The Effects of Morphine on Sensory and Motor Functions After A Spinal Cord Injury

Texas A&M University System, College Station TX

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Abstract

DESCRIPTION (provided by applicant): Spinal cord injury affects over a quarter of a million people in the United States alone, with a variety of devastating consequences including loss of bowel, bladder, sexual, and limb function, and neuropathic pain. Considerable research is now focused on finding ways to ameliorate the functional consequences of injury.Surprisingly, however, little is known about the consequences of first-line analgesics on the long-term recovery of motor and sensory function. Opiates are given soon after an injury and are used by a significant proportion of the spinally-injured population, but we do not know what impact they have on functional recovery. The current proposal aims to address this issue. We will look at the functional consequences of repeated morphine exposure after a spinal contusion injury using male, Sprague-Dawley rats. Preliminary data suggests that even a single dose of morphine can have a lasting effect on both sensory function (producing a tactile allodynia) and lesion size. We have also shown that uncontrollable stimulation undermines sensory and motor function, and interacts with morphine treatment, producing an increase in mortality. The proposed experiments will extend this research using a clinically relevant, extended morphine treament regime. Using a wide range of behavioral tests we will compare the motor and sensory recovery of rats given a single injection of morphine, repeated morphine injections (0, 2.5, 5,10, 20 mg/kg), or saline over a 3 week period. Because the consequences of morphine treatment may be most evident in the presence of an environmental challenge, half the subjects in each condition will receive 30 min of uncontrollable stimulation 1 day after injury. Functional recovery will be monitored for 6 weeks. The proposed studies, therefore, will use a 2 (acute vs extended morphine) x 5 (dose) x 2 (shock vs unshock) experimental design to elicidate the functional consequences of morphine. The hypothesis is that extended morphine treatment will undermine recovery. These effects may be most evident after a high dose and in subjects that receive uncontrollable stimulation. This initial study will lay the foundation for many future research projects looking at 1) the molecular mechanisms underlying the effects of morphine, 2) effects of injury variables such as lesion size, and 3) impacts of other first-line analgesics such as NSAIDS, acetaminophen, and gabapentin on the recovery of function after a spinal cord injury.