Changes Of The Rat's Spinal Astrocytes In The Development Of Chronic Morphine Tolerance

Objective: To investigate the changes of the spinal astrocytes in the development of morphine tolerance in rats.Methods: S-D Rats were randomly divided into seven groups: subcutaneous control group(A group),intrathecal control group(B group),intrathecal PPT group(C group) , systemically morphine tolerance group(D group) , systemically morphine tolerance + PPT group(E group),spinal morphine tolerance group(F group) ,spinal morphine tolerance+PPT group(G group). Tolerance to systemic morphine was induced by morphine hydrochloride (10mg/kg i. h) for 9 consecutive days. The spinal tolerance rats were implanted with polyethylene (PE-10) catheters into the lumbar spinal cord. After 4 days of recovery, morphine (10μg/10μl) was delivered intrathecally twice daily for 5 consecutive days to induce spinal tolerance. PPT was given at a dose of 10μg/rat(i.t). Negative control for morphine was saline. Analgesic effect of morphine was evaluated by the conventional paw withdrawal test. Changes in paw withdrawal latency (PWL) were expressed as percentage of maximal possible effect (MPE%). After the experiments L4-5 spinal cord segments were removed. The changes of the spinalastrocytes response to chronic morphine tolerance were examined by immunohistochemistry of glial fibrillary acidic protein (GFAP).RESULTS: Group D and group F were repeated administration of morphine led to significant increase in GFAP, a specific marker for astroglial cells, in the spinal cord. Glial activation was characterized by hypertrophy and increased ramification. In the group E and group G, when chronic morphine was delivered in combination with propentofylline, a specific and reversible inhibition of glial cells, morphine tolerance was partly but significantly attenuated as measured by behavioral test and the increase in spinal GFAP immunostaining was also greatly blocked.Conclusion: Repeated administration of morphine led to significant increase in GFAP. This increase was attributed primarily to hypertrophy of astroglial cells rather than their proliferation or migration. Propentofylline may partly block the development of morphine tolerance by inhibiting the activity of astrocytrs. The present investigation provides the evidence for the role of glial cells in the development of morphine tolerance in vivo.