Clinical Additive Effects and Neuroimmune Mechanisms of Acupuncture for Patients with Allergic Rhinitis: A Scoping Review

Background: Allergic rhinitis (AR) is a common chronic inflammatory disorder characterized by IgE-mediated allergic responses and increasingly recognized neuroimmune interactions involving sensory nerves, autonomic pathways, neuropeptides, and immune cells. Although acupuncture has been investigated as an adjunctive treatment for AR, existing evidence is distributed across clinical efficacy studies and preclinical mechanistic experiments. In particular, the additional clinical benefits of acupuncture when combined with conventional Western medical treatment and the potential neuroimmune mechanisms underlying its effects have not been comprehensively mapped within an integrated framework. Objectives: This scoping review aims to systematically identify, characterize, and map the available clinical and preclinical evidence on acupuncture for AR, with particular emphasis on two complementary aspects: 1.To characterize the additive clinical effects of acupuncture when administered alongside conventional Western medical treatment in patients with clearly defined AR phenotypes. 2.To map the potential neuroimmune mechanisms through which acupuncture may influence AR, based on experimental animal studies. By integrating clinical and preclinical evidence, this review will explore the potential links between acupuncture stimulation, neural signaling, immune regulation, and improvements in AR-related clinical and pathological manifestations. Methods: This review will follow the methodological framework developed by the Joanna Briggs Institute (JBI) for scoping reviews and will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Search strategy: A comprehensive literature search will be conducted in eight electronic databases: PubMed, Web of Science (WoS), Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, SinoMed, and the Chinese Scientific Journal Database (VIP). Studies published in English or Chinese will be considered. Each database will be searched from its inception to the date of the final search. The search strategy will combine controlled vocabulary and free-text terms related to allergic rhinitis and acupuncture, including their relevant synonyms and variations. Search terms will be adapted to the indexing characteristics of each database. Detailed search strategies for all databases will be provided in the final review. Eligibility criteria: Clinical and preclinical studies will be considered separately because of their distinct research characteristics and objectives. Clinical studies: Eligible clinical studies will include randomized controlled trials (RCTs) involving patients diagnosed with AR according to recognized diagnostic criteria and classified according to clearly defined clinical phenotypes, including intermittent or persistent disease and severity classifications where reported. Eligible interventions will include manual acupuncture, warm-needle acupuncture, electroacupuncture, and intranasal acupuncture administered in addition to conventional Western medical treatment. Control groups will receive the corresponding conventional medical treatment without acupuncture. Clinical outcomes of interest will include nasal symptoms, quality of life, medication use, nasal physiological function, persistence of treatment effects, and human neuroimmune- or immunoinflammatory-related biomarkers. Preclinical studies: Eligible preclinical studies will involve experimentally induced animal models of AR in which acupuncture is used as an intervention and an appropriate control group is included. Because experimental AR models cannot be directly classified according to human clinical phenotypes and are generally not conducted against standardized conventional pharmacological treatment backgrounds, no restrictions will be imposed on specific clinical AR classifications or concomitant Western medical treatment in the preclinical component. Relevant outcomes will include disease-related phenotypes, neural structures and functional responses, neurotransmitters, neuropeptides, immune cell populations, inflammatory mediators, and associated molecular signaling pathways. Exclusion criteria: Studies published in languages other than English or Chinese, review articles, case reports, observational studies, non-randomized clinical studies, studies without an appropriate AR diagnosis or experimental AR model, studies without an acupuncture intervention, and studies lacking relevant outcomes will be excluded. Study selection: All records retrieved from the eight databases will be imported into EndNote reference management software. Duplicate records will be identified and removed before screening. Two reviewers will independently conduct study selection in two stages. First, titles and abstracts will be screened against the predefined eligibility criteria. Subsequently, the full texts of potentially eligible studies will be assessed for final inclusion. Disagreements between reviewers will be resolved through discussion, with consultation of a third reviewer if necessary. The study selection process and reasons for full-text exclusion will be documented and presented using a PRISMA flow diagram. Data charting: A standardized data extraction form will be developed to collect relevant information from the included studies. Clinical and preclinical studies will be charted separately. For clinical studies, extracted data will include publication characteristics, AR phenotype, diagnostic criteria, sample size, acupuncture modality, acupoints, stimulation parameters, treatment frequency and duration, background conventional treatment, comparator interventions, clinical outcomes, and neuroimmune-related biomarkers. For preclinical studies, extracted data will include publication characteristics, animal species, AR induction methods, acupuncture modality, acupoints, stimulation parameters, intervention duration, control conditions, disease-related phenotypes, neural structures and functions, neurotransmitters, neuropeptides, immune cell populations, inflammatory mediators, and associated signaling pathways. Particular attention will be given to experimental approaches used to investigate mechanistic causality, including neural blockade, receptor antagonism, genetic or functional manipulation, exogenous neurotransmitter administration, and rescue experiments. Evidence synthesis: Clinical and preclinical findings will be synthesized separately using descriptive and narrative approaches. Clinical evidence will be organized according to AR phenotype, acupuncture modality, conventional treatment background, and outcome domain, with an emphasis on the additional benefits of acupuncture beyond conventional medical treatment. Preclinical evidence will be organized according to the proposed neuroimmune sequence linking acupuncture stimulation, neural responses, neurotransmitter and neuropeptide signaling, immune regulation, inflammatory pathways, and disease-related phenotypes. Mechanistic evidence will be differentiated according to its level of experimental support, including downstream immune changes alone, neuroanatomical or neurochemical associative evidence, and causal evidence supported by neural or receptor blockade, functional manipulation, mimetic interventions, or rescue experiments. Given the anticipated heterogeneity in clinical populations, intervention modalities, animal models, and outcome measures, findings will be synthesized descriptively and narratively rather than through quantitative meta-analysis. No formal methodological quality appraisal or risk-of-bias assessment is planned, as the primary objective of this scoping review is to map the breadth, characteristics, and mechanistic depth of the available evidence. Expected outcomes and significance: This review is expected to provide an integrated evidence map of the clinical additive effects and potential neuroimmune mechanisms of acupuncture for AR. It will characterize the available evidence regarding the benefits of acupuncture as an adjunct to conventional treatment, identify the neuroimmune pathways investigated in experimental AR models, and distinguish associative mechanistic findings from evidence supported by functional or causal validation. The findings will help identify current knowledge gaps between clinical observations and experimental mechanisms, inform the design of future mechanistic studies and clinical trials, and provide an evidence-based foundation for optimizing the clinical application of acupuncture in AR.