Skip to main content
PLOS One logoLink to PLOS One
. 2023 Sep 28;18(9):e0291053. doi: 10.1371/journal.pone.0291053

The effect of nature exposure on pain experience and quality of life in patients with chronic pain: A systematic review and meta-analysis protocol

Matthew J Lee 1,*, Aishwarya Pradeep 2, Katie Lobner 3, Oluwakemi Badaki-Makun 4,*
Editor: Germain Honvo5
PMCID: PMC10538778  PMID: 37768931

Abstract

Background

Chronic pain is a complex condition with short and long-term effects on physical and psychosocial health. Nature exposure therapy has been investigated as a potential non-pharmacological intervention to improve physical and emotional health of individuals with chronic pain. This proposed systematic review aims to examine the effects of nature exposure therapy on pain experience and quality of life in patients with chronic pain.

Methods

Studies will be identified by searching the MEDLINE, Embase and Cumulative Index for Nursing and Allied Health Literature (CINAHL) databases. All included studies will be required to be interventional controlled trials comparing nature exposure therapy to placebo or standard care in patients with chronic pain. Primary outcomes for this review will be pain intensity and quality of life scores. Secondary outcomes will include self-efficacy, depression and pain-related anxiety scores. If 2 or more studies are included, results will be pooled for meta-analysis. If meta-analysis is not possible, the results will be presented in a narrative form.

Discussion

Given the adverse effects of opioid use, non-pharmacological interventions are a necessary alternative to treat patients with chronic pain. Nature exposure therapy is an intriguing example of such an intervention. We hope that this systematic review will guide future clinical decision-making for patients with chronic pain and provide evidence for or against the need for natural spaces and improved urban planning.

Trial registration

PROSPERO registration number: CRD42021226949.

Introduction

Chronic pain remains a complex public health issue with emotional, physical and socioeconomic implications [13]. According to the Centers for Disease Control and Prevention (CDC), approximately 20.4% of adults in the U.S experienced some form of chronic pain in 2019 and 7.4% reported it interfering with work and daily life activities [4]. While most attention is directed towards the adult population, a significant number of children develop chronic pain as well [5]. It is estimated that approximately 8% of children experience chronic pain worldwide [6]. For the purposes of this review, we will draw upon the International Association for the Study of Pain’s (IASP) definition of pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage.” We will also use the ICD-11 definition of chronic pain as pain which has “persisted beyond normal healing time and has recurred for more than 3 months.” Both primary chronic pain (i.e., headache pain, widespread pain, etc.) and chronic pain secondary to underlying disease (i.e., cancer-related pain, post-surgical pain, visceral pain) will be considered for this review.

Chronic pain can stem from several causes. Often it is the sequelae of persistent and recurring pain from chronic conditions, neuropathy or musculoskeletal causes such as joint pain [7]. Chronic pain can also be a potential long-term complication of surgical procedures. Although dependent on the type of operation, postsurgical chronic pain is estimated to affect up to 50% of adults following surgery [8].

Opioids have long been a popular treatment option in the management of patients with chronic pain [9]. However, given their addictive effects and high rates of opioid overdose deaths, non-pharmacological interventions have been examined as potential alternatives [10]. Nature exposure therapy is an example of such an intervention that may be useful in chronic pain rehabilitation.

Nature is defined as the animals, flora, landscape or natural products of the Earth that an individual can perceive or interact with through their senses. Exposure to nature has been linked to improvements in several health outcomes including pain intensity and anxiety [1113]. While the mechanisms are still unclear, it has been hypothesized that green light from natural sceneries may induce positive emotions and subsequently alleviate pain and pain-associated psychological symptoms [14]. Through exposure to natural settings, nature exposure therapy utilizes these therapeutic effects of nature in the treatment of medical and psychiatric conditions.

Given the advancement of technology in recent years, nature exposure therapy may also integrate virtual components [15]. Virtual reality programs using natural scenery (e.g., forest, grasslands, ocean) and nature sounds have been used in medical rehabilitation and have demonstrated improvements in depression, stress and pain [16, 17]. With the lack of green spaces in certain urban communities, such interventions may be effective alternatives [18].

While the literature indicates that nature exposure therapy can have therapeutic effects, little is known about its impact in those with chronic pain. To date, there are no high-quality systematic reviews examining the effects of nature exposure therapy in patients with chronic pain. Thus, it is vital that this review investigates the literature and evaluates the potential benefits of this non-pharmacological intervention. This proposed systematic review aims to examine the effects of nature exposure therapy on pain experience and quality of life in patients with chronic pain.

Methods

In conducting this systematic review, we will follow the methodology outlined in the Cochrane Handbook for Systematic Reviews of Interventions. This systematic review protocol is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA-P) guide (S1 Appendix) [19] and has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021226949). Upon completion, this systematic review will be reported in alignment with the PRISMA 2020 statement.

Eligibility criteria

Controlled studies comparing nature exposure therapy to placebo or standard care in the treatment of patients with chronic pain will be included this study. We will consider studies with participants of all ages experiencing any primary or secondary chronic pain. Studies with interventions using physical or virtual nature exposure therapies to alleviate pain in either the inpatient or outpatient clinical environment will be included. Given the breadth of nature exposure, all ecosystems (e.g., greenspace, blue space) will be considered for this review. No limitations will be imposed on the form of nature exposure intervention, which can encompass both passive (e.g., observing nature) and active (e.g., participating in nature-based activities) experiences. The comparator group in this systematic review will be patients receiving placebo or standard pharmacological or non-pharmacological treatments for pain such as analgesics and physical therapy. There will be no restrictions placed on the year of publication and country of origin.

Trials using nature exposure therapies as secondary treatments or interventions involving the pharmacological use or consumption of medicinal plants, herbs and other flora will be excluded from this review. Trials using combination therapy of pharmacological analgesics and nature exposure as a primary intervention will also be excluded. Studies using subjective measures of pain as primary or secondary outcomes will not be considered for this review. Studies written in languages other than English will be excluded.

Information sources and search strategy

To identify relevant studies, we will conduct a search of the MEDLINE, Embase, and Cumulative Index for Nursing and Allied Health Literature (CINAHL) databases. Our search strategies will utilize a combination of terms derived from the PICOS framework, as outlined in S1 Table and S2 Appendix.

Selection of studies

Two review authors (MJL and AP) will first independently screen for study eligibility by reading the titles and abstracts. Studies inconsistent with the eligibility criteria will be excluded. Disagreements concerning study inclusion will be resolved through decision from a third author (OBM). Following title and abstract assessment, two independent authors (MJL and AP) will review the full text of the remaining eligible studies. Conflicts will be resolved by a third author (OBM). A PRISMA flow chart will be included in order to display the screening process.

Data extraction and management

Two review authors (MJL and AP) will independently extract data using Covidence prior to entering information into Review Manager 5.4 (RevMan5.4). A third author (OBM) will adjudicate in case of disagreement. We will extract the following information:

  • Bibliographic data (authors, years, date of publication)

  • Methods: aims of study, study design, method of recruitment, declaration of interests of investigators

  • Characteristics of participants (age, gender, condition, duration of pain, treatment)

  • Description of nature intervention (virtual vs. physical, specific ecosystem, interactive vs. passive experience, duration of nature exposure)

  • Description of control group intervention (pharmacological vs. non-pharmacological)

  • Outcomes of Interest: (pain, quality of life and psychosocial outcomes)

Outcome measures

Primary outcomes

Reduction in pain intensity will be a primary outcome. We will examine quantitative pain intensity scores and self-report measures such as the Visual Analog Scale (VAS) and the numerical rating pain scale. Quality of life will also be a primary outcome that will be assessed. Quantitative measures such as the Quality-of-Life Scale (QLOS) and the 36-item short form survey (SF-36) will be used along with other measures.

Secondary outcomes

Psychosocial outcomes will also be measured. Self-efficacy, depression and pain-related anxiety scores are secondary outcomes that will be assessed through this systematic review.

Assessment of risk of bias in included studies

Two authors (MJL and AP) will independently assess the risk in accordance with the Cochrane bias risk tool [20]. We will assess the following items: blinding (participants, personnel, and outcome assessors); sequence generation; incomplete outcome data; and other potential threats to validity. We will assess the studies and judge each as: low risk, high risk or unclear risk of bias. We will make necessary judgements and a third author (OBM) will adjudicate in case of any disagreements.

Data analysis and synthesis

Our decision to meta-analyze study data will be dependent on the number of included studies (2 or more) and whether trials are similar in terms of participants, settings, intervention, comparison and outcome measures. If meta-analysis is conducted, studies will be pooled using the RevMan5.4 software, utilizing the inverse variance method. We aim to apply a random-effect model as we anticipate our outcome measures to assess the same underlying intervention effect.

In order to account for differing outcome measurements across included studies, effect sizes will be presented using the standardized mean difference (SMD) with corresponding 95% confidence intervals. We anticipate that outcomes will be continuous and plan to evaluate differences in pre- and post-intervention values or absolute post-intervention values. Skewness of outcome data will be assessed using statistical methods. If substantial skewness is identified, it will be considered in our analysis and interpretation of results.

We will utilize the I2 statistic to determine the extent to which variation across the included studies is due to heterogeneity compared to chance. We will interpret the percent ranges as follows: 0% to 40% suggests insignificant heterogeneity, 30% to 60% suggests moderate heterogeneity, 50% to 90% suggests substantial heterogeneity, 75% to 100% suggests considerable heterogeneity.

Subgroup analyses will be conducted if there is sufficient data available to compare different forms of nature exposure interventions (e.g., interactive vs. passive experience, physical vs. virtual, different ecosystems), as well as the duration of the nature exposure intervention and the duration of follow-up. If the review yields other significant findings, additional subgroup analyses may be carried out.

Sensitivity analysis will be conducted to evaluate the impact of excluding studies with high risk of bias. We will also use the Egger test and construct funnel plots to visually present the effect sizes and determine the presence of publication bias [21]. If meta-analysis is not possible, the results from the included studies will be presented in a narrative manner and findings within and between trials will be described and presented through figures and tables.

Assessing the certainty of evidence

We will adhere to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach when evaluating the certainty of evidence. We will use the following criteria:

  • High: very confident that true effect is close to estimated effect

  • Moderate: moderately confident in estimated effect and true effect is likely close to that but may be different

  • Low: confident in estimated effect is limited

  • Very low: very little confidence in estimated effect

We will then create a “Summary of Findings” table using the GRADEpro software [22] and use the GRADE system to evaluate the evidence.

Discussion

This systematic review aims to identify the comprehensive impacts of nature exposure therapy in patients experiencing chronic pain. While pain intensity is often the primary area of concern in patients with this condition, individual quality of life and psychosocial health are often affected as well. The literature suggests that the therapeutic effects of nature exposure therapy may improve these outcomes, making it an intriguing intervention in the rehabilitation of chronic pain. The results of this review will summarize the evidence and determine whether nature exposure therapy can have beneficial effects in patients with this condition.

To our knowledge, no systematic review currently exists that examines the effects of nature exposure therapy in patients with chronic pain. There is also a lack of universally recognized standards accessible to physicians for prescribing nature exposure as a means of treating chronic pain. We hope this review will serve as a significant resource to clinicians by providing objective evidence on a potential non-pharmacological alternative to opioids and other analgesics. Due to the wide range of nature exposure therapies, we aim to offer recommendations on effective types and durations of interventions for individuals with chronic pain. We believe our review will highlight the importance of conducting more high-quality randomized controlled trials on nature exposure therapy and increasing the availability of natural spaces in urban areas to support the management of chronic pain.

Supporting information

S1 Table. Search strategy.

(TIFF)

S1 Appendix. PRISMA-P checklist.

(DOC)

S2 Appendix. Search strategy.

(DOCX)

Data Availability

No datasets were generated or analysed during the current study. Data extraction files from this study will be made available upon study completion.

Funding Statement

The authors received no specific funding for this work.

References

  • 1.Yong RJ, Mullins PM, Bhattacharyya N. Prevalence of chronic pain among adults in the United States. Pain. 2022. Feb;163(2):e328–32. doi: 10.1097/j.pain.0000000000002291 [DOI] [PubMed] [Google Scholar]
  • 2.Clauw DJ, Essex MN, Pitman V, Jones KD. Reframing chronic pain as a disease, not a symptom: rationale and implications for pain management. Postgraduate Medicine. 2019. Apr 3;131(3):185–98. doi: 10.1080/00325481.2019.1574403 [DOI] [PubMed] [Google Scholar]
  • 3.Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, et al. Chronic pain as a symptom or a disease: the IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11). Pain. 2019. Jan;160(1):19–27. doi: 10.1097/j.pain.0000000000001384 [DOI] [PubMed] [Google Scholar]
  • 4.Zelaya CE, Dahlhamer JM, Lucas JW, Connor EM. Chronic Pain and High-impact Chronic Pain Among U.S. Adults, 2019. NCHS data brief, no. 390. Hyattsville, MD: National Center for Health Statistics. 2020. [PubMed] [Google Scholar]
  • 5.Friedrichsdorf S, Giordano J, Desai Dakoji K, Warmuth A, Daughtry C, Schulz C. Chronic pain in children and adolescents: Diagnosis and treatment of primary pain disorders in head, abdomen, muscles and joints. Children. 2016;3(4):42. doi: 10.3390/children3040042 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Liao ZW, Le C, Kynes JM, Niconchuk JA, Pinto E, Laferriere HE, et al. Paediatric chronic pain prevalence in low- and middle-income countries: A systematic review and meta-analysis. eClinicalMedicine. 2022. Mar;45:101296. doi: 10.1016/j.eclinm.2022.101296 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Mathews L. Pain in children: Neglected, unaddressed and mismanaged. Indian Journal of Palliative Care. 2011;17(4):70. doi: 10.4103/0973-1075.76247 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Papadomanolakis-Pakis N, Uhrbrand P, Haroutounian S, Nikolajsen L. Prognostic prediction models for chronic postsurgical pain in adults: a systematic review. Pain. 2021. Nov;162(11):2644–57. doi: 10.1097/j.pain.0000000000002261 [DOI] [PubMed] [Google Scholar]
  • 9.Dassieu L, Kaboré JL, Choinière M, Arruda N, Roy É. Chronic pain management among people who use drugs: A health policy challenge in the context of the opioid crisis. International Journal of Drug Policy. 2019. Sep;71:150–6. doi: 10.1016/j.drugpo.2019.03.023 [DOI] [PubMed] [Google Scholar]
  • 10.Kligler B, Bair MJ, Banerjea R, DeBar L, Ezeji-Okoye S, Lisi A, et al. Clinical Policy Recommendations from the VHA State-of-the-Art Conference on Non-Pharmacological Approaches to Chronic Musculoskeletal Pain. J GEN INTERN MED. 2018. May;33(S1):16–23. doi: 10.1007/s11606-018-4323-z [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Fuller RA, Irvine KN, Devine-Wright P, Warren PH, Gaston KJ. Psychological benefits of greenspace increase with biodiversity. Biology Letters. 2007;3(4):390–4. doi: 10.1098/rsbl.2007.0149 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Repke MA, Berry MS, Conway LG, Metcalf A, Hensen RM, Phelan C. How does nature exposure make people healthier?: Evidence for the role of impulsivity and expanded space perception. Colarelli SM, editor. PLoS ONE. 2018. Aug 22;13(8):e0202246. doi: 10.1371/journal.pone.0202246 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Jimenez MP, DeVille NV, Elliott EG, Schiff JE, Wilt GE, Hart JE, et al. Associations between Nature Exposure and Health: A Review of the Evidence. IJERPH. 2021. Apr 30;18(9):4790. doi: 10.3390/ijerph18094790 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Berry MS, Rung JM, Crawford MC, Yurasek AM, Ferreiro AV, Almog S. Using greenspace and nature exposure as an adjunctive treatment for opioid and substance use disorders: Preliminary evidence and potential mechanisms. Behavioural Processes. 2021. May;186:104344. doi: 10.1016/j.beproc.2021.104344 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Li H, Zhang X, Wang H, Yang Z, Liu H, Cao Y, et al. Access to Nature via Virtual Reality: A Mini-Review. Front Psychol. 2021. Oct 5;12:725288. doi: 10.3389/fpsyg.2021.725288 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Mostajeran F, Krzikawski J, Steinicke F, Kühn S. Effects of exposure to immersive videos and photo slideshows of forest and urban environments. Sci Rep. 2021. Dec;11(1):3994. doi: 10.1038/s41598-021-83277-y [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.White MP, Yeo N, Vassiljev P, Lundstedt R, Wallergård M, Albin M, et al. A prescription for “nature”—The potential of using virtual nature in therapeutics. NDT. 2018. Nov;Volume 14:3001–13. doi: 10.2147/NDT.S179038 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Yu CP, Lee HY, Luo XY. The effect of virtual reality forest and urban environments on physiological and psychological responses. Urban Forestry & Urban Greening. 2018. Oct;35:106–14. [Google Scholar]
  • 19.Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al., PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;349:g7647. doi: 10.1136/bmj.g7647 . [DOI] [PubMed] [Google Scholar]
  • 20.Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane database of systematic reviews. 2019; 10:Ed000142. Epub 2019/10/24. doi: 10.1002/14651858.ED000142 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. Grade: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6. doi: 10.1136/bmj.39489.470347.AD [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.GRADEpro. https://gradepro.org/.

Decision Letter 0

Germain Honvo

15 Nov 2022

PONE-D-22-27571The Effect of Nature Exposure on Pain Experience and Quality of Life in Patients with Chronic Pain: A Systematic Review and Meta-Analysis ProtocolPLOS ONE

Dear Dr. Lee,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Dec 30 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Germain Honvo, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We note that this manuscript is a systematic review or meta-analysis; our author guidelines therefore require that you use PRISMA guidance to help improve reporting quality of this type of study. Please upload copies of the completed PRISMA checklist as Supporting Information with a file name “PRISMA checklist”.

Additional Editor Comments:

There are some important methodological flaws in this protocol, which make it not acceptable for publication in its current form. Here are some specific issues that need to be addressed.

1. Please note that there is a difference between methodology guidelines and reporting guidelines. The PRISMA-P is rather a reporting guideline. The authors should refer to adequate methodology guidelines for the conduct of this systematic review (in this particular case, the guidelines in the Cochrane handbook may be appropriate), then to the PRISMA-P as a reporting guideline for this protocol manuscript. Therefore, the sentence “This systematic review protocol is designed in accordance with the guidelines provided in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statement” should be amended.

2. Please note that exclusion criteria are not opposite of inclusion criteria. Therefore, the following should be removed from the manuscript: “Case control, proof-of-concept, two-gate studies and case studies will be excluded”; since this systematic review is on interventional controlled trials.

3. The authors need to provide adequate and detailed search strategy for at least one of the databases considered for this systematic review. This should be provided as a supplementary file.

4. The authors declared that “The search strategy will be composed of four concepts combined with Boolean operators: “nature,” “chronic pain,” “treatment,” and “controlled trials.” Considering the PICOS framework and the research question in this systematic review, the ‘concept’ “treatment” does not seem to be the most adequate in the search strategy to denote the ‘outcome’.

5. The Editor does not see the added value of a blank flow-chart in a protocol manuscript, though this practice has been sometimes seen in the literature. Please consider removing this.

6. Instead of presenting the following subtitles in the methods section (i.e., ‘Types of Studies’, ‘Types of Participants ‘, ‘Types of Intervention’) and in accordance with the PRISMA-P checklist, the Editor advises the authors to report the ‘Eligibility criteria’, as a clear section, with one paragraph on inclusion criteria, and another one on exclusion criteria. Please consider being concise. Then, another separate section on ‘Outcomes and prioritization’ should be reported.

7. The following should be removed from the data extraction section: “Risk of bias: specified under Assessment of risk bias in included studies”. This is not a data to extract.

8. For the structure of the methods section, please consider strictly following the PRISMA-P. This will ease reading and understanding for potential future readers of this manuscript.

9. For risk of bias assessment, instead of stating “… will independently assess the risk in accordance with the Cochrane Handbook for Systematic Reviews of Interventions”, please state that the Cochrane risk of bias tool will be used (not the handbook).

10. In accordance with the PRISMA-P, please remove the GRADE assessment from the data analysis section. These are indeed two different things.

11. The Data synthesis section is very poorly described. Please refer to previous well reported meta-analyses and to the Cochrane handbook for systematic reviews for guidance. The statistical analyses planned should be clearly reported in this section, with assumptions guiding the choices made.

12. Please remove the section on “Measures of treatment effect” from the manuscript and move relevant information to the data analysis section. Please note that the following sentence in this section does not make any sense: “To test the significance of the RR and 95% CI, we will use the chi squared test”.

13. What is the meaning of this sentence in a meta-analysis where the authors are planning the calculate SMDs: “T-tests and ANOVA tests will be utilized when comparing two means and multiple mean values respectively”?

14. The Editor advises the authors to take the necessary time to adequately revise this manuscript before resubmitting it to the Journal. If the authors feel it necessary, the Editor advises them to ask for the help of colleagues with strong experience in the conduct of systematic reviews and meta-analyses, to improve this protocol (indeed, the Editor thinks this may be necessary).

Thank you.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: No

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: No

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #1: 

This review and meta-analysis will examine the effects of nature exposure (both actual and visual) on pain and quality of life measures among individuals with chronic pain. This review is timely and will be of interest to the readers from various disciplines. Given the high percentage of pain conditions in the general population, as well as the detrimental effects of common pain care approaches (e.g., opioid prescriptions), it is critical to develop non-pharmacological options for patients with pain and anxiety about their pain. I suggest consideration of the following minor points to strengthen the methods of this review and meta-analysis:

• “Greenspace” should be added to search terms in addition to just “nature,” especially given greenspace and the color green may have explicit pain reducing properties (perhaps more so than other types of nature, however that remains to be seen).

• While this may be the intentions of the authors already, it would help to explicitly state in the data extraction more overt details in addition to “type” of nature. Does this mean virtual or actual nature exposure? Or does this mean various nature ecosystems such as greenspace versus bluespace or others? There are also active versus passive experiences with nature, does this matter? How much time of exposure would also be very helpful, as there may be a minimum threshold. Just a few more explicit details on what the authors intend to collect would be very helpful. A couple of these thoughts came to the fore in the discussion, however should be listed explicitly in the methods.

• The above point will be a critical component of the discussion of this review. The implications being that perhaps some nature exposure might be beneficial, but there might be a minimum threshold that is needed to reach that point (e.g., minutes spent viewing nature, “quality” of nature viewed). From this exciting review, I hope that the authors are able to glean specific recommendations moving forward for both future research and practice. However if the actual intervention of nature (i.e., the independent variable in this case), is not documented extensively, the review may fall short of this.

• May also be worth noting that nature prescriptions from physicians are gaining traction in several countries, but specific guidelines for these prescriptions for any conditions (including pain) are not well fleshed out, and this review will be a critical step in synthesizing the research to reach “prescription guidelines.”

Reviewer #2: 

In general, the protocol regarding a systematic review and meta-analysis of the effect of nature exposure on pain experience and quality of life in patients with chronic pain was well written. However, no control or comparison was described in the PICO framework. Besides, inclusion and exclusion criteria of the articles were not described in detail.

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Decision Letter 1

Germain Honvo

16 Jun 2023

PONE-D-22-27571R1The Effect of Nature Exposure on Pain Experience and Quality of Life in Patients with Chronic Pain: A Systematic Review and Meta-Analysis ProtocolPLOS ONE

Dear Dr. Lee,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jul 31 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Germain Honvo, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Thank you to the authors for their revisions, which have significantly improved this systematic review protocol. Please consider some few (important) additional comments to further improve this protocol.

1) Abstract: Please remove the following from the abstract, as per a previous Editor’s comment: “Case control, proof-of-concept, two-gate studies and case studies will be excluded” (lines 32-33).

2) Introduction to the methods section: Please consider reporting first which methodology guideline will be followed to conduct this systematic review before stating which one was followed to report the current protocol. Please refer to the Editor’s previous comment n°1 (first peer review round). In addition to these two guidelines, please also add that once completed, this systematic review will be reported according to the PRISMA 2020 statement.

3) Eligibility criteria: Please move the exclusion criterion “Studies written in languages other than English will be excluded” to the end of the list of exclusion criteria, as this is not the most important one in this study.

4) Section on “Search strategy”: Please remove the sentence starting by “To ensure consistency and collaboration between…” (lines 120-122), as this has nothing to do with search strategies.

5) Please consider providing the search strategies as a supplementary MS Word document. Second, as Medline and Embase do not use the same thesaurus, please note that it is necessary to provide search strategies tailored to each database separately (including CINAHL). Please note that the validity of systematic reviews primarily depends on the quality of search strategies.

6) Selection of studies: Please change “Studies inconsistent with the inclusion criteria will be excluded” to “Studies inconsistent with the eligibility criteria will be excluded”. Please note that both inclusion and exclusion criteria are always considered for studies selection (including title/abstract selection). The last but one sentence (lines 129-131) is not very clear. Please rephrase or delete; then add that full text selection will follow title/abstract selection.

7) Data analysis: For effect sizes calculations, anticipating that different outcome measurements may have been used, please consider using SMDs only (not MD and SMD). This will ease comparisons of treatment effects.

Please note that subgroup analysis is heterogeneity assessment.

Please remove “If >10 studies are included in meta-analysis, we will assess for heterogeneity”.

Please refer to the Cochrane handbook and to high quality systematic reviews for guidance to improve this section. Thank you for your understanding.

8) Please consider changing the title ‘Assessing certainty in findings’ to ‘Assessing the certainly of evidence’.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: I can confirm that my previous comments have been adequately addressed. I have no further comments at this time. Thank you.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Decision Letter 2

Germain Honvo

22 Aug 2023

The Effect of Nature Exposure on Pain Experience and Quality of Life in Patients with Chronic Pain: A Systematic Review and Meta-Analysis Protocol

PONE-D-22-27571R2

Dear Dr. Lee,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Germain Honvo, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Final minor comments:

Thank you for addressing all the previous comments. Please make these few additional changes before publication of your protocol.

- Methods section: Please change the title « Search strategy » to « Information sources and Search strategy”, to best fit with the content of this section.

- In the data analysis section, are you mentioning “histograms” or “funnel plot”? Please consider revising this before publication of the protocol. Please refer to well reported systematic reviews and meta-analyses. Thank you.

- The Editor suggests applying a random-effects model, instead of a fixed-effect model (considering what you stated in the rest of the data-analysis section). Therefore, the last sentence of the first paragraph of the “Data analysis and synthesis” should be rephrased. Please consider revising this before publication of the protocol. Thank you.

Reviewers' comments:

Acceptance letter

Germain Honvo

19 Sep 2023

PONE-D-22-27571R2

The Effect of Nature Exposure on Pain Experience and Quality of Life in Patients with Chronic Pain: A Systematic Review and Meta-Analysis Protocol

Dear Dr. Lee:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Germain Honvo

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Search strategy.

    (TIFF)

    S1 Appendix. PRISMA-P checklist.

    (DOC)

    S2 Appendix. Search strategy.

    (DOCX)

    Attachment

    Submitted filename: Response to Reviewers.pdf

    Attachment

    Submitted filename: Response to Reviewers V2.pdf

    Data Availability Statement

    No datasets were generated or analysed during the current study. Data extraction files from this study will be made available upon study completion.


    Articles from PLOS ONE are provided here courtesy of PLOS

    RESOURCES