Chronic CNS Pain: Challenging and Few Approved Agents
LAS VEGAS, NV—During a symposium on chronic pain and central nervous system disorders at PAINWeek 2012, Charles E. Argoff, MD, CPE, Professor of Neurology and Director of the Comprehensive Pain Center at Albany (NY) Medical Center, told the audience that only a handful of products are currently specifically approved for treating central nervous system lesions. An additional challenge for clinicians is that few studies, all including only small numbers of patients, have produced little hard data on diagnosing and treating chronic CNS pain. This contrasts with the dramatic increase in research in other related areas, such as diabetic neuropathy.
Dr. Arnoff likened the CNS, or the brain and spinal cord, to a computer's central processing unit, with the CNS integrating all of the information of the nervous system. Because of the complexity of the CNS and its varying healing patterns, diagnosing the source of pain can be difficult and there is still little hard data. For example, few studies have examined patients with post-stroke pain. Dr. Arnoff noted that a major change in the definition of CNS pain is a new definition of dysfunction: “dysfunction only exists if a lesion can be documented within the somatosensory system.” Central pain has three main components: pain evoked by stimulation or touching; steady and neuralgic-like pain (pain all the time); and pain that occurs spontaneously.
The use of the term dysfunction has always been problematic because, he asked, “How do you prove where the pain originates?” The source of the pain or existence of pain may be elusive as well; for example, a post-stroke patient may not have any clearly detectable sensory loss. A CNS injury may be maximal or minimal, Dr. Arnoff explained, but “it's not the size of the lesion necessarily that dictates the pain associated.” Onset of pain can be delayed, and might appear 6 months after the initial injury. This occurs because when the nervous system is injured, its reorganization may go well or may go poorly during the re-wiring process. Using the analogy of a short-circuited wire, individuals may have central pain after a stroke or nerve injury but may have delayed pain; this can occur up to a year later.
Some of the agents that are used to treat CNS pain are botulinum toxin A and B, baclofen, tizanidine, and gabapentin. Gabapentin is not yet approved for CNS pain but its two formulations have been helpful for some patients. Dr. Argoff added that 300 to 400 patients at their regional center are receiving intranasal baclofen, but relieving spasticity alone does not stop their pain. Some patients may have pain because it is not one of the hallmarks of the illness, may not be asked about it. For example, 80–90% of stroke patients experience delayed pain, but may not be asked about it or tested for it. With movement disorders it is important to ask patients how comfortable they are.
As for use of the opioids, Dr. Arnoff noted that they usually produce inconsistent results, some positive and some negative. No single study supports their use beyond a short period. Also, intravenous lidocaine infusions provide only temporary relief, and then only in the skin.
When a spinal cord injury occurs above the thoracic region there is a greater chance of spasticity and this is where intraspinal baclofen may be most useful, he said. For patients with multiple sclerosis, baclofen and the non-opioid non-NSAID agent ziconatide may be useful, but again he stressed there is not yet enough hard data to prove this. Deep brain stimulation has been helpful for post-stroke patients, but monitoring and follow-up are crucial, Dr. Arnoff added.
The overall message for clinicians is to ask patients about their pain, and to listen to their description of it. The complexities of the CNS make it easy to misdiagnose the source of pain. As in MS patients and those with Parkinson's disease, it is essential to remember that chronic and sometimes puzzling pain with no apparent connection to the CNS is actually a part of the disease.