Investigation of Inflammatory Effects of Morphine and Fentanyl on Early Wound Healing in Rats: an Experimental Study.

Bibliographic Details
Title: Investigation of Inflammatory Effects of Morphine and Fentanyl on Early Wound Healing in Rats: an Experimental Study.
Alternate Title: Ratlarda Morfin ve Fentanil’in Erken Dönem Yara İyileşmesinde İnflamatuar Etkilerinin İncelenmesi.
Authors: Canakci, Ebru1 canakciebru@gmail.com, Catak, Tuba2, Saltali, Ali Ozgul2, Sahin, Abdullah Alper3, Celik, Muruvvet Akcay4, Bayrak, Tulin5, Bayrak, Ahmet5
Source: Gazi Medical Journal. 2023, Vol. 34 Issue 2, p175-179. 5p.
Subject Terms: *FENTANYL, *HEALING, *MORPHINE, *SURGICAL site, *WOUND healing
Abstract (English): Objective: It has been shown that increase in proinflammatory cytokines IL-1α, IL1-β, IL-6, and TNF-α strongly increased during the acute inflammatory phase of wound healing. In the present study, we aimed to investigate the effects of local morphine and fentanyl on TNF-α, IL-1β levels, which are important markers of inflammatory response, and wound healing based on histopathological scores in an experimental wound model created on rats. Methods: 18 male Wistar-Albino rats were included in this study. A 1-cm longitudinal surgical incision containing skin and subcutaneous connective tissue was made in the dorsal region. 3 ml 1500 mcg morphine was injected to the incision line for Group M (n=6). 3 ml diluted fentanyl and 15 mcg fentanyl was injected (n=6) Group F. 3 ml of physiological saline (n=6) was injected for Group C The skin and subcutaneous tissues were sutured with a 4/0 silk thread. A 0.5 ml of blood sample was collected and centrifuged 30 minutes after the procedure. Plasma TNF-α and IL1-β levels were assessed. On the 7th day after the process, a biopsy sample was obtained from the incision line and histopathological wound healing scores were evaluated. Results: A difference was found in the mean IL1-β levels between the groups (p=0.009). While the mean value was determined as 117.11 in the control group, it was 195.47 in the Morphine group and 154.89 in the Fentanyl group. While the control group had a lower mean value than the Morphine group, no difference was found between the Fentanyl group and the control and morphine groups. TNF-α, active inflammation (AI),chronic inflammation (CI), Granulation (G), and Fibrosis (F) scores did not differ between the groups (p values: 0.995, 0.365, 0.057, 0.056, and 0.421, respectively). In the morphine group, a strong positive correlation was only found between the CI score and TNF-α (r=0.828; p<0.001).A strong negative correlation was found between the F score and IL1-β in the fentanyl group (r=-0.828; p<0.001). Conclusions: It has been concluded that morphine and fentanyl play an active role in the acute phase of wound healing and accelerate the migration of polymorphonuclear leukocytes to the wound site. It can be said that opioids contribute to wound healing by exerting immunomodulatory effects, far beyond their role in reducing postoperative pain. We believe that our study will shed light on prospective clinical studies in this regard. [ABSTRACT FROM AUTHOR]
Abstract (Turkish): Giriş ve Amaç: Yara onarımında proinflamatuar sitokinler olan IL-1α, IL1-β, IL-6 ve TNF-α artışının, iyileşmenin akut inflamatuar süreci boyunca güçlü bir şekilde arttığı gösterilmiştir. Bu çalışmadaki amacımız, ratlarda oluşturulan deneysel yara modelinde,lokal morfin ve fentanil uygulamasının inflamatuar yanıtın önemli belirteçlerinden olan TNF-α, IL-1β, düzeyleri ile yara iyileşmesi histopatolojik skorlar üzerine olan etkilerini araştırmaktır. Materyal ve Metod: Çalışmaya 18 adet erkek Wistar-Albino rat dahil edildi. Sırt bölgesinde 1 cm’lik cilt ve ciltaltı bağ dokusunu içeren longitüdinal cerrahi kesi yapıldı. İnsizyon dudaklarına 3 ml 1500 mcg morfin Grup M’ye (n=6) yapıldı. Grup F’ye 3 ml sulandırılmış fentanil 15 mcg fentanil (n=6) yapıldı. Grup K’ya ise serum fizyolojik 3 ml (n=6) verildi. 4/0 ipek iplik ile cilt ve cilt altı dokular karşılıklı birleştirildi. İşlem sonrası 30.dakikada 0.5ml kan örneği alınarak santrifüj edildi. Plazma TNF-α, IL1-β düzeylerine bakıldı. İşlem sonrası 7.günde deneklerin insizyon hattından biyopsi alındı ve histopatolojik olarak yara iyileşmesi skorlarına bakıldı. Bulgular: Gruplara göre IL1-β ortalama değerleri arasında fark vardır (p=0,009). Kontrol grubunda ortalama değer 117,11 iken, Morfin grubunda 195,47 ve Fentanyl grubunda 154,89 olarak elde edilmiştir. Kontrol grubunda elde edilen ortalama değer Morfin grubundan daha düşük iken Fentanyl grubu ile kontrol ve morfin grubu arasında fark yoktur. TNF-α, aktif inflamasyon (AI), kronik inflamasyon (KI), Granülasyon (G) ve Fibrozis (F) skorları gruplara göre farklılık göstermemektedir (p değerleri sırasıyla 0.995, 0.365, 0.057, 0.056 ve 0.421). Morfin grubu içinde de KI skoru ile sadece TNF-α arasında pozitif yönlü güçlü bir ilişki tespit edilmiştir (r=0,828; p<0,001).Fentanyl grubunda F skoru ile IL1-β arasında negatif yönlü güçlü bir ilişki tespit edilmiştir (r=-0,828; p<0,001). Sonuç: Morfin ve fentanilin yara iyileşmesi akut fazında etkin rol oynadığını, yara yerine polimorf nüveli lokositlerin göçünü hızlandırmaktadır diyebiliriz. Opioidler postoperatif ağrıyı kesmek rollerinin çok ötesinde, immünomodülatör etkiyle yara iyileşmesine katkı sağladıkları söylenebilir.Çalışmamızın ileride yapılacak olan klinik çalışmalara ışık tutacağı inancındayız. [ABSTRACT FROM AUTHOR]
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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Investigation of Inflammatory Effects of Morphine and Fentanyl on Early Wound Healing in Rats: an Experimental Study.
– Name: TitleAlt
  Label: Alternate Title
  Group: TiAlt
  Data: Ratlarda Morfin ve Fentanil’in Erken D&#246;nem Yara İyileşmesinde İnflamatuar Etkilerinin İncelenmesi.
– Name: Author
  Label: Authors
  Group: Au
  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Canakci%2C+Ebru%22&quot;&gt;Canakci, Ebru&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;i&gt; canakciebru@gmail.com&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Catak%2C+Tuba%22&quot;&gt;Catak, Tuba&lt;/searchLink&gt;&lt;relatesTo&gt;2&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Saltali%2C+Ali+Ozgul%22&quot;&gt;Saltali, Ali Ozgul&lt;/searchLink&gt;&lt;relatesTo&gt;2&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Sahin%2C+Abdullah+Alper%22&quot;&gt;Sahin, Abdullah Alper&lt;/searchLink&gt;&lt;relatesTo&gt;3&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Celik%2C+Muruvvet+Akcay%22&quot;&gt;Celik, Muruvvet Akcay&lt;/searchLink&gt;&lt;relatesTo&gt;4&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Bayrak%2C+Tulin%22&quot;&gt;Bayrak, Tulin&lt;/searchLink&gt;&lt;relatesTo&gt;5&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Bayrak%2C+Ahmet%22&quot;&gt;Bayrak, Ahmet&lt;/searchLink&gt;&lt;relatesTo&gt;5&lt;/relatesTo&gt;
– Name: TitleSource
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Gazi+Medical+Journal%22&quot;&gt;Gazi Medical Journal&lt;/searchLink&gt;. 2023, Vol. 34 Issue 2, p175-179. 5p.
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: *&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22FENTANYL%22&quot;&gt;FENTANYL&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22HEALING%22&quot;&gt;HEALING&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22MORPHINE%22&quot;&gt;MORPHINE&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22SURGICAL+site%22&quot;&gt;SURGICAL site&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22WOUND+healing%22&quot;&gt;WOUND healing&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract (English)
  Group: Ab
  Data: Objective: It has been shown that increase in proinflammatory cytokines IL-1α, IL1-β, IL-6, and TNF-α strongly increased during the acute inflammatory phase of wound healing. In the present study, we aimed to investigate the effects of local morphine and fentanyl on TNF-α, IL-1β levels, which are important markers of inflammatory response, and wound healing based on histopathological scores in an experimental wound model created on rats. Methods: 18 male Wistar-Albino rats were included in this study. A 1-cm longitudinal surgical incision containing skin and subcutaneous connective tissue was made in the dorsal region. 3 ml 1500 mcg morphine was injected to the incision line for Group M (n=6). 3 ml diluted fentanyl and 15 mcg fentanyl was injected (n=6) Group F. 3 ml of physiological saline (n=6) was injected for Group C The skin and subcutaneous tissues were sutured with a 4/0 silk thread. A 0.5 ml of blood sample was collected and centrifuged 30 minutes after the procedure. Plasma TNF-α and IL1-β levels were assessed. On the 7th day after the process, a biopsy sample was obtained from the incision line and histopathological wound healing scores were evaluated. Results: A difference was found in the mean IL1-β levels between the groups (p=0.009). While the mean value was determined as 117.11 in the control group, it was 195.47 in the Morphine group and 154.89 in the Fentanyl group. While the control group had a lower mean value than the Morphine group, no difference was found between the Fentanyl group and the control and morphine groups. TNF-α, active inflammation (AI),chronic inflammation (CI), Granulation (G), and Fibrosis (F) scores did not differ between the groups (p values: 0.995, 0.365, 0.057, 0.056, and 0.421, respectively). In the morphine group, a strong positive correlation was only found between the CI score and TNF-α (r=0.828; p&lt;0.001).A strong negative correlation was found between the F score and IL1-β in the fentanyl group (r=-0.828; p&lt;0.001). Conclusions: It has been concluded that morphine and fentanyl play an active role in the acute phase of wound healing and accelerate the migration of polymorphonuclear leukocytes to the wound site. It can be said that opioids contribute to wound healing by exerting immunomodulatory effects, far beyond their role in reducing postoperative pain. We believe that our study will shed light on prospective clinical studies in this regard. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label: Abstract (Turkish)
  Group: Ab
  Data: Giriş ve Ama&#231;: Yara onarımında proinflamatuar sitokinler olan IL-1α, IL1-β, IL-6 ve TNF-α artışının, iyileşmenin akut inflamatuar s&#252;reci boyunca g&#252;&#231;l&#252; bir şekilde arttığı g&#246;sterilmiştir. Bu &#231;alışmadaki amacımız, ratlarda oluşturulan deneysel yara modelinde,lokal morfin ve fentanil uygulamasının inflamatuar yanıtın &#246;nemli belirte&#231;lerinden olan TNF-α, IL-1β, d&#252;zeyleri ile yara iyileşmesi histopatolojik skorlar &#252;zerine olan etkilerini araştırmaktır. Materyal ve Metod: &#199;alışmaya 18 adet erkek Wistar-Albino rat dahil edildi. Sırt b&#246;lgesinde 1 cm’lik cilt ve ciltaltı bağ dokusunu i&#231;eren longit&#252;dinal cerrahi kesi yapıldı. İnsizyon dudaklarına 3 ml 1500 mcg morfin Grup M’ye (n=6) yapıldı. Grup F’ye 3 ml sulandırılmış fentanil 15 mcg fentanil (n=6) yapıldı. Grup K’ya ise serum fizyolojik 3 ml (n=6) verildi. 4/0 ipek iplik ile cilt ve cilt altı dokular karşılıklı birleştirildi. İşlem sonrası 30.dakikada 0.5ml kan &#246;rneği alınarak santrif&#252;j edildi. Plazma TNF-α, IL1-β d&#252;zeylerine bakıldı. İşlem sonrası 7.g&#252;nde deneklerin insizyon hattından biyopsi alındı ve histopatolojik olarak yara iyileşmesi skorlarına bakıldı. Bulgular: Gruplara g&#246;re IL1-β ortalama değerleri arasında fark vardır (p=0,009). Kontrol grubunda ortalama değer 117,11 iken, Morfin grubunda 195,47 ve Fentanyl grubunda 154,89 olarak elde edilmiştir. Kontrol grubunda elde edilen ortalama değer Morfin grubundan daha d&#252;ş&#252;k iken Fentanyl grubu ile kontrol ve morfin grubu arasında fark yoktur. TNF-α, aktif inflamasyon (AI), kronik inflamasyon (KI), Gran&#252;lasyon (G) ve Fibrozis (F) skorları gruplara g&#246;re farklılık g&#246;stermemektedir (p değerleri sırasıyla 0.995, 0.365, 0.057, 0.056 ve 0.421). Morfin grubu i&#231;inde de KI skoru ile sadece TNF-α arasında pozitif y&#246;nl&#252; g&#252;&#231;l&#252; bir ilişki tespit edilmiştir (r=0,828; p&lt;0,001).Fentanyl grubunda F skoru ile IL1-β arasında negatif y&#246;nl&#252; g&#252;&#231;l&#252; bir ilişki tespit edilmiştir (r=-0,828; p&lt;0,001). Sonu&#231;: Morfin ve fentanilin yara iyileşmesi akut fazında etkin rol oynadığını, yara yerine polimorf n&#252;veli lokositlerin g&#246;&#231;&#252;n&#252; hızlandırmaktadır diyebiliriz. Opioidler postoperatif ağrıyı kesmek rollerinin &#231;ok &#246;tesinde, imm&#252;nomod&#252;lat&#246;r etkiyle yara iyileşmesine katkı sağladıkları s&#246;ylenebilir.&#199;alışmamızın ileride yapılacak olan klinik &#231;alışmalara ışık tutacağı inancındayız. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Gazi Medical Journal is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder&#39;s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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        Value: 10.12996/gmj.2023.35
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      – Code: eng
        Text: English
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      Pagination:
        PageCount: 5
        StartPage: 175
    Subjects:
      – SubjectFull: FENTANYL
        Type: general
      – SubjectFull: HEALING
        Type: general
      – SubjectFull: MORPHINE
        Type: general
      – SubjectFull: SURGICAL site
        Type: general
      – SubjectFull: WOUND healing
        Type: general
    Titles:
      – TitleFull: Investigation of Inflammatory Effects of Morphine and Fentanyl on Early Wound Healing in Rats: an Experimental Study.
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              Text: 2023
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