Chronic Pain

Glial Cells and Opioids

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

 

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Chronic Pain

How do Glial Cells Effect Pain?

We know that glial cells ramp up their effects in response to pain. We know that they can be responsible for enhancing pain via direct actions on the nervous system as well as indirect actions, such as the production of chemical inflammatory compounds such as cytokines. It is known that these inflammatory cytokines enhance the transmission of pain via nerves.  They serve to turn up the volume on the pain signals being transmitted to the brain. We also know that we can reduce pain by suppressing glial cells. Two medications that I work with to treat pain have direct action at the glial cell. The first is naltrexone.  Naltrexone is a drug that is primarily used to inhibit the effects of opioids (morphine and morphine like medications). Minocycline is an antibiotic.  Both of these drugs are known to suppress the activity of glial cells and both are effective at reducing certain types of pain.

Putting all of this together makes it much more clear what is happening. Glial cells such as astrocytes and microglia act to maintain normal central nervous system function. If a person is suddenly exposed to pain or illness, the glial cells will react and change their function. They begin to participate in the pain or illness by increasing their numbers and changing their function from a support role to an enhancing role. They enlarge and they form more glial cells and they begin to enhance the pain transmission abilities of the nervous system. They sensitize the nervous system to stimulation.

Think back to a time when you were ill with a bad cold or flu. Remember how your body ached? Remember how you didn’t want to be touched, or talk, or even read or look out the window? Your nervous system was hypersensitized and all these stimulation-sight, touch, sound-became painful. This is what glial cells do to worsen your pain. They do it via chemical mediators that signal them to switch their role from support to enhancement of suffering. This is important to help the body heal. It encourages you to go lie down, conserve your energy and allow the body to direct its efforts at healing you, rather than having to maintain the normal activities that result from your normal busy daily schedule.

If I give you a drug to block the activity of glial cells, I can reduce these symptoms, so I know the glial cells are responsible, at least in part, for how you feel when you are ill or injured.

 

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