title: Effect of topical administration of tramadol on corneal wound healing in rats.
abstract: In this study, we aimed to investigate the effects of topical tramadol administration on corneal wound healing, and examine ophthalmic structures and intraocular pressure 7 days after tramadol administration. The experiments were conducted on eight male Wistar rats (250-300 g). After ophthalmic examination, epithelial cell layers in the central cornea were wounded. Rats received 30 μL of tramadol hydrochloride in one eye (Group Tramadol) and the same volume of vehicle in the other (Group Control) every 12 h for 7 days. Both eyes were stained with fluorescein dye, photographed, and wound area was calculated every 8 h until complete healing was observed. Eye blink frequency and corneal reflex tests were measured before and after drug administrations. After 7 days, slit lamp biomicroscopy, fundoscopy, Goldmann applanation tonometry, and histological evaluation were performed. There was no difference in the corneal wound healing rates between the tramadol and control groups. Reduction in wound area over time was also similar; group-time interaction was insignificant (F = 738.911; p = 0.225). Tramadol application resulted in blinking and blepharospasm for 30 s, but vehicle did not. Corneal reflex was intact and eye blink frequency test results were similar in all measurement times in both groups. Slit lamp biomicroscopy, fundoscopy, and intraocular pressures were within normal range. Corneal cells appeared unaffected by the repeated doses of tramadol for 7 days. Topical tramadol application on the cornea did not cause any side effect, except for initial temporary blinking and blepharospasm. Corneal wound healing was not affected, either.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Giresun University Medical Faculty, Nizamiye Yerleskesi, Orhan Yılmaz Caddesi, Mumcular Sokak No:1, Merkez, 28200, Giresun, Turkey. ozguncuvas@yahoo.com.
authors.forename: Ozgun
authors.initials: O
authors.lastname: Cuvas Apan
authors.affiliation: Department of Ophthalmology, Giresun University Medical Faculty, Giresun, Turkey.
authors.forename: Murat Atabey
authors.initials: MA
authors.lastname: Ozer
authors.affiliation: Department of Clinical Pharmacology, Giresun University Medical Faculty, Giresun, Turkey.
authors.forename: Selcuk
authors.initials: S
authors.lastname: Takir
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Giresun University Medical Faculty, Nizamiye Yerleskesi, Orhan Yılmaz Caddesi, Mumcular Sokak No:1, Merkez, 28200, Giresun, Turkey.
authors.forename: Alparslan
authors.initials: A
authors.lastname: Apan
authors.affiliation: Department of Pathology, Giresun University Medical Faculty, Giresun, Turkey.
authors.forename: Demet
authors.initials: D
authors.lastname: Sengul
mesh_terms: D000287:Administration, Topical; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001764:Blepharospasm / Q000139:chemically induced; D001767:Blinking / Q000187:drug effects; D065306:Corneal Injuries / Q000188:drug therapy*; D004195:Disease Models, Animal; D015590:Fluorophotometry; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D009883:Ophthalmic Solutions; D051381:Rats; D017208:Rats, Wistar; D066167:Slit Lamp; D014065:Tonometry, Ocular; D014147:Tramadol / Q000009:adverse effects / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D009883:Ophthalmic Solutions; D014147:Tramadol
keywords: Administration; Cornea; Topical; Tramadol; Wound healing
references.citation: Vet Ophthalmol. 2002 Jun;5(2):127-35
references.pmid: 12071871
references.citation: J Pharm Sci. 1998 Dec;87(12):1479-88
references.pmid: 10189253
references.citation: J Clin Invest. 2004 May;113(9):1344-52
references.pmid: 15124026
references.citation: Am J Health Syst Pharm. 1997 Mar 15;54(6):643-52
references.pmid: 9075493
references.citation: Am Fam Physician. 2013 Jan 15;87(2):114-20
references.pmid: 23317075
references.citation: Vet Clin North Am Small Anim Pract. 2004 May;34(3):707-23
references.pmid: 15110980
references.citation: Anesth Analg. 2008 Jun;106(6):1890-6
references.pmid: 18499628
references.citation: J Pharm Pharmacol. 2008 Sep;60(9):1149-54
references.pmid: 18718117
references.citation: AAPS J. 2010 Sep;12(3):348-60
references.pmid: 20437123
references.citation: Pain. 2010 Jun;149(3):522-8
references.pmid: 20403666
references.citation: Br J Anaesth. 1995 Mar;74(3):247-9
references.pmid: 7718365
references.citation: Pharm Res. 2001 Nov;18(11):1497-508
references.pmid: 11758755
references.citation: Pain. 2003 Oct;105(3):455-65
references.pmid: 14527706
references.citation: Brain Res. 2006 Apr 26;1085(1):87-94
references.pmid: 16564032
references.citation: Fundam Clin Pharmacol. 1999;13(2):220-5
references.pmid: 10226767
references.citation: Anaesthesia. 1992 Apr;47(4):291-6
references.pmid: 1519677
references.citation: Expert Opin Drug Saf. 2007 Nov;6(6):637-40
references.pmid: 17967152
references.citation: Anesth Analg. 2001 Jun;92(6):1547-51
references.pmid: 11375844
references.citation: Eur J Ophthalmol. 2007 Nov-Dec;17(6):976-8
references.pmid: 18050127
references.citation: Drug Alcohol Depend. 1991 Jan;27(1):7-17
references.pmid: 2029860
references.citation: Pain. 1983 Jun;16(2):109-10
references.pmid: 6877845
references.citation: Braz J Med Biol Res. 2012 Feb;45(2):147-52
references.pmid: 22183244
references.citation: Am J Vet Res. 2003 Jul;64(7):813-8
references.pmid: 12856763
references.citation: Top Companion Anim Med. 2015 Sep;30(3):74-80
references.pmid: 26494498