Chronic Pain

How Opioids Can Worsen Pain

The use of chronic opioids leads to either tolerance or sensitization.  This results in loss of efficacy either way and results in pronociception either way. The nociceptive system works to maintain responsiveness of the system. The longer you take opioids to blunt chronic pain, the more likely you are to experience enhanced pain as the body tries to restore normal sensory function.

Preclinical evidence. Thermal hyperalgesia has been recognized back to the 1980’s in the animal sciences. Hyperalgesia is defined as an exaggerated response to painful stimulation.  Hyperalgesia is manifested as an exaggerated response to hot temperatures.  The animals who experienced hyperalgesia could tolerate less heat than normal animals not suffering from hyperalgesia.  Hyperalgesia can be demonstrated following the injection of morphine into the spinal fluid of rats over several days. The duration of the hyperalgesic effect extended beyond the time that the morphine was discontinued which implied changes in the nervous system.  [Vanderah et al. J Neurosci. 2000 Sep 15;20(18):7074-9 ,  Mao J et al. J Neurosci. 2002 Sep 15;22(18):8312-23.] Other opiates such as Fentanyl and Heroin have the same effect. [Celerier et al, J Neurosci. 2001 Jun 1;21(11):4074-80.]

Clinical Implications: Repeated use of opioids can lead to a pathological pain state. Decreased analgesic efficacy can be seen as early as following a single dose. [ Cooper et al. 1997, Vinik and Kissin 1998, Guignard et al 2000.] Patients not given opioids interoperatively required fewer opioids post operatively.

When patients with low back pain were tested for hyperalgesia with a cold pressor test, it was found that patients with low back pain alone had much better pain tolerance than patients who had low back pain and had been treated with opioids. [Chu et al 2006.]

It appears that chronic back pain alone causes little wind up when compared to healthy individuals, but exposure to opioids resulted in dramatic thermal allodynia and temporal summation. The patients simply had more pain. They felt pain with less stimulation and their pain was more severe.

In an effort to relieve pain in these patients by treating them with opioid pain relievers, the patients developed worse pain and lowered pain tolerance in a short period of time.


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