Motor Cortex Stimulation for Intractable Pain

Richard K. Osenbach, M.D.


Neurosurg Focus. 2006;21(6) 

In This Article

Pharmacological Classification of Pain

The outcome of pharmacological testing has been used to provide a rational basis for implementing various treatment modalities, including medications, therapeutic injections, and surgical procedures.[14] For example, pain relief in response to intravenously administered lidocaine may provide a rational basis for a trial of oral mexilitene. Similarly, a positive response to a drug such as phentolamine might suggest the presence of a component of sympathetically maintained pain that might be effectively treated with repetitive chemically induced sympathetic blockade or with a sympathectomy. The potential benefit of pharmacological testing in predicting the result of a given surgical treatment is particularly attractive because surgical procedures such as MCS can be time-consuming, are costly, and are associated with a finite set of risks.

There is evidence to suggest that certain excitatory amino acids such as glutamate play a critical role in hyperactivity states that occur after deafferentation, and the NMDA receptor is believed to play a central role in sustaining nociceptive transmission, particularly after deafferentation. It has been shown that competitive or noncompetitive NMDA receptor antagonists can reduce these hyperactive states, both in the spinal cord and in the cerebral cortex. Ketamine is a noncompetitive NMDA receptor antagonist that has been used for many years as an anesthetic agent. Ketamine also has well-recognized analgesic properties at subanesthetic doses, and it has been suggested that these analgesic effects are also mediated at the NMDA receptor site, particularly in deafferentation.

Barbiturates have also been shown to be effective in some patients with deafferentation pain. The analgesic effects of barbiturates probably occur through multiple mechanisms of antinociception, including membrane stabilization, inhibition of excitatory neurotransmitter release, suppression of calcium channels, lowering of postsynaptic receptor-mediated responses to excitatory amino acids, interference with intracellular second messengers, depression of sodium channels, and enhancement of the γ-aminobutyric acid neurotransmission. Some of the ultrashort-acting barbiturates have been reported to be successful in blocking the effects of excitatory amino acids in synaptic transmission.

Morphine is an opioid agonist that has traditionally been believed to be ineffective for the treatment of neuropathic pain in general and deafferentation pain in particular. Morphine is most effective for nociceptive pain that is generated by the activation of peripheral nociceptors, a situation that is quite different from that encountered in central pain syndromes. Unfortunately, it is often difficult to identify the exact cause of intractable pain, and in some patients components of both deafferentation and nociceptive pain certainly coexist. It is not entirely clear why morphine is effective in some cases of central pain, although it is likely that fairly complex mechanisms are involved.

To predict which patients might respond favorably to MCS, at my institution we have adopted a preoperative intravenous infusion protocol for pharmacological classification of pain that is similar to a protocol published previously.[34] All patients selected for MCS undergo testing with intravenously delivered morphine, thiopental, and ketamine according to a standardized protocol ( Table 2 ). The testing is usually performed over 2 days on an outpatient basis by an anesthesiologist. Standard procedures to monitor heart rate, blood pressure, respiration, oxygen saturation, and level of sedation are performed in all patients. At the beginning of each test, saline is injected before the active drug to identify and characterize the magnitude of any potential placebo effect. The baseline pain level is assessed using the VAS, the patient is then asked to rate his or her pain every 5 minutes during the infusion, and the results are then plotted. The level of consciousness is carefully monitored to ensure that reductions in pain reported by the patient in fact represent true analgesia and are not related to a sedative effect of the drug being infused. The development of any psychological reaction during testing, such as hallucinations (more common with ketamine), is carefully noted. Only reliable pain scores recorded before the onset of these side effects are used for judging the level of pain. A 40% reduction in the VAS score from baseline is considered to be significant, and if this occurs the pain is classified as sensitive to that particular agent.

Yamamoto et al.[34] used intravenous infusions of morphine, barbiturate (thiamylal), and ketamine in an attempt to clarify the neuropharmacological characteristics of central poststroke pain and to correlate these results with the effectiveness of MCS. In their series of patients with central poststroke pain, eight (20.5%) of 39 responded positively to morphine, 22 (56.4%) of 39 were sensitive to thiamylal (an ultrashort-acting barbiturate), and 11 (47.8%) of 23 patients were sensitive to ketamine. The authors combined the data and classified the results of pharmacological testing into four categories according to sensitivity ( Table 3 ). No obvious differences in pharmacological characteristics were noted between patients with thalamic and suprathalamic pain. Twenty-eight (72%) of 39 patients underwent long-term MCS. The best results were obtained in patients who demonstrated a positive response to either barbiturate or ketamine but not to morphine. Ten (71%) of 14 patients with Type II pain responded favorably to MCS, whereas two (50%) of four with Type I pain responded favorably. Combining patients with Type I and Type II pain, 12 (67%) of 18 benefited from MCS. In contrast, MCS was effective in only one (10%) of 10 patients whose pain was classified as Type III or IV according to pharmacological testing. Regression analysis comparing the magnitude of the response to each drug in each patient with the magnitude of pain relief obtained using MCS revealed a significant correlation with thiamylal and ketamine but showed no significant correlation with morphine.


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