Opiate abuse on the rise, a problem for pain management?

Drugmonkey, via Kevin Z, points out a map of the US showing rates of prescription narcotic use in the US by state and rather alarming trends in increases in narcotic use nearly across the board (from the Las Vegas Sun). Anyone with any medical knowledge can look at the list of drugs assessed by the Las Vegas Sun reporters and recognize that the compounds under scrutiny are pain medications. All of them are opiates. As we all know opiates are commonly used to treat acute and chronic pain and they are generally the first class of compounds (with the possible of exception of NSAIDs) that a doctor will consider to control pain.

The data presented in the interactive map show that there are wide variations in specific opiate use across the US but the general trend is a large increase in opiate use in nearly every state. This can generally be interpreted as an increase in opiate abuse nation-wide. I see no reason to dispute this point as it is well supported by media reports and population-based clinical studies. My reason for bringing this up is that beyond (and likely connected to) the increase in opiate abuse is a looming problem for pain management connected to opiate over-use.

Let us begin with an example of why this is a problem. Migraine. Migraine is one of the most common forms of chronic pain affliction and it is commonly treated by NSAIDs, triptans and/or opiates. Recent evidence suggests that medication use can exacerbate migraine frequency and intensity and opiates appear to be a major contributor to this problem. For instance, Rami Burstein’s group has shown that I.V. NSAIDs (ketorolac, specifically) can be effective in reducing the intensity of migraine and in reducing the body-wide allodynia that often accompanies a migraine attack. However, in their study they noted that there was a subset of patients that did not respond to ketorolac and whose headaches (and allodynia) were very difficult to treat: patients with a history of opiate use. Subsequent studies (some of which are circling the meetings and not published yet) have shown that opiate use can exacerbate migraine frequency and intensity and that opiates are likely to be the strong contributers to medication over-use headache. Opiates are analgesics, why would this happen.

To begin to understand the problem that chronic opiate use (or opiate abuse) creates for pain management we need to turn to pre-clinical studies. It is well known that opiates have positive reinforcing effects and that these properties contribute strongly to opiate abuse. Opiates also have negative reinforcing effects (such as opiate withdrawal) which are a further problem in treating opiate abuse and these properties also contribute to the abuse potential of opiates. In addition to these reinforcing effects, opiates are capable of stimulating a hyperalgesic state in both humans and animals. While the initial effects of opiate administration are analgesia, as opiate administration becomes chronic, opiates begin to lose their analgesic effect and can actually stimulate a state of paradoxical pain (in humans) or hyperalgesia (in animals). Pre-clinical (animal studies) work has shown that chronic opiates can create adaptations in the nervous (and immune) systems that exacerbate rather than decrease pain. For instance, chronic morphine treatment can increase nociceptor sensitivity and local cytokine production following incision, a common post-surgical pain model. These preclinical findings are paralleled by clinical data showing that opiate use prior to surgery can increase recovery time and the duration of pain after surgery.

Another series of preclinical studies have shown that chronic opiate exposure 1) induces changes in the expression of pro-nociceptive neurotransmitters in peripheral sensory neurons, 2) alters spinal neurotransmission in a manner similar to central sensitization and 3) alters descending pain facilitation such that pain transmission is amplified. Taken together, these studies indicate that opiate abuse is liable to create a hyperalgesic state in humans and that this hyperalgesic state can worsen pre-existing pain conditions and make treating future pain conditions more challenging. Because opiates remain one of the primary classes of drugs for acute and chronic pain treatment this creates an obvious quandary for pain management in a society where opiate abuse is on the rise.

I write all of this primarily to emphasize that the problem of increasing opiate abuse in the US (and throughout the world for that matter) has the potential to create additional problems that are not immediately obvious to the casual observer (or even to the highly-involved funding agency). I would not care to advocate a position of not prescribing opiates for pain control. On the other hand, I would argue that increased awareness on the problem of opiate abuse and opiate-induced pain can be utilized as an educational tool in helping pain patients better manage their pain and avoid problems that can occur with long-term use of these addictive compounds. Finally, this is yet another example of why new and better analgesics are so desperately needed.