rhinitis, and that allergic rhinitis-related mucosal reactions occur in a highly denervated mucosa after PNN. Posterior nasal neurectomy may be a therapeutic option for the treatment of hyperrhinorrhea, but not allergic rhinitis hypersensitivity. Allergic rhinitis is among the most common diseases; affecting 10-30% of people in industrialized countries. [1][2][3] This condition presents with symptoms that reduce the quality of life such as rhinorrhea, sneezing, nasal obstruction, and nasal itching. 4 Medical allergic rhinitis treatment is approached in a stepwise manner and includes agents such as antihistamines and nasal topical steroids. 1,2,5 However, for patients with allergic rhinitis refractory to medication therapy; surgical interventions such as endoscopic posterior nasal neurectomy (PNN) have been attempted.Endoscopic PNN, which involves the intranasal severing of the posterior nasal nerve, is a common surgical treatment for allergic rhinitis in Asia. 2,6,7 The posterior nasal nerve, which is a peripheral branch of the vidian nerve, innervates the nasal cavity via the pterygopalatine ganglion, which comprises parasympathetic and sympathetic vidian nerve fibers and sensory nerve fibers from the trigeminal nerve. Therefore, PNN is expected to suppress nasal hypersecretion by blocking autonomic vidian nerve fibers, similar to vidian neurectomy (VN), as well as hypersensitivity by simultaneously blocking sensory nerve fibers. 6...

Cholinergic neuron‐like D‐U87 cells promote polarization of allergic rhinitis T‐helper 2 cells

“…Although increasing evidence indicates the importance of parasympathetic nerves in the immune function of patients with other systematic diseases, studies of neuroimmune regulation in the field of AR have rarely been reported. 11,16,[21][22][23] In the present study, by establishing an in-vitro neuroimmune coculture model of D-U87 neurons and CD4 + T cells, we observed that cholinergic neuron-like D-U87 cells promoted the polarization of CD4 + T cells from patients with AR toward Th2 cells, and inhibition of the cholinergic activity of D-U87 cells by IB decreased the preferential Th2 polarization by modulating Akt signaling. To facilitate investigation of the role of cholinergic nerve function in patients with AR, an in-vitro cholinergic neuron model must be established.…”

“…However, the mechanisms underlying the effects of parasympathetic nerves on immune cells in patients with AR are not clear. Although increasing evidence indicates the importance of parasympathetic nerves in the immune function of patients with other systematic diseases, studies of neuroimmune regulation in the field of AR have rarely been reported , , . ‐ In the present study, by establishing an in‐vitro neuroimmune coculture model of D‐U87 neurons and CD4 + T cells, we observed that cholinergic neuron‐like D‐U87 cells promoted the polarization of CD4 + T cells from patients with AR toward Th2 cells, and inhibition of the cholinergic activity of D‐U87 cells by IB decreased the preferential Th2 polarization by modulating Akt signaling.…”

“…Our previous studies showed that inhibition of cholinergic nerve hyperactivity using ipratropium bromide (IB), a nonselective muscarinic cholinergic receptor inhibitor, decreased expression of IL‐4 mRNA in the nasal mucosa of BALB/c mice , . However, in a recent study, Nishijima et al reported that the expression of IL‐4 and interferon‐γ (IFN‐γ) mRNAs was not altered in the nasal mucosa of Sprague‐Dawley rats after nasal posterior neurectomy . The discrepancy between these studies may be explained by the use of different research methods.…”

“…14,15 However, in a recent study, Nishijima et al reported that the expression of IL-4 and interferon-γ (IFN-γ ) mRNAs was not altered in the nasal mucosa of Sprague-Dawley rats after nasal posterior neurectomy. 16 The discrepancy between these studies may be explained by the use of different research methods. Thus, studies exploring reciprocal regulation between the neural and immune systems in patients with AR will provide important clarification of these controversial issues.…”

Neuroendocrine cells derived chemokine vasoactive intestinal polypeptide (VIP) in allergic diseases

“…sneezing and nasal scratching). The study points out that PNN may be a therapeutic option for management of hyperrhinorrhea, but not allergic rhinitis hypersensitivity as nerves and secreted neuropeptides regulate only nasal secretion, but not hypersensitivity in AR [123]. Recent literature on allergic rhinitis patients provided the first evidence of the association between VIP and CRTH2 receptor in eosinophil chemotaxis in these patients.…”