Examining the Interaction of Pain and Morphine
Nicole Crysdale
Abstract:
Few studies to date have examined the neurological differences in the effects of acute morphine administration on old vs. young rats. This research used acute morphine administration on young and old rats as well as acute pain administration to observe the neurological differences caused by age. It is our hypothesis that the decreased efficacy of opioids in older rats is due to glial priming. This glial priming is presumably caused by an increased glial activation and thus increased potential for fractalkine signaling. We observed a dramatic increase in glial activation caused by acute morphine administration in old rats, but the same dosage only slightly increased glial activation in young rats. Our results also showed a decrease in the paw withdrawal latency 60 minutes after morphine administration in old rats, when young rats experienced an increase in paw withdrawal latency. This leads us to conclude that morphine has different neurological affects depending on the age of the rat to which it was administered and this is most likely due to glial priming. The results of this study also indicate that there must be different glial activation pathways in the young than the old and therefore the glial activation pathway changes with age. This confirms our hypothesis that glial priming occurs in older rats and that this increased glial activation is caused by an increase in the potential for fractalkine signaling and results in the decreased efficacy of morphine.
Introduction:
Opioids are the most widely used treatment for pain-relief throughout the world. They are specified by the World Health Organization as the first line treatment for acute pain. Morphine, once the most commonly prescribed opiate, and was chosen for study in this research as it was the first opioid characterized and is considered the prototypic opioid. Opioids bind to opioid receptors and those found in the dorsal horn of the spinal cord are very important for morphine analgesia. Morphine acts by presynaptic inhibition to block the release of substance P and glutamate, known pain neurotransmitters (3). Blocking the action of these neurotransmitters disrupts the nociceptive signal pathway and results in pain relief. Chronic use of opioids leads to decreased analgesia from the same dose leading to a phenomenon called tolerance. Recent evidence has suggested that this may be due to glial activation (4). Glial cells are the support cells of the nervous system and provide structure, nourishment, and waste removal as well as many other important functions that create an optimal-functioning environment for neurons (3). The glial activation that this research focuses on occurs in microglia cells, which are phagocytic and serve as the protective immunity cells within the brain and spinal cord. Increased glial activation in response to morphine exposure is called opioid tolerance and is a serious challenge when it comes to treating chronic pain (4). With prolonged exposure to an opioid, it will progressively lose its effectiveness as a pain reliever. One proposed mechanism by which the efficacy of opioids is decreased involves glial activation in the spinal cord caused by an increased potential for fractalkine signaling. Fractalkine is a type of chemokine, a glycoprotein that is chemoattractant and serves as a signal to attract monocytes and T cells. Fractalkine receptors are only expressed by microglia (1). An increase in the amount of fractalkine receptors and ligands increases the potential for fractalkine signaling. The binding of fractalkine receptor to a fractalkine ligand causes glial activation, which opposes opioid analgesia and leads to a decreased threshold for and increased reaction intensity to painful stimuli (4). Chronic morphine exposure causes tolerance by increasing the number of fractalkine receptors on the microglia, thus priming them to react against the increasing amount of fractalkine....continued in print edition.
