Glial cells play an important role in producing and maintaining pain. They also play an important role in influencing how well opioid pain relievers function.
It has been noted that taking opioids daily often results in very similar symptoms to how someone might feel with the flu. At first the opioids improve pain control, but soon they seem to become ineffective for most people, so they have to be increased. If you have been taking opioids for pain, think back to the time that you first began taking them. Are you taking the same dose and the same quantity now? Or are you taking more? Do they give you the same pain relief they did when you first started? What happens when you miss a dose? Have you noticed that things seem to hurt more? Before you answer, think about a time when you may have stubbed your toe, or burned your hand since you’ve been taking opioids. Probably, it caused quite a bit more pain than it did before you started taking these medications. When someone takes opioids over a prolonged period of time, they begin to experience the same hypersensitivity to pain that occurs from injury or illness as was described in the previous post. This similarity led to the evaluation of glial cell function in the face of opiate use and what has been found is that glial cells activate in the same fashion in response to opioids as they do to stress from other causes. (Watkins LR, Hutchinson MR, Johnston IN, Maier SF. Glia: novel counter-regulators of opioid analgesia. Trends Neurosci 2005;28:661–9.).
As a person takes opioids, microglia and astrocytes activate and begin to produce cytokines and take other actions to sensitize the nervous system. The effects of sensitization are most apparent during withdrawal when increased pain is experienced if you miss a dose of opioid. Therefore, the glia inhibit the pain relieving effects of opioids. It is also being learned that in some cases, the addition of a glial cell inhibitor can enhance the activity of opioids and reduce the development of pain hypersensitivity associated with the use of opioids. We are beginning to explore the administration of ultra low dose naltrexone or naloxone with opioids and it appears that this may enhance the benefits of opioids. This was first noted with a couple of opioids that were formulated with naloxone and it was found that this combination worked better than just administering the opioid alone