{"paper_id":"6a455e64-b7e2-4adf-b05d-400d04d6612a","body_text":"LETTER\nA Response to: Letter to the Editor Regarding\n‘‘Gabapentin has Longer-Term Efficacy\nfor the Treatment of Chronic Pelvic Pain in Women:\nA Systematic Review and Pilot Meta-analysis’’\nYi-Feng Ren . Xiu-Mei Fan . Xi Fu . Hao Wu . Xin Ye .\nYi-Fang Jiang . Feng-Ming You\nReceived: November 18, 2021 / Accepted: December 21, 2021 / Published online: January 19, 2022\n/C211The Author(s) 2022\nKeywords: Chronic pelvic pain; Gabapentin;\nLonger-term benefits Key Summary Points\nAlthough several clinical studies have\nevaluated gabapentin for the treatment of\nchronic pelvic pain in women, efficacy\nand safety of this therapy remains\ncontroversial.\nThe published meta-analysis evaluated\nefficacy and safety of gabapentin for\ntreatment of chronic pelvic pain in\nwomen, and the results revealed that\ngabapentin has potential analgesic effects\nin this group of patients.\nThis is a response article to: Letter to the\nEditor regarding ‘ ‘Gabapentin has Longer-\nTerm Efficacy for the Treatment of\nChronic Pelvic Pain in Women: A\nSystematic Review and Pilot Meta-\nanalysis’ ’.\nDear Editor,\nThank you for informing us about the letter\ndiscussing the results of ‘ ‘Gabapentin has\nLonger-Term Efficacy for the Treatment of\nChronic Pelvic Pain in Women: A Systematic\nReview and Pilot Meta-analysis’ ’ [1]. Meanwhile,\nYi-Feng Ren and Xiu-Mei Fan contributed equally to this\nwork as co-first authors.\nY.-F. Ren /C1X.-M. Fan /C1X. Fu /C1H. Wu /C1X. Ye /C1\nY.-F. Jiang ( &) /C1F.-M. You ( &)\nHospital of Chengdu University of Traditional\nChinese Medicine, Chengdu 610072, Sichuan\nProvince, China\ne-mail: jyftcm@163.comF.-M. You\ne-mail: yfmdoc@163.com\nY.-F. Jiang /C1F.-M. You\nTCM Regulating Metabolic Diseases Key Laboratory\nof Sichuan Province, Hospital of Chengdu\nUniversity of Traditional Chinese Medicine,\nChengdu 610072, Sichuan Province, China\nPain Ther (2022) 11:321–325\nhttps://doi.org/10.1007/s40122-021-00352-y\n\nTable 1 Additional analysis of primary outcomes\nOutcome Studies\nincluded\nGabapentin,\nmean (SD)\nControl,\nmean (SD)\nWMD (95% CI) P value for\nstatistical\nsignificance\nP value for\nheterogeneity\nI\n2 test for\nheterogeneity\n(%)\nQuality of\nevidence\n(GRADE)\nPrimary outcomes (including the trial of Horne et al.)\nThe change in pain\nscores from baseline\nduring the first\n3 months of treatment\n4 - 1.60 (4.04) - 1.25 (4.09) - 0.61 ( - 0.97 to - 0.25) 0.0009 0.82 0 /C8/C8/C8 /C13\nModerate\nThe change in pain\nscores from baseline\nduring the first\n6 months of treatment\n4 - 2.01 (2.43) - 1.37 (2.26) - 1.00 ( - 1.69, - 0.30) 0.0005 0.03 66 /C8/C8 /C8 /C13\nModerate\nPrimary outcomes (excluding the trial of Horne et al.)\nThe change in pain\nscores from baseline\nduring the first\n3 months of treatment\n3 - 2.75 (2.58) - 2.12 (2.65) - 0.66 ( - 1.04, - 0.28) 0.0007 0.85 0 /C8/C8/C8/C13\nModerate\nThe change in pain\nscores from baseline\nduring the first\n6 months of treatment\n3 - 3.87 (2.31) - 2.87 (2.63) - 1.38 ( - 1.89 to - 0.88) \\ 0.00001 0.55 0 /C8/C8/C8/C13\nModerate\n322 Pain Ther (2022) 11:321–325\n\nwe also appreciate the comments by Vincent\net al. about our research.\nIn relation to their first comment, we cer-\ntainly agree that Vincent et al. conducted a\nhigh-quality study about the efficacy and safety\nof gabapentin treatment for chronic pelvic pain\n(CPP) in women [ 2]. Their outcome variables\nwere assessed during 13 to 16 weeks, which\nwere far shorter than 6 months (24 weeks).\nTherefore, this outcome was not included in our\npilot meta-analysis of ‘the change in pain scores\nfrom the baseline during the first 6 months\ntreatment’. However, in order to eliminate\npotential misunderstanding, we did an addi-\ntional analysis of data of Horne et al. in this\nresponse article. The results showed that neither\nincluding nor excluding the trial of Horne et al.\nhad a significant alteration for the primary\noutcomes (see Table 1). Besides, it is noteworthy\nthat our results [ 1] are consistent with those\nfrom Lewis et al., 2016, which conducted by\ntheir team [ 3]. Similarly, Putzke and colleagues\nalso found that gabapentin had a longer-term\nanalgesic effect (3 years) for pain after traumatic\nspinal cord injury [ 4]. Finally, Biggs et al.\ndemonstrated that gabapentin exerted long-\nterm effects on pain relief from the angle of\nanimal experiments [ 5]. Therefore, there are\ncurrently potential clinical, experimental, and\nstatistical evidence about the long-term effects\nin the gabapentin treatment for CPP in women,\nand it is necessary and meaningful to design\nmore high-quality studies for further\nclarification.\nSecond, regarding ‘the use of change in pain\nscores’ as an indicator to evaluate the degree of\npain improvement, we consider it is reasonable.\nThere are some reasons: (i) In the present anal-\nysis, the change in pain scores was calculated as\npain score at 3 months or 6 months minus\nbaseline pain scores. Thus, it had already been\ntaken into account of baseline pain severity,\nand could further strengthen the external\nvalidity. (ii) The change in pain score was the\nmost frequently reported outcome in all inclu-\nded studies. (iii) There have been a number of\npast high-quality studies using ‘ ‘the change in\npain scores’ ’ as the primary outcome measures\n[6–8]. (iv) We applied the minimally clinically\nimportant difference (MCID) to interpret results\non the change in pain scores from baseline to\n3 months and 6 months. Likewise, when for-\nmulating the MCID, the effect of baseline pain\nwas considered [ 9].\nThird, we agree with Vincent et al. that there\nis a risk of gabapentin-related adverse events in\nthe treatment of CPP in women. As such, we\nalso suggested that ‘patients with major neuro-\nlogic conditions are advised to avoid gaba-\npentin-based treatment’ in the discussion\nsection of the paper [ 1]. Additionally, Horowitz\net al. also showed that further studies were\nneeded to assess the long-term efficacy and\nsafety of gabapentin for patients with anxiety\nand other mental health conditions [ 10]. In\nfact, although there were some adverse events,\nour results showed that gabapentin was also an\neffective treatment option for patients with CPP\n[1]. Of note, more recently, epidemiological\nstudies confirmed that the gabapentinoids\nappeared to possess no addictive potential\nthemselves, and even had a positive benefit in\nclinical therapeutics [ 11].\nFinally, we also agree that it is very hard to\ndraw a solid conclusion on the basis of such a\nsmall sample size. We also acknowledge that the\npossibility of small sample effect cannot be fully\nruled out, despite the homogeneity of data\ndilutes this possibility. Therefore, the finding of\nthis pilot meta-analysis needs to be considered\nexploratory and interpreted with caution, and\nthe high-quality studies are needed to verify the\nefficacy of gabapentin treatment for CPP in\nwomen.\nWe deeply thank Vincent et al. and col-\nleagues again for their contribution to this dis-\ncussion and would welcome any other criticism.\nACKNOWLEDGEMENTS\nFunding. No funding or sponsorship was\nreceived for this study or publication of this\nletter.\nAuthorship. All named authors meet the\nInternational Committee of Medical Journal\nEditors (ICMJE) criteria for authorship for this\narticle, take responsibility for the integrity of\nPain Ther (2022) 11:321–325 323\n\nthe work as a whole, and have given their\napproval for this version to be published.\nAuthor Contributions. Yi-Feng Ren: Statis-\ntical Analysis, Writing-original draft, Valida-\ntion. Xiu-Mei Fan: Writing-original draft,\nValidation. Xi Fu: Data collection, Methodol-\nogy, Writing-original draft, Validation. Hao\nWu: Data collection, Methodology, Validation.\nXin Ye: Data collection, Validation. Yi-Fang\nJiang: Conceptualization, Writing-review &\nediting, Validation. Feng-Ming You: Conceptu-\nalization, Methodology, Writing-review & edit-\ning, Validation.\nDisclosures. Yi-Feng Ren, Xiu-Mei Fan, Xi\nFu, Hao Wu, Xin Ye, Yi-Fang Jiang, and Feng-\nMing You have nothing to disclose.\nCompliance with Ethics Guidelines. This\narticle is based on previously conducted studies\nand does not contain any new studies with\nhuman participants or animals performed by\nany of the authors.\nData Availability. The datasets generated\nduring and/or analyzed during the current\nstudy are available from the corresponding\nauthor on reasonable request.\nOpen Access. This article is licensed under a\nCreative Commons Attribution-NonCommer-\ncial 4.0 International License, which permits\nany non-commercial use, sharing, adaptation,\ndistribution and reproduction in any medium\nor format, as long as you give appropriate credit\nto the original author(s) and the source, provide\na link to the Creative Commons licence, and\nindicate if changes were made. The images or\nother third party material in this article are\nincluded in the article’s Creative Commons\nlicence, unless indicated otherwise in a credit\nline to the material. If material is not included\nin the article’s Creative Commons licence and\nyour intended use is not permitted by statutory\nregulation or exceeds the permitted use, you\nwill need to obtain permission directly from the\ncopyright holder. To view a copy of this licence,\nvisit http://creativecommons.org/licenses/by-\nnc/4.0/.\nREFERENCES\n1. Fan XM, Ren YF, Fu X, et al. Gabapentin has longer-\nterm efficacy for the treatment of chronic pelvic\npain in women: a systematic review and pilot meta-\nanalysis. Pain Ther. 2021;10:1673–89. https://doi.\norg/10.1007/s40122-021-00330-4.\n2. Horne AW, Vincent K, Hewitt CA, et al. Gabapentin\nfor chronic pelvic pain in women (GaPP2): a mul-\nticentre, randomised, double-blind, placebo-con-\ntrolled trial. Lancet. 2020;396:909–17. https://doi.\norg/10.1016/S0140-6736(20)31693-7.\n3. Lewis SC, Bhattacharya S, Wu O, et al. Gabapentin\nfor the management of chronic pelvic pain in\nwomen (GaPP1): a pilot randomised controlled\ntrial. PLoS ONE. 2016;11: e0153037. https://doi.\norg/10.1371/journal.pone.0153037.\n4. Putzke JD, Richards JS, Kezar L, Hicken BL, Ness TJ.\nLong-term use of gabapentin for treatment of pain\nafter traumatic spinal cord injury. Clin J Pain.\n2002;18:116–21. https://doi.org/10.1097/\n00002508-200203000-00007.\n5. Biggs JE, Boakye PA, Ganesan N, et al. Analysis of\nthe long-term actions of gabapentin and pregabalin\nin dorsal root ganglia and substantia gelatinosa.\nJ Neurophysiol. 2014;112:2398–412. https://doi.\norg/10.1152/jn.00168.2014.\n6. Busse JW, Wang L, Kamaleldin M, et al. Opioids for\nchronic noncancer pain: a systematic review and\nmeta-analysis. JAMA. 2018;320:2448–60. https://\ndoi.org/10.1001/jama.2018.18472.\n7. Kemp JL, Mosler AB, Hart H, et al. Improving\nfunction in people with hip-related pain: a sys-\ntematic review and meta-analysis of physiothera-\npist-led interventions for hip-related pain. Br J\nSports Med. 2020;54:1382–94. https://doi.org/10.\n1136/bjsports-2019-101690.\n8. Lim EC, Tay MG. Kinesio taping in musculoskeletal\npain and disability that lasts for more than 4 weeks:\nis it time to peel off the tape and throw it out with\nthe sweat? A systematic review with meta-analysis\nfocused on pain and also methods of tape applica-\ntion. Br J Sports Med. 2015;49:1558–66. https://doi.\norg/10.1136/bjsports-2014-094151.\n9. Salaffi F, Stancati A, Silvestri CA, Ciapetti A, Grassi\nW. Minimal clinically important changes in\nchronic musculoskeletal pain intensity measured\non a numerical rating scale. Eur J Pain. 2004;8:\n283–91. https://doi.org/10.1016/j.ejpain.2003.09.\n004.\n10. Horowitz MA, Kelleher M, Taylor D. Should\ngabapentinoids be prescribed long-term for anxiety\n324 Pain Ther (2022) 11:321–325\n\nand other mental health conditions? Addict Behav.\n2021;119: 106943. https://doi.org/10.1016/j.\naddbeh.2021.106943.\n11. McAnally H, Bonnet U, Kaye AD. Gabapentinoid\nbenefit and risk stratification: mechanisms over\nmyth. Pain Ther. 2020;9:441–52. https://doi.org/10.\n1007/s40122-020-00189-x.\nPain Ther (2022) 11:321–325 325","source_license":"CC0","license_restricted":false}