Comparing effects of central and peripheral methadone on a rat ulcerative colitis model

Introduction There are several lines of evidences on the roles of opioids in inflammatory mechanisms in the gastrointestinal tract as well as other parts of the body Objectives This study contrasts effects of central and peripheral routs of methadone administration on acute colon inflammation in male rats. Methods Ulcerative colitis was induced by intrarectal acetic acid 4%. Methadone was injected subcutaneously (s.c.) 5 and 10 mg/kg and intracerebroventriculary (i.c.v.) 50 and 300 ng/rat. Opioid antagonists were employed, methylnaltrexone (MNTX) a peripherally acting (5 mg/kg, i.p.) and naltrexone (NTX), peripherally and centrally acting (5 mg/kg, i.p. and 10 ng/rat, i.c.v.), before methadone (10 mg/kg, s.c. and or 300 ng/rat, i.c.v.). NTX 5 mg/kg, i.p. and NTX 10 ng/rat, i.c.v. were administered prior to methadone 10 mg/kg, s.c. and methadone 300 ng/rat, i.c.v., respectively; MNTX (5 mg/kg, i.p.) was injected prior to methadone 10 mg/kg, s.c. Seventy-two hrs subsequent to the colitis, macroscopic and microscopic mucosal lesions and the colonic levels of tumor necrosis factor-alpha (TNF-α) and interlukin-1β (IL-1β) were determined. Results Methadone 300 ng/rat, i.c.v., and 5 & 10 mg/kg, s.c. improved the macroscopic and microscopic parameters through opioid receptors. Also, a significant reduction in TNF-α and IL-1β was observed. Peripherally and centrally NTX significantly reversed methadone 10 mg/kg s.c. anti-inflammatory effects while MNTX could not completely reverse this effect. Moreover, centrally administered methadone (300 ng/rat) showed anti-inflammatory effect which was reversed by central NTX (10 ng/rat). ConclusionMethadone protective effect in treatment of inflammatory bowel disease may act mainly through the central opioid receptors

Keywords:

Ulcerative colitis , Methadone , Acetic acid , Opioid receptors , Brain-gut axis