Morphine Reduces Leukocyte Migration in vitro

Objectives: The use of opioids such as hydrocodone or codeine (3-methylmorphine) prior to, during or after oral surgery may affect the healing process. Similarly, overuse and abuse of opioids may affect wound healing. Opioids have varying effects on immune cell function and activity. Leukocyte recruitment and migration into sites of damaged tissue lead to debridement and remodeling, contributing to repair. We hypothesized that opioids such as morphine could directly affect leukocyte migration thereby altering recruitment and wound healing. We sought to assess the effect of morphine on leukocyte chemotaxis towards tumor cell derived factors using the transwell system.

Methods: Approximately 5x10⁵ saline or morphine (1.0μM, 16-24hrs 37⁰C) treated and CFDA (10μM, 15 minutes 37⁰C) labeled PLB985 human myelomonocytic cells were loaded into top wells of the transwell set-up. Bottom wells contained either 5%FBS+RPMI1640 or ovarian carcinoma derived conditioned media (MA148-CM). PLB985 cells were allowed to migrate through collagen coated, 3.0μM pores from top wells into bottom wells for 6hrs in a humidified 37⁰C, 5% CO₂ incubator. Migrated cells were collected and relative fluorescence determined using a fluorescent plate reader. The effect of morphine on granulocyte migration was further assessed on freshly isolated saline and morphine pretreated granulocytes isolated from human blood.

Results: When compared to saline, morphine significantly reduced the migration of PLB985 cells towards tumor cell derived conditioned media (p<0.05). Similarly, granulocytes isolated from human blood, showed on an average a 46% reduction in chemotaxis to MA148-CM following morphine treatment (p<0.033).

Conclusions: Opioids can reduce leukocyte migration in vitro. This potentially reduces leukocyte recruitment and may delay wound healing. Further examination is required to determine a possible mechanism.