4 and SP6—was seen to restore sensory function by microarray analysis [46]. In this study, they found that extending the EA treatment time for SCI rats could result in more changes in gene expression. After EA stimulation, the gene expression of calcitonin gene-related polypeptide (CGRP) and neuropeptide Y (NPY) were up-regulated and func- tionally annotated with the recovery of sensory functions. Acupuncture treatment at ST36 has also been reported to reduce neuropathic pain. Using microarray analysis, opioid receptor sigma was one of diﬀerentially expressed genes and involved in opioid signaling which has been implicated in neuropathic pain and the analgesic eﬀects of EA at ST36 in neuropathic pain model rats [47]. Parkinson’s disease is a neurodegenerative disease caused by the death of dopaminergic neurons [48]. Several studies have performed acupuncture treatments on diﬀerent acu- points in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine- (MPTP-) induced Parkinson’s models. These models were used to evaluate the eﬀects of acupuncture treatment at the GB34 and LR3 acupoints by analyzing the transcrip- tional proﬁles from cervical spinal cord or brain bilateral striatal tissues [49, 50]. Among the genes downregulated by acupuncture treatment, proplatelet basic protein (Ppbp) was functionally annotated with cytokine-cytokine receptor interaction pathways, and cytotoxic T lymphocyte-associated protein 2 alpha (Ctla2a) was associated with a pathway relevant to Parkinson’s disease according to KEGG analysis [49]. Similar results were observed from substantia nigra tissue of MPTP mice following treatment at the GB34 acupoint [51]. In previous studies, myelin basic protein, a major constituent of the axonal myelin sheath, has been reported to be up-regulated in MPTP mice and Parkinson’s patients stimulated at the GB34 acupoint [52]. In the bilateral striatal tissue of mice brain following acupuncture at the GB34 and LR3 acupoints, the gene expression levels of gap junction alpha 4 protein (Gja4) and tubulin alpha 8 (Tuba8) were down-regulated and annotated with the cell communication and gap junction pathway, respectively. Furthermore, an up-regulated gene, neurotrophin-3 (Ntf3), was annotated with the mitogen-activated protein kinases (MAPK) signaling pathway [50]. 3.6. Immune Modulation and Allergic Rhinitis. Evidence from mouse models has demonstrated that EA or acupunc- ture stimulation at ST36 can modulate the immune response [53–55]. Two studies using a 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH) immunized mouse model have shown that gene expression patterns can change in the spleen [55] and hypothalamus [54] after EA treatment. Using Sprague Dawley (SD) rats, Kim et al. found that the genes altered following EA at ST36 play crucial roles in natural killer cell activation in spleen tissue [53]. However, the eﬀects of EA treatments remain diverse, partly because of variation in immune responses when triggered in diﬀerent types of tissues or models (e.g., DNP-KLH immunized mice versus SD rats). Acupuncture treatment has also demonstrated some eﬀectiveness against allergic rhinitis in clinical settings, Evidence-Based Complementary and Alternative Medicine presumably through immune modulation [56, 57]. Allergic rhinitis occurs when an allergen is inhaled and generates an immune response in an individual. Its symptoms can be reduced by acupuncture treatment at the EX-HN3, LI4, LI20, and ST36 acupoints [56]. The eﬀectiveness of the treatment could be accounted for by modulation of pro- and anti-inﬂammatory genes observed through microarray analyses of blood samples. Immune responses to allergic rhinitis may vary depending on types of allergen. Shiue et al. have used the Phadiatop (Ph) assay, an eﬀective screening tool that detects a diverse range of allergens, to demonstrate that patients with Ph-positive (+) and Ph- negative (−) allergic rhinitis display diﬀerent gene expression proﬁles after acupuncture treatment [57]. A hierarchical clustering analysis revealed that three gene groups—those for active immune response, regulatory T cell diﬀerential, and apoptosis—were diﬀerentially expressed in the Ph (+) and Ph (−) patients after treatment [57]. These results also indicate the importance of personalized medicine for future investigations. 4. Proteomic Studies of Acupuncture in Diseases Proteomic technologies, such as two-dimensional elec- trophoresis (2-DE), can screen for proteins diﬀerentially expressed between individuals responsive and nonresponsive to acupuncture treatments. These proteins were identiﬁed by various mass spectrometry (MS) techniques, and their related pathways were explored to determine the mechanism of the acupuncture treatments. The results clarify the relationships between diﬀerent acupoints and functions (Table 1). 4.1. Acute Ischemic Stroke. EA eﬃcacy has been studied by comparing levels of serum proteins in response to EA or drug treatments in acute ischemic stroke patients [11]. Patients were treated with EA at eight acupoints (MS6, BL10, GB20, LI4, PC6, B40, SP6, and ST36) once daily for ten consecutive days. The protein proﬁles were analyzed using 2- DE; SerpinG1 was up-regulated, while gelsolin, complement component 1 (C1), C3, C4B, and beta-2-glycoprotein I were all down-regulated. Other studies have indicated that platelet C4 expression is associated with acute ischemic stroke by comparing serum proteins from healthy individuals and ischemic stroke patients [58]. 4.2. Neuronal Diseases. Using matrix-assisted laser desorp- tion/ionization time-of-ﬂight mass spectroscopy (MALDI TOF-MS) and subsequent protein database mining, Li et al. identiﬁed ﬁfteen candidate proteins whose expression levels varied with acupuncture treatment for SCI [59]. Among them, annexin A5 (ANXA5) and collapsin response mod- iﬁer protein 2 (CRMP2) were determined to be beneﬁcial for neuronal survival and axonal regeneration. ANXA5 is a member of the annexin superfamily of calcium- and phospholipid-binding proteins, which are related to apop- tosis and inﬂammation [60]. CRMP2 is a member of the collapsin response mediator protein family and is expressed