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

Abstract

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.