Prolonged morphine treatment relieves thermal hyperalgesia in rats with sciatic nerve constriction injury

We examined the effects of chronic morphine treatment with regular intermittent administration in a modified chronic constriction injury (CCI) model of the rat sciatic nerve originally introduced by Bennett and Xie. A painful neuropathy was induced over the left hind limb with sciatic nerve ligation, and sham surgery was done on the opposite side in male Sprague-Dawley rats. Paw-with-drawal latency (PWL) was obtained one day before surgery (pre-op baseline) and on the fourth day after surgery (post-op) to assure the development of thermal hyperalgesia. Morphine hydrochloride (5, 10, 15, and 20 mg/kg per day) was subcutaneously administered for 7 days to four experimental groups. The control group received normal saline rather than morphine under the same injection protocol. PWLs were evaluated on days 5, 7, 9, and 11 of the treatment. PWL decreased to 50-60% of the pre-op baseline or sham limb on the fourth day after surgery. Morphine's ability to reverse PWL appeared dose-related, and no tolerance developed during treatment with chronic intermittent administration. This may indicate that prolonged use of intermittently-administered morphine can be a feasible regimen for relief of neuropathic pain.