Strain-specific Differences in Modulatory Effects of Morphine on Peritoneal Inflammation in Mice

It has been previously shown that local administration of a high dose of morphine together with a proinflammatory agent has anti-inflammatory effects in several (but not all) strains of mice. In the present paper, behavioural and cellular consequences of morphine co-injection are compared between several strains of mice with zymosan-induced peritonitis. Males of C57C3H, Swiss, Balb/c, C57BL/6, and CBA strains were ip injected with Zymosan (40 mg/kg) and/or morphine at 0, 5, 10, 20 mg/kg without or with naltrexone pretreatment. Early stages of Zymosan-induced peritonitis were connected with intraperitoneal accumulation of leukocytes (mainly PMNs), pain symptoms (body writhes of strain-specific frequency: C57C3H>CBA>Swiss>>Balb/c∼C57BL/6), and sedation (significant in Swiss and Balb/c). Morphine co-injection abolished pain symptoms at all doses in every investigated strain, and restored locomotor activity or induced hyperlocomotion in a dose- and strain-specific manner. The highest dose of morphine inhibited intraperitoneal accumulation of peritoneal leukocytes (PTLs) including polymorphonuclear cells (PMNs) in all but the CBA strain of mice. Anti-inflammatory and anti-nociceptive effects of morphine were reversed in naltrexone pre-treated animals. The pre-incubation of Swiss but not CBA leukocytes with morphine inhibited cell chemotaxis towards zymosan-activated serum. In conclusion, morphine exerts various strain-specific effects on peritonitis.