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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Neurol.</journal-id>
<journal-title>Frontiers in Neurology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Neurol.</abbrev-journal-title>
<issn pub-type="epub">1664-2295</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fneur.2023.1266712</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Neurology</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Efficacy of cupping therapy on pain outcomes: an evidence-mapping study</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Liaoyao</given-names>
</name>
<xref rid="aff1" ref-type="aff"><sup>1</sup></xref>
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<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/methodology/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cai</surname>
<given-names>Ziling</given-names>
</name>
<xref rid="aff1" ref-type="aff"><sup>1</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Li</surname>
<given-names>Xuanlin</given-names>
</name>
<xref rid="aff1" ref-type="aff"><sup>1</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1067356/overview"/>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Zhu</surname>
<given-names>Aisong</given-names>
</name>
<xref rid="aff1" ref-type="aff"><sup>1</sup></xref>
<xref rid="aff2" ref-type="aff"><sup>2</sup></xref>
<xref rid="aff3" ref-type="aff"><sup>3</sup></xref>
<xref rid="c001" ref-type="corresp"><sup>&#x002A;</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>School of Basic Medical Sciences, Zhejiang Chinese Medical University</institution>, <addr-line>Hangzhou</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Key Laboratory of Blood-Stasis-Toxin Syndrome of Zhejiang Province</institution>, <addr-line>Hangzhou</addr-line>, <country>China</country></aff>
<aff id="aff3"><sup>3</sup><institution>Zhejiang Engineering Research Center for &#x201C;Preventive Treatment&#x201D; Smart Health of Traditional Chinese Medicine</institution>, <addr-line>Hangzhou</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0001"><p>Edited by: Michael Furian, Swiss TCM University, Switzerland</p></fn>
<fn fn-type="edited-by" id="fn0002"><p>Reviewed by: Hua Jiang, Guangxi Medical University, China; Chien-Liang Chen, I-Shou University, Taiwan</p></fn>
<corresp id="c001">&#x002A;Correspondence: Aisong Zhu, <email>liaoningzhongyi@hotmail.com</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>26</day>
<month>10</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="collection">
<year>2023</year>
</pub-date>
<volume>14</volume>
<elocation-id>1266712</elocation-id>
<history>
<date date-type="received">
<day>25</day>
<month>07</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>03</day>
<month>10</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2023 Wang, Cai, Li and Zhu.</copyright-statement>
<copyright-year>2023</copyright-year>
<copyright-holder>Wang, Cai, Li and Zhu</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec id="sec1">
<title>Objective</title>
<p>Cupping therapy is an ancient technique of healing used to treat a variety of ailments. An evidence-mapping study was conducted to summarize the existing evidence of cupping therapy for pain-related outcomes and indicate the effect and the quality of evidence to provide a comprehensive view of what is known.</p>
</sec>
<sec id="sec2">
<title>Methods</title>
<p>PubMed, Cochrane Library, Embase, and Web of Science were searched to collect the meta-analyses investigating the association between cupping therapy and pain-related outcomes. The methodological quality was assessed by using the AMSTAR 2 tool. Significant outcomes (<italic>p</italic>&#x2009;&#x003C;&#x2009;0.05) were assessed using the GRADE system. The summary of evidence is presented by bubble plots and human evidence mapping.</p>
</sec>
<sec id="sec3">
<title>Results</title>
<p>Fourteen meta-analyses covering five distinct pain-related conditions were identified and assessed for methodological quality using the AMSTAR 2, which categorized the quality as critically low (36%), low (50.0%), moderate (7%), and high (7%). In accordance with the GRADE system, no high-quality evidence was found that demonstrates the efficacy of cupping therapy for pain-related outcomes. Specifically, for neck pain, there were two moderate-quality, four low-quality, and two very low-quality evidence, while only one very low-quality evidence supports its efficacy in treating herpes zoster and one low-quality evidence for chronic back pain. Additionally, for low back pain, there were two moderate-quality, one low-quality, and four very low-quality evidence, and for knee osteoarthritis, three moderate-quality evidence suggest that cupping therapy may alleviate pain score.</p>
</sec>
<sec id="sec4">
<title>Conclusion</title>
<p>The available evidence of very low-to-moderate quality suggests that cupping therapy is effective in managing chronic pain, knee osteoarthritis, low back pain, neck pain, chronic back pain, and herpes zoster. Moreover, it represents a promising, safe, and effective non-pharmacological therapy that warrants wider application and promotion.</p>
<p><bold>Systematic review registration</bold>: <ext-link xlink:href="https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255879" ext-link-type="uri">https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255879</ext-link>, identifier: CRD42021255879.</p>
</sec>
</abstract>
<kwd-group>
<kwd>cupping therapy</kwd>
<kwd>pain-related conditions</kwd>
<kwd>systematic review</kwd>
<kwd>meta-analysis</kwd>
<kwd>evidence mapping</kwd>
</kwd-group>
<counts>
<fig-count count="4"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="43"/>
<page-count count="10"/>
<word-count count="5727"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Experimental Therapeutics</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec5">
<label>1.</label>
<title>Introduction</title>
<p>The definition of pain has been revised to an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage according to the International Association for the Study of Pain (IASP) (<xref ref-type="bibr" rid="ref1">1</xref>). Pain is the principal reason why individuals seek medical care, with three of the top ten reasons being osteoarthritis, back pain, and headaches (<xref ref-type="bibr" rid="ref2">2</xref>). Chronic pain poses a significant personal and economic burden, affecting over 30% of the global population and causing psychological distress and sleep issues (<xref ref-type="bibr" rid="ref3">3</xref>). The Global Burden of Diseases study identified low back pain and migraine as two of the five leading causes of years lived with disability (YLDs) (<xref ref-type="bibr" rid="ref4">4</xref>). In China, the annual total treatment cost of chronic pain may surpass 500 billion yuan (approximately 685 billion dollars) (<xref ref-type="bibr" rid="ref5">5</xref>). Although many medications may have limited effectiveness, they often come with significant side effects that can be compounded (<xref ref-type="bibr" rid="ref6">6</xref>). As a result, alternative complementary treatments are increasingly crucial in the management of pain-related conditions. The demand for complementary and integrative medicine approaches has been on the rise, including mind&#x2013;body interventions, acupuncture therapy, and other traditional Chinese medicine (TCM) practices (<xref ref-type="bibr" rid="ref7">7</xref>). Among these, cupping therapy stands out due to its simplicity, safety, and efficacy. Cupping therapy has been widely used in various fields of medicine, including internal medicine, external medicine, gynecology, pediatrics, and particularly in conditions related to pain, skin diseases, knee osteoarthritis, migraines, and other ailments (<xref ref-type="bibr" rid="ref8">8</xref>).</p>
<p>Cupping therapy, an ancient healing modality, has long been a mainstay in TCM, as well as being documented in the historical records of other regions, including ancient Egypt, Greece, and India. This valuable therapeutic technique has been utilized for thousands of years, and its benefits have been recognized and applied worldwide. It is not only a part of TCM but also recorded in ancient Egypt, Greece, India, and other regions. It is a precious asset to people and has been used worldwide. Cupping therapy involves the application of cups to targeted acupoints or specific skin regions, which creates a negative pressure (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref10">10</xref>). The modalities of cupping can be broadly classified into dry cupping, wet cupping, massage cupping, etc. (<xref ref-type="bibr" rid="ref11">11</xref>).</p>
<p>Cupping therapy, initially used as a pain relief method, has now been extended to a broad range of medical conditions (<xref ref-type="bibr" rid="ref12">12</xref>). Recent evidence shows that this therapy may offer potential benefits for a variety of conditions such as myofascial pain (<xref ref-type="bibr" rid="ref13">13</xref>), low back pain, ankylosing spondylitis, knee osteoarthritis, neck pain, herpes zoster, migraine, plaque psoriasis, and chronic urticaria (<xref ref-type="bibr" rid="ref14">14</xref>). For pain-related conditions, cupping might be used as a useful intervention because it decreases the pain level and improves blood flow to the affected area with low adverse effects (<xref ref-type="bibr" rid="ref15">15</xref>). A clinical study has confirmed that cupping was more effective in improving pain and functional disability in people with persistent non-specific low back pain when compared to sham therapy (<xref ref-type="bibr" rid="ref16">16</xref>). A single session of dry cupping therapy may be an effective short-term treatment method for immediately reducing pain (<xref ref-type="bibr" rid="ref17">17</xref>). However, it is worth noting that there exist clinical research findings that do not align with this conclusion. Cupping therapy was not superior to sham cupping for improving pain, physical function, mobility, quality of life, psychological symptoms, or medication use in people with non-specific chronic low back pain (<xref ref-type="bibr" rid="ref18">18</xref>). Despite this, the National Center for Complementary and Integrative Health (NCCIH) (U.S.) states that although cupping therapy may have some effect in reducing pain, the available evidence is currently insufficient (<xref ref-type="bibr" rid="ref19">19</xref>). Moreover, although research on this form of therapy has increased, there remains a lack of comprehensive surveys that summarize the efficacy of cupping therapy in managing pain-related conditions. To bridge this gap, the present study endeavors to furnish a comprehensive evaluation of related meta-analyses pertaining to cupping therapy, with a particular focus on the outcomes of pain, as well as to carry out evidence mapping. The primary aim of this study was to provide insights for forthcoming research endeavors.</p>
</sec>
<sec sec-type="methods" id="sec6">
<label>2.</label>
<title>Methods</title>
<sec id="sec7">
<label>2.1.</label>
<title>Protocol and registration</title>
<p>The protocol of this evidence mapping was registered at the PROSPERO (CRD 42021255879).</p>
</sec>
<sec id="sec8">
<label>2.2.</label>
<title>Data sources and search strategy</title>
<p>PubMed, Cochrane Library, Embase, and Web of Science were searched to identify the systematic reviews with meta-analyses on the relationship between cupping therapy and any pain-related conditions published from inception until 15 April 2023. Medical Subject Heading (MeSH) terms and their variants were used for the search strategy for the following terms: &#x201C;cupping therapy,&#x201D; &#x201C;cupping,&#x201D; &#x201C;cupping treatment,&#x201D; &#x201C;meta-analysis,&#x201D; &#x201C;meta-analysis as topic,&#x201D; &#x201C;systematic review.&#x201D; Only published articles in English were considered. We also conducted an extensive review of the pertinent literature, encompassing a range of narrative synopses within the domain. Such a comprehensive approach allowed us to ensure that no substantive sources were overlooked. The details of the search strategies for all databases are given in <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S1</xref>.</p>
</sec>
<sec id="sec9">
<label>2.3.</label>
<title>Inclusion and exclusion criteria</title>
<p>All systematic reviews with meta-analysis related to cupping therapy (including but not limited to dry cupping, wet cupping, moving cupping, etc.) for any pain-related outcomes were included. Conference abstracts, letters, protocols, overviews, and systematic reviews without quantitative meta-analysis were excluded.</p>
</sec>
<sec id="sec10">
<label>2.4.</label>
<title>Study selection</title>
<p>All records identified from four databases were imported into Endnote X9 software, and duplicate records removed before screening. After eliminating duplicates, two authors (LW and XL) independently read the titles, abstracts, or full text until all studies are confirmed. Ambiguity was resolved by group discussion.</p>
</sec>
<sec id="sec11">
<label>2.5.</label>
<title>Data extraction</title>
<p>For each eligible study, two authors (LW and ZC) extracted the following data independently: first author, publication year, country, study type, type of disease or disorder, number of studies, sample size, intervention, comparison, outcome, type of metric with 95% confidence interval [CI] (i.e., odds ratio [OR], relative risk [RR], risk ratio [HR], standardized mean deviation [SMD], mean deviation [MD]), adverse effect, and the main findings. Ambiguity was resolved by group discussion with the other author (AZ).</p>
</sec>
<sec id="sec12">
<label>2.6.</label>
<title>Methodological quality assessment</title>
<p>A measurement tool to assess systematic reviews 2 (AMSTAR 2) (<xref ref-type="bibr" rid="ref20">20</xref>), which contains 16 items, was used to assess the methodological quality and ranks the quality from critical low to high of the included studies. Two researchers (LW and ZC) independently evaluated the quality of the included studies. The items of the AMSTAR 2 checklist are shown in <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S2</xref>.</p>
</sec>
<sec id="sec13">
<label>2.7.</label>
<title>Evidence quality assessment</title>
<p>We used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) (<xref ref-type="bibr" rid="ref21">21</xref>) to assess the quality of evidence for each outcome on four degrees (high, moderate, low, and very low quality) by two reviewers (LW and XL) independently. Any disagreement between reviewers was resolved by discussion, and consistent results were reached finally.</p>
</sec>
<sec id="sec14">
<label>2.8.</label>
<title>Evidence mapping presentation</title>
<p>The evidence mapping findings were depicted using bubble plots in a graphical form. Each bubble in the chart denotes clinical evidence from studies that explored the efficacy of cupping for specific pain-related conditions and clinical indications. Excel 2021 was utilized to design the evidence mapping. The X-axis indicates the effect size of the primary outcome visual analog scale (VAS) (<italic>p</italic> &#x003C; 0.05), while the Y-axis denotes the number of articles. The size of the bubbles corresponds to the total population&#x2019;s sample size for the effects of cupping, with bigger bubbles representing a larger sample size. The colors symbolize the different interventions of cupping and non-cupping groups. In addition, we aimed to summarize all the distinct qualities of evidence relating to different pain conditions in human evidence mapping.</p>
</sec>
</sec>
<sec sec-type="results" id="sec15">
<label>3.</label>
<title>Results</title>
<sec id="sec16">
<label>3.1.</label>
<title>Study selection</title>
<p>A total of 265 records were identified. After removing duplicates and screening the titles and abstracts, there were 19 potentially eligible studies. We finally included 14 studies (<xref ref-type="bibr" rid="ref22 ref23 ref24 ref25 ref26 ref27 ref28 ref29 ref30 ref31 ref32 ref33 ref34 ref35">22&#x2013;35</xref>) after assessing for eligibility including five types of pain-related conditions. The study selection process is shown in <xref rid="fig1" ref-type="fig">Figure 1</xref>.</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Flow chart of the literature search and screening process.</p>
</caption>
<graphic xlink:href="fneur-14-1266712-g001.tif"/>
</fig>
</sec>
<sec id="sec17">
<label>3.2.</label>
<title>Study characteristics</title>
<p>Five studies (<xref ref-type="bibr" rid="ref23">23</xref>, <xref ref-type="bibr" rid="ref26">26</xref>, <xref ref-type="bibr" rid="ref28">28</xref>, <xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref31">31</xref>) contained less than ten original studies, while twelve (85.7%) studies (<xref ref-type="bibr" rid="ref23 ref24 ref25 ref26 ref27 ref28 ref29 ref30">23&#x2013;30</xref>, <xref ref-type="bibr" rid="ref32 ref33 ref34 ref35">32&#x2013;35</xref>) had a combined total sample of over 500 participants. The majority of studies, eight (57.1%) in total (<xref ref-type="bibr" rid="ref23">23</xref>, <xref ref-type="bibr" rid="ref26">26</xref>, <xref ref-type="bibr" rid="ref29 ref30 ref31">29&#x2013;31</xref>, <xref ref-type="bibr" rid="ref33 ref34 ref35">33&#x2013;35</xref>), were conducted in China, followed by two (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref28">28</xref>) in Korea, and one each in Germany (<xref ref-type="bibr" rid="ref24">24</xref>), Brazil (<xref ref-type="bibr" rid="ref27">27</xref>), Australia (<xref ref-type="bibr" rid="ref32">32</xref>), and Iran (<xref ref-type="bibr" rid="ref22">22</xref>). The included studies investigated various conditions, including low back pain (<italic>n</italic>&#x2009;=&#x2009;4), neck pain (<italic>n</italic>&#x2009;=&#x2009;3), knee osteoarthritis (<italic>n</italic>&#x2009;=&#x2009;2), chronic back pain (<italic>n</italic>&#x2009;=&#x2009;1), migraine (<italic>n</italic>&#x2009;=&#x2009;1), chronic pain (<italic>n</italic>&#x2009;=&#x2009;1), pain-related conditions (<italic>n</italic>&#x2009;=&#x2009;1), musculoskeletal pain (<italic>n</italic>&#x2009;=&#x2009;1), and herpes zoster (<italic>n</italic>&#x2009;=&#x2009;1). The characteristics of included studies are shown in <xref rid="tab1" ref-type="table">Table 1</xref>.</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Characteristics of included studies.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Study</th>
<th align="left" valign="top">Country</th>
<th align="left" valign="top">Clinical condition</th>
<th align="center" valign="top">No. of databases searched</th>
<th align="center" valign="top">No. of studies</th>
<th align="center" valign="top">No. of participants</th>
<th align="left" valign="top">Outcome</th>
<th align="left" valign="top">Tool for risk of bias assessment</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Cramer et al. (<xref ref-type="bibr" rid="ref24">24</xref>)</td>
<td align="left" valign="top">Germany</td>
<td align="left" valign="top">Chronic pain</td>
<td align="center" valign="top">3</td>
<td align="center" valign="top">18</td>
<td align="center" valign="top">1,172</td>
<td align="left" valign="top">Pain intensity</td>
<td align="left" valign="top">ROB tool</td>
</tr>
<tr>
<td align="left" valign="top">Moura et al. (<xref ref-type="bibr" rid="ref27">27</xref>)</td>
<td align="left" valign="top">Brazil</td>
<td align="left" valign="top">Chronic back pain</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">16</td>
<td align="center" valign="top">1,049</td>
<td align="left" valign="top">Pain intensity score</td>
<td align="left" valign="top">Jadad scale</td>
</tr>
<tr>
<td align="left" valign="top">Wang 2018 (<xref ref-type="bibr" rid="ref30">30</xref>)</td>
<td align="left" valign="top">China</td>
<td align="left" valign="top">Knee osteoarthritis</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">5</td>
<td align="center" valign="top">535</td>
<td align="left" valign="top">VAS, WOMAC-pain</td>
<td align="left" valign="top">ROB tool</td>
</tr>
<tr>
<td align="left" valign="top">Seo et al. (<xref ref-type="bibr" rid="ref28">28</xref>)</td>
<td align="left" valign="top">Korea</td>
<td align="left" valign="top">Migraine</td>
<td align="center" valign="top">8</td>
<td align="center" valign="top">6</td>
<td align="center" valign="top">510</td>
<td align="left" valign="top">VAS</td>
<td align="left" valign="top">ROB tool</td>
</tr>
<tr>
<td align="left" valign="top">Li et al. (<xref ref-type="bibr" rid="ref26">26</xref>)</td>
<td align="left" valign="top">China</td>
<td align="left" valign="top">Knee osteoarthritis</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">661</td>
<td align="left" valign="top">VAS, WOMAC-pain</td>
<td align="left" valign="top">ROB tool</td>
</tr>
<tr>
<td align="left" valign="top">Zhang et al. (<xref ref-type="bibr" rid="ref35">35</xref>)</td>
<td align="left" valign="top">China</td>
<td align="left" valign="top">Pain-related conditions</td>
<td align="center" valign="top">6</td>
<td align="center" valign="top">23</td>
<td align="center" valign="top">2,845</td>
<td align="left" valign="top">VAS</td>
<td align="left" valign="top">ROB tool</td>
</tr>
<tr>
<td align="left" valign="top">Wood et al. (<xref ref-type="bibr" rid="ref32">32</xref>)</td>
<td align="left" valign="top">Australia</td>
<td align="left" valign="top">Musculoskeletal pain</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">21</td>
<td align="center" valign="top">1,049</td>
<td align="left" valign="top">VAS, NRS, SMPQ, PPT</td>
<td align="left" valign="top">Downs &#x0026; Black (D&#x0026;B) quality assessment scale</td>
</tr>
<tr>
<td align="left" valign="top">Kim et al. (<xref ref-type="bibr" rid="ref25">25</xref>)</td>
<td align="left" valign="top">Korea</td>
<td align="left" valign="top">Neck pain</td>
<td align="center" valign="top">9</td>
<td align="center" valign="top">18</td>
<td align="center" valign="top">1,683</td>
<td align="left" valign="top">VAS, NPQ</td>
<td align="left" valign="top">ROB tool</td>
</tr>
<tr>
<td align="left" valign="top">Wang et al. (<xref ref-type="bibr" rid="ref31">31</xref>)</td>
<td align="left" valign="top">China</td>
<td align="left" valign="top">Low back pain</td>
<td align="center" valign="top">3</td>
<td align="center" valign="top">6</td>
<td align="center" valign="top">458</td>
<td align="left" valign="top">VAS, MPPI</td>
<td align="left" valign="top">Jadad scale</td>
</tr>
<tr>
<td align="left" valign="top">Azizkhani et al. (<xref ref-type="bibr" rid="ref22">22</xref>)</td>
<td align="left" valign="top">Iran</td>
<td align="left" valign="top">Non-specific neck pain</td>
<td align="center" valign="top">10</td>
<td align="center" valign="top">10</td>
<td align="center" valign="top">441</td>
<td align="left" valign="top">VAS</td>
<td align="left" valign="top">ROB tool</td>
</tr>
<tr>
<td align="left" valign="top">Cao et al. (<xref ref-type="bibr" rid="ref23">23</xref>)</td>
<td align="left" valign="top">China</td>
<td align="left" valign="top">Herpes zoster</td>
<td align="center" valign="top">5</td>
<td align="center" valign="top">8</td>
<td align="center" valign="top">651</td>
<td align="left" valign="top">Number of patients with PHN after treatment</td>
<td align="left" valign="top">Agency for Healthcare Research and Quality</td>
</tr>
<tr>
<td align="left" valign="top">Yuan et al. (<xref ref-type="bibr" rid="ref34">34</xref>)</td>
<td align="left" valign="top">China</td>
<td align="left" valign="top">Neck Pain and Low Back Pain</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">11</td>
<td align="center" valign="top">666</td>
<td align="left" valign="top">VAS</td>
<td align="left" valign="top">Cochrane Back Review Group</td>
</tr>
<tr>
<td align="left" valign="top">Shen et al. (<xref ref-type="bibr" rid="ref29">29</xref>)</td>
<td align="left" valign="top">China</td>
<td align="left" valign="top">Low Back Pain</td>
<td align="center" valign="top">5</td>
<td align="center" valign="top">10</td>
<td align="center" valign="top">690</td>
<td align="left" valign="top">VAS, PPI</td>
<td align="left" valign="top">ROB tool</td>
</tr>
<tr>
<td align="left" valign="top">Xie et al. (<xref ref-type="bibr" rid="ref33">33</xref>)</td>
<td align="left" valign="top">China</td>
<td align="left" valign="top">Non-specific low back pain</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">13</td>
<td align="center" valign="top">1,088</td>
<td align="left" valign="top">VAS, NRS</td>
<td align="left" valign="top">ROB tool</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>MPPI, McGill present pain index; NPQ, Northwick Park Neck Pain Questionnaire; NRS, numerical rating scale; PHN, postherpetic neuralgia; PPI, present pain intensity; PPT, pain pressure threshold; ROB, risk of bias; SMPQ, Short Form McGill Pain Questionnaire; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec18">
<label>3.3.</label>
<title>Methodology quality</title>
<p>One high-quality study (<xref ref-type="bibr" rid="ref24">24</xref>) and one moderate-quality study (<xref ref-type="bibr" rid="ref26">26</xref>) were included. However, five studies (<xref ref-type="bibr" rid="ref22">22</xref>, <xref ref-type="bibr" rid="ref23">23</xref>, <xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref27">27</xref>, <xref ref-type="bibr" rid="ref32">32</xref>) were rated as critically low quality, and seven studies (<xref ref-type="bibr" rid="ref28 ref29 ref30 ref31">28&#x2013;31</xref>, <xref ref-type="bibr" rid="ref33 ref34 ref35">33&#x2013;35</xref>) were rated as low quality. The primary reasons for these downgraded ratings were noted as the absence of registration and protocols (item 2), poor information regarding the source of funding for the original studies in the systematic review and meta-analysis (item 10), and an inadequate explanation of the risk of bias when discussing the results of the review (item 13). The assessment of methodology quality of included studies by AMSTAR 2 is presented in <xref rid="fig2" ref-type="fig">Figure 2</xref>.</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>AMSTAR 2 quality assessment.</p>
</caption>
<graphic xlink:href="fneur-14-1266712-g002.tif"/>
</fig>
</sec>
<sec id="sec19">
<label>3.4.</label>
<title>Evidence quality</title>
<p>Among the 21 outcomes, the quality of evidence was rated as moderate quality, low quality, and very low quality. Eight moderate-quality evidence are for knee osteoarthritis (<italic>n</italic>&#x2009;=&#x2009;3), neck pain (<italic>n</italic>&#x2009;=&#x2009;2), low back pain (<italic>n</italic>&#x2009;=&#x2009;2), and chronic pain (<italic>n</italic>&#x2009;=&#x2009;1). Six low-quality evidence are for neck pain (<italic>n</italic>&#x2009;=&#x2009;4), chronic back pain (<italic>n</italic>&#x2009;=&#x2009;1), and low back pain (<italic>n</italic>&#x2009;=&#x2009;1). Seven very low-quality evidence are for low back pain (<italic>n</italic>&#x2009;=&#x2009;4), neck pain (<italic>n</italic>&#x2009;=&#x2009;2), and herpes zoster (<italic>n</italic>&#x2009;=&#x2009;1). On the basis of two moderate-quality, four low-quality, and two very low-quality evidence, cupping therapy is found to be effective for treating neck pain. Similarly, two moderate-quality, one low-quality, and four very low-quality evidence support the efficacy of cupping therapy in alleviating low back pain. Additionally, three moderate-quality evidence indicate that cupping therapy is useful in managing knee osteoarthritis, while only one very low-quality evidence supports its efficacy in treating herpes zoster and one low-quality evidence for chronic back pain. Furthermore, one moderate-quality evidence supports the use of cupping therapy in managing chronic pain. <xref rid="tab2" ref-type="table">Table 2</xref> and <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S3</xref> provide a detailed account of the GRADE assessment.</p>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>Evidence quality of cupping therapy and pain-related outcomes.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Study</th>
<th align="left" valign="top">Condition</th>
<th align="center" valign="top">NO. of studies</th>
<th align="center" valign="top">NO. of participants</th>
<th align="left" valign="top">Outcome</th>
<th align="left" valign="top">Metrics</th>
<th align="center" valign="top">ES (95%) CI</th>
<th align="center" valign="top">I<sup>2</sup> (%)</th>
<th align="left" valign="top">Comparison</th>
<th align="left" valign="top">Evidence quality</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Cramer et al. (<xref ref-type="bibr" rid="ref24">24</xref>)</td>
<td align="left" valign="middle">Chronic Pain</td>
<td align="center" valign="middle">13</td>
<td align="center" valign="middle">718</td>
<td align="left" valign="middle">Pain intensity</td>
<td align="left" valign="middle">SMD</td>
<td align="center" valign="middle">&#x2212;1.03 [&#x2212;1.41, &#x2212;0.65]</td>
<td align="center" valign="middle">81</td>
<td align="left" valign="middle">Cupping vs. no treatment</td>
<td align="left" valign="bottom">&#x2A01;&#x2A01;&#x2A01;&#x3007;Moderate</td>
</tr>
<tr>
<td align="left" valign="middle">Moura et al. (<xref ref-type="bibr" rid="ref27">27</xref>)</td>
<td align="left" valign="middle">Chronic back pain</td>
<td align="center" valign="middle">10</td>
<td align="center" valign="middle">595</td>
<td align="left" valign="middle">Pain intensity score</td>
<td align="left" valign="middle">AD</td>
<td align="center" valign="middle">&#x2212;1.59 [&#x2212;2.07, &#x2212;1.10]</td>
<td align="center" valign="middle">67.7</td>
<td align="left" valign="middle">Cupping therapy compared to one or more of the following groups: sham, active treatment, waiting list, standard medical treatment, or no treatment</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x3007;&#x3007;Low</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2">Wang et al. (<xref ref-type="bibr" rid="ref30">30</xref>)</td>
<td align="left" valign="top" rowspan="2">Knee osteoarthritis</td>
<td align="center" valign="top">2</td>
<td align="center" valign="top">211</td>
<td align="left" valign="top">VAS</td>
<td align="left" valign="top">MD</td>
<td align="center" valign="top">&#x2212;1.79 [&#x2212;2.40, &#x2212;1.18]</td>
<td align="center" valign="top">0</td>
<td align="left" valign="middle">Dry cupping therapy + Western medicine vs. Western medicine</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x2A01;&#x3007;Moderate</td>
</tr>
<tr>
<td align="center" valign="top">2</td>
<td align="center" valign="top">211</td>
<td align="left" valign="top">WOMAC- Pain</td>
<td align="left" valign="top">MD</td>
<td align="center" valign="top">&#x2212;0.73 [&#x2212;1.03, &#x2212;0.43]</td>
<td align="center" valign="top">0</td>
<td align="left" valign="middle">Dry cupping therapy + Western medicine vs. Western medicine</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x2A01;&#x3007;Moderate</td>
</tr>
<tr>
<td align="left" valign="middle">Li et al. (<xref ref-type="bibr" rid="ref26">26</xref>)</td>
<td align="left" valign="middle">Knee osteoarthritis</td>
<td align="center" valign="middle">2</td>
<td align="center" valign="middle">211</td>
<td align="left" valign="top">WOMAC- pain</td>
<td align="left" valign="middle">MD</td>
<td align="center" valign="middle">&#x2212;1.10 [&#x2212;1.61, &#x2212;0.41]</td>
<td align="center" valign="middle">0</td>
<td align="left" valign="middle">Dry cupping therapy + Western medicine vs. Western medicine</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x2A01;&#x3007;Moderate</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="4">Wood et al. (<xref ref-type="bibr" rid="ref32">32</xref>)</td>
<td align="left" valign="top" rowspan="2">Musculoskeletal pain (non-specific neck pain)</td>
<td align="center" valign="middle">5</td>
<td align="center" valign="middle">239</td>
<td align="left" valign="middle">VAS</td>
<td align="left" valign="middle">MD</td>
<td align="center" valign="middle">&#x2212;1.29 [&#x2212;2.05, &#x2212;0.53]</td>
<td align="center" valign="middle">94</td>
<td align="left" valign="middle">Dry cupping vs. no treatment</td>
<td align="left" valign="middle">&#x2A01;&#x3007;&#x3007;&#x3007;Very low</td>
</tr>
<tr>
<td align="center" valign="middle">4</td>
<td align="center" valign="middle">191</td>
<td align="left" valign="middle">PPT</td>
<td align="left" valign="middle">SMD</td>
<td align="center" valign="middle">&#x2212;0.40 [&#x2212;0.69, &#x2212;0.11]</td>
<td align="center" valign="middle">0</td>
<td align="left" valign="middle">Dry cupping vs. no treatment</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x3007;&#x3007;Low</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2">Musculoskeletal pain (low back pain)</td>
<td align="center" valign="middle">2</td>
<td align="center" valign="middle">196</td>
<td align="left" valign="middle">VAS</td>
<td align="left" valign="middle">MD</td>
<td align="center" valign="middle">&#x2212;19.38 [&#x2212;28.09, &#x2212;10.66]</td>
<td align="center" valign="middle">59</td>
<td align="left" valign="middle">Dry cupping vs. comparative or control group</td>
<td align="left" valign="middle">&#x2A01;&#x3007;&#x3007;&#x3007;Very low</td>
</tr>
<tr>
<td align="center" valign="middle">2</td>
<td align="center" valign="middle">160</td>
<td align="left" valign="middle">SMPQ</td>
<td align="left" valign="middle">MD</td>
<td align="center" valign="middle">&#x2212;11.20 [&#x2212;13.76, &#x2212;8.64]</td>
<td align="center" valign="middle">76</td>
<td align="left" valign="middle">Dry cupping vs. comparative or control group</td>
<td align="left" valign="middle">&#x2A01;&#x3007;&#x3007;&#x3007;Very low</td>
</tr>
<tr>
<td align="left" valign="middle" rowspan="4">Kim et al. (<xref ref-type="bibr" rid="ref25">25</xref>)</td>
<td align="left" valign="middle" rowspan="4">Neck pain</td>
<td align="center" valign="middle">5</td>
<td align="center" valign="middle">241</td>
<td align="left" valign="middle">VAS</td>
<td align="left" valign="middle">MD</td>
<td align="center" valign="middle">&#x2212;2.42 [&#x2212;3.98, &#x2212;0.86]</td>
<td align="center" valign="middle">93</td>
<td align="left" valign="middle">Cupping vs. no treatment</td>
<td align="left" valign="middle">&#x2A01;&#x3007;&#x3007;&#x3007;Very low</td>
</tr>
<tr>
<td align="center" valign="middle">9</td>
<td align="center" valign="middle">870</td>
<td align="left" valign="middle">VAS</td>
<td align="left" valign="middle">MD</td>
<td align="center" valign="middle">&#x2212;0.89 [&#x2212;1.42, &#x2212;0.37]</td>
<td align="center" valign="middle">88</td>
<td align="left" valign="middle">Cupping vs. active control</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x3007;&#x3007;Low</td>
</tr>
<tr>
<td align="center" valign="middle">1</td>
<td align="center" valign="middle">95</td>
<td align="left" valign="middle">NPQ</td>
<td align="left" valign="middle">MD</td>
<td align="center" valign="middle">3.59 [2.02, 5.16]</td>
<td align="center" valign="middle">/</td>
<td align="left" valign="middle">Cupping vs. active control</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x3007;&#x3007;Low</td>
</tr>
<tr>
<td align="center" valign="middle">5</td>
<td align="center" valign="middle">534</td>
<td align="left" valign="middle">VAS</td>
<td align="left" valign="middle">MD</td>
<td align="center" valign="middle">&#x2212;0.87 [&#x2212;1.14, &#x2212;0.61]</td>
<td align="center" valign="middle">19</td>
<td align="left" valign="middle">Cupping + active control vs. active control</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x2A01;&#x3007;Moderate</td>
</tr>
<tr>
<td align="left" valign="middle">Wang et al. (<xref ref-type="bibr" rid="ref31">31</xref>)</td>
<td align="left" valign="middle">Low back pain</td>
<td align="center" valign="middle">4</td>
<td align="center" valign="middle">280</td>
<td align="left" valign="middle">VAS</td>
<td align="left" valign="middle">SMD</td>
<td align="center" valign="middle">&#x2212;0.73 [&#x2212;1.42, &#x2212;0.04]</td>
<td align="center" valign="middle">87</td>
<td align="left" valign="middle">Cupping vs. medication or usual care</td>
<td align="left" valign="middle">&#x2A01;&#x3007;&#x3007;&#x3007;Very low</td>
</tr>
<tr>
<td align="left" valign="middle">Azizkhani et al. (<xref ref-type="bibr" rid="ref22">22</xref>)</td>
<td align="left" valign="middle">non-specific neck pain</td>
<td align="center" valign="middle">5</td>
<td align="center" valign="middle">282</td>
<td align="left" valign="middle">VAS</td>
<td align="left" valign="middle">MD</td>
<td align="center" valign="middle">&#x2212;0.84 [&#x2212;1.22, &#x2212;0.46]</td>
<td align="center" valign="middle">54.7</td>
<td align="left" valign="middle">Cupping therapy vs. other or no treatment</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x3007;&#x3007;Low</td>
</tr>
<tr>
<td align="left" valign="top">Cao et al. (<xref ref-type="bibr" rid="ref23">23</xref>)</td>
<td align="left" valign="top">Herpes zoster</td>
<td align="center" valign="top">3</td>
<td align="center" valign="top">326</td>
<td align="left" valign="middle">Number of patients with PHN after treatment</td>
<td align="left" valign="top">RR</td>
<td align="center" valign="top">0.11 [0.02, 0.56]</td>
<td align="center" valign="middle">0</td>
<td align="left" valign="middle">Wet cupping versus medications</td>
<td align="left" valign="middle">&#x2A01;&#x3007;&#x3007;&#x3007;Very low</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2">Yuan et al. (<xref ref-type="bibr" rid="ref34">34</xref>)</td>
<td align="left" valign="middle">Chronic neck pain</td>
<td align="center" valign="middle">2</td>
<td align="center" valign="middle">93</td>
<td align="left" valign="middle">VAS</td>
<td align="left" valign="middle">WMD</td>
<td align="center" valign="middle">&#x2212;19.0 [&#x2212;27.61, &#x2212;10.58]</td>
<td align="center" valign="middle">0</td>
<td align="left" valign="middle">Cupping vs. waitlist</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x2A01;&#x3007;Moderate</td>
</tr>
<tr>
<td align="left" valign="middle">Chronic low back pain</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">430</td>
<td align="left" valign="middle">VAS</td>
<td align="left" valign="middle">WMD</td>
<td align="center" valign="middle">&#x2212;0.54 [&#x2212;0.89, &#x2212;0.19]</td>
<td align="center" valign="middle">84.5</td>
<td align="left" valign="middle">Cupping vs. medications</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x2A01;&#x3007;Moderate</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2">Shen et al. (<xref ref-type="bibr" rid="ref29">29</xref>)</td>
<td align="left" valign="top" rowspan="2">Low Back Pain</td>
<td align="center" valign="top">3</td>
<td align="center" valign="top">146</td>
<td align="left" valign="top">VAS</td>
<td align="left" valign="top">MD</td>
<td align="center" valign="top">&#x2212;1.54 [&#x2212;1.81, &#x2212;1.26]</td>
<td align="center" valign="middle">0</td>
<td align="left" valign="middle">et cupping vs. non-cupping group</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x3007;&#x3007;Low</td>
</tr>
<tr>
<td align="center" valign="top">4</td>
<td align="center" valign="top">275</td>
<td align="left" valign="top">PPI</td>
<td align="left" valign="top">MD</td>
<td align="center" valign="top">&#x2212;2.22 [&#x2212;3.92, &#x2212;0.52]</td>
<td align="center" valign="middle">97</td>
<td align="left" valign="middle">wet cupping vs. non-cupping group</td>
<td align="left" valign="middle">&#x2A01;&#x3007;&#x3007;&#x3007;Very low</td>
</tr>
<tr>
<td align="left" valign="middle">Xie et al. (<xref ref-type="bibr" rid="ref33">33</xref>)</td>
<td align="left" valign="middle">Non-specific low back pain</td>
<td align="center" valign="middle">9</td>
<td align="center" valign="middle">736</td>
<td align="left" valign="middle">VAS</td>
<td align="left" valign="middle">MD</td>
<td align="center" valign="middle">&#x2212;1.43 [&#x2212;2.31, &#x2212;0.54]</td>
<td align="center" valign="middle">95</td>
<td align="left" valign="middle">blood pricking and cupping vs. other treatments</td>
<td align="left" valign="middle">&#x2A01;&#x2A01;&#x2A01;&#x3007;Moderate</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>AD, absolute difference; CI, confidence interval; ES, effect size; MD, mean deviation; MPPI, McGill present pain index; NPQ, Northwick Park Neck Pain Questionnaire; NRS, numerical rating scale; PHN, postherpetic neuralgia; PPI, present pain intensity; PPT, pain pressure threshold; RR, risk ratio; SMD, standard mean deviation; SMPQ, Short Form McGill Pain Questionnaire; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec20">
<label>3.5.</label>
<title>Evidence mapping</title>
<p><xref rid="fig3" ref-type="fig">Figure 3</xref> displays the outcomes of the evidence mapping, which graphically presents the evidence in the form of bubbles. The findings of the evidence mapping revealed that cupping therapy effectively alleviates pain (measured via VAS scores) for neck pain, low back pain, and knee osteoarthritis.</p>
<fig position="float" id="fig3">
<label>Figure 3</label>
<caption>
<p>Evidence mapping of cupping therapy. KOA, knee osteoarthritis; NP, neck pain; LBP, low back pain; VAS, visual analog scale. The size of the bubbles corresponds to the total population&#x2019;s sample size for the effects of cupping, with bigger bubbles representing a larger sample size. The colors symbolize the different interventions of cupping and non-cupping groups.</p>
</caption>
<graphic xlink:href="fneur-14-1266712-g003.tif"/>
</fig>
<p><xref rid="fig4" ref-type="fig">Figure 4</xref> further elucidates the evidence quality for specific pain conditions. For neck pain, there exist two moderate-quality, four low-quality, and two very low-quality evidence. There exists one low-quality evidence for chronic back pain and one very low-quality evidence for herpes zoster that demonstrates cupping therapy&#x2019;s effectiveness. Moreover, there are two moderate-quality, one low-quality, and four very low-quality evidence for low back pain, while for knee osteoarthritis, three moderate-quality evidence indicate that cupping therapy can alleviate osteoarthritis pain.</p>
<fig position="float" id="fig4">
<label>Figure 4</label>
<caption>
<p>Grade distribution of evidence of cupping therapy for pain-related conditions.</p>
</caption>
<graphic xlink:href="fneur-14-1266712-g004.tif"/>
</fig>
</sec>
</sec>
<sec sec-type="discussions" id="sec21">
<label>4.</label>
<title>Discussion</title>
<sec id="sec22">
<label>4.1.</label>
<title>Main findings</title>
<p>In the present evidence-mapping study, comprising 14 meta-analyses, the findings highlight the effectiveness of cupping therapy for various pain-related conditions. This comprehensive overview of systematic reviews summarizes the evidence on the efficacy of cupping therapy for several different pain conditions (chronic back pain, knee osteoarthritis, low back pain, neck pain, and herpes zoster). However, none of the meta-analyses provided high-quality evidence on the effectiveness of cupping therapy on pain-related outcomes. In addition, this study shows that cupping therapy is supported by moderate-quality evidence in the relief of a wide range of pain conditions, including chronic pain, knee osteoarthritis pain, low back pain, and neck pain. Some very low to low-quality evidence supports that cupping therapy for chronic back pain, low back pain, neck pain, and herpes zoster. The quality of current evidence provides good support for the clinical use of cupping therapy and direction for future cupping therapy to play a role in the treatment of other pain outcomes.</p>
</sec>
<sec id="sec23">
<label>4.2.</label>
<title>Potential mechanism of cupping therapy</title>
<p>Cupping therapy is an integral part of TCM, in which its effectiveness is increasingly recognized and substantiated by modern clinical medicine, but its physiological mechanisms have no consensus. The mechanisms of cupping therapy that have been proposed include the promotion of blood circulation, neurological reflex, the gate theory of pain, inflammation-immune reaction, and skin tension increase (<xref ref-type="bibr" rid="ref36">36</xref>).</p>
<sec id="sec24">
<label>4.2.1.</label>
<title>Neural</title>
<p>There is converging evidence that cupping therapy can induce comfort and relaxation on a systemic level, and the resulting increase in endogenous opioid production in the brain leads to improved pain control (<xref ref-type="bibr" rid="ref37">37</xref>). Furthermore, cupping therapy has been found to increase immediate pressure pain thresholds in certain areas (<xref ref-type="bibr" rid="ref38">38</xref>). In addition, the study has revealed that wet cupping therapy can decrease pain in rats <italic>via</italic> the upregulation of heat shock protein 70 (HSP70) and &#x03B2;-endorphin expression (<xref ref-type="bibr" rid="ref39">39</xref>).</p>
</sec>
<sec id="sec25">
<label>4.2.2.</label>
<title>Hematological</title>
<p>Studies have demonstrated that cupping therapy can augment blood volume and tissue oxygenation at the affected site, whereas reductions in those parameters were observed in the surrounding tissue (<xref ref-type="bibr" rid="ref40">40</xref>). Moreover, the drawing force in cupping may bring about alteration in blood flow dynamics along with the variation in dermal vascular arrangement. Cupping could positively affect erythrocyte diapedesis from superficial dermal venules. The extravasated erythrocyte may play a mediating role in the proteolytic degradation cascade of hemoglobin. The hemoglobin-derived hemorphins engage opioid receptor signaling and induce the local analgesic effect of cupping (<xref ref-type="bibr" rid="ref41">41</xref>).</p>
</sec>
<sec id="sec26">
<label>4.2.3.</label>
<title>Immune</title>
<p>A study suggests that the mechanism of cupping therapy is that cupping regulates local immunomodulation. The microenvironment is changed when stimulating the surface of the skin, and physical signals transform into biological signals, which also interact with each other in the body. These signaling cascades activate the neuroendocrine-immune system, which produces the therapeutic effect (<xref ref-type="bibr" rid="ref42">42</xref>).</p>
<p>The mechanisms of cupping therapy for pain reduction are closely related to pain gate theory, diffuse noxious inhibitory controls theory, and reflex zone theory. In summary, several theories have been proposed to explain the effects produced by cupping therapy, and these theories may overlap or alternate, producing various therapeutic effects in a specific disease (<xref ref-type="bibr" rid="ref43">43</xref>).</p>
</sec>
</sec>
<sec id="sec27">
<label>4.3.</label>
<title>Strengths and limitations</title>
<p>To sum up, our study presents the inaugural overview and evidence mapping of cupping therapy for pain-related outcomes, which comprehensively summarizes the extant evidence. The available evidence quality for the effectiveness of cupping therapy ranges from very low to moderate, with an absence of high-quality evidence. Future research endeavors should concentrate on elucidating the underlying mechanisms of cupping therapy, prioritizing avoidance of adverse events, and optimizing the design and execution of clinical investigations.</p>
<p>Unlike the protocol, our study was limited to pain-related outcomes. The rest of the methods and steps basically followed the contents of the protocol. First of all, the increase of the literature of cupping therapy for pain makes it possible to conduct an evidence mapping. Furthermore, there is consensus among authors that in registration, outcomes cover diverse diseases, but focusing on a certain area after literature screening could better reduce bias. Therefore, we proceeded with the evaluation of pain-related outcomes. We utilized stringent inclusion criteria and restricted our review to English-language literature, which may have increased the likelihood of missing relevant studies. Furthermore, we focused solely on pain-related outcomes, potentially neglecting the impact of cupping therapy on other symptoms, such as functional activities. It is worth noting that non-specific and chronic neck pain were included in our analysis under the umbrella term &#x201C;neck pain,&#x201D; while non-specific and chronic low back pain were considered collectively as &#x201C;low back pain.&#x201D; Nonetheless, it is essential for better-quality research to validate the current evidence.</p>
</sec>
</sec>
<sec sec-type="conclusions" id="sec28">
<label>5.</label>
<title>Conclusion</title>
<p>Cupping therapy appears to be a promising treatment modality for various pain-related disorders. It is effective in the treatment of chronic pain, knee osteoarthritis, low back pain, neck pain, chronic back pain, and herpes zoster. However, the quality of the evidence supporting these outcomes is mostly low quality, with moderate-quality evidence still less available and no high-quality. Therefore, to strengthen these findings, more high-quality clinical studies are also needed to obtain a higher level of evidence. Nonetheless, the potential benefits of cupping therapy in clinical practice make it a valuable intervention for further research and implementation.</p>
</sec>
<sec sec-type="data-availability" id="sec29">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/<xref ref-type="supplementary-material" rid="SM1">Supplementary material</xref>, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec sec-type="author-contributions" id="sec30">
<title>Author contributions</title>
<p>LW: Software, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing, Conceptualization, Data curation, Formal analysis, Investigation, Methodology. ZC: Data curation, Formal analysis, Investigation, Methodology, Software, Writing &#x2013; review &#x0026; editing. XL: Data curation, Formal analysis, Investigation, Methodology, Software, Writing &#x2013; review &#x0026; editing. AZ: Conceptualization, Investigation, Supervision, Writing &#x2013; review &#x0026; editing.</p>
</sec>
</body>
<back>
<sec sec-type="funding-information" id="sec31">
<title>Funding</title>
<p>The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was funded by the National Key R&#x0026;D Program of the Ministry of Science and Technology of China Key Special Program for &#x201C;Modernization Research of Traditional Chinese Medicine&#x201D; (grant number 2019YFC1708701) and Zhejiang Chinese Medical University&#x2019;s 2022 School-level Scientific Research Project Talent Project (grant number 2022RCZXZK19).</p>
</sec>
<sec sec-type="COI-statement" id="sec32">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="sec100" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="sec33">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fneur.2023.1266712/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fneur.2023.1266712/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Table_1.DOCX" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
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