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Anesth Analg 2004;98:1581-1584 © 2004 International Anesthesia Research Society doi: 10.1213/01.ANE.0000113258.31039.C8
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Abstract |
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Functional neuroimaging suggests that similar brain regions are involved in the processing of pain in healthy subjects and in patients with chronic neuropathic central pain. We present a patient with chronic neuropathic central pain due to a unique lesion to the trigeminal and spinothalamic pathway who had persistent pain relief after repeated IV lidocaine infusions. Positron emission tomography scan results showed a relative hypoactivity of the left posterolateral thalamus before treatment which disappeared after therapy. This case may suggest a stereo-selective analgesic effect of lidocaine accompanied by regional cerebral blood flow changes in the thalamus, indicating that sodium channels could, in fact, be highly expressed or modified in the thalamus after thalamic deafferentation.
IMPLICATIONS: We present a case of persistent central pain after encephalitis in a patient who had long-term pain relief after a series of IV lidocaine infusions. A positron emission tomography scan study, done before and after treatment, suggested that lidocaine for the diagnosis of chronic neuropathic pain may have a specific site of action in the brain.
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Introduction |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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Functional neuroimaging (1–3) and electroencephalographic/magnetoencephalographic mapping studies on healthy subjects (4) suggest the role of the cingulate gyrus, insula, dorsolateral frontal cortex, secondary somatosensory cortex, inferior parietal lobe, cerebellum, and lateral thalamus in central pain processing. The same brain regions appear to also be involved in the pathogenesis of chronic neuropathic central pain (CNCP) (2,5), but the exact role of each area is poorly understood. Thus, not surprisingly, the treatment of CNCP remains a particularly challenging task.
The antiallodynic and antihyperalgesic effects of systemic lidocaine have been demonstrated in neuropathic pain models in rats (6), in healthy subjects with provoked pain (7,8), and in patients with peripheral as well as central nervous system (CNS) injury (9). Thus, IV lidocaine may be an alternative therapy in refractory CNCP due to CNS damage (10). However, it is unclear whether lidocaine, a sodium channel blocker (11), exerts its effect on specific brain regions.
We present a patient with CNCP due to a unique lesion of the spinothalamic pathway who had persistent pain relief after a repeated series of IV lidocaine infusions. On the basis of positron emission tomography (PET) scan results, we discuss the possible mechanisms and action site of lidocaine in CNCP.
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Case Report |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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A 67-yr-old, 54-kg woman, in general good health, was referred to our pain center complaining of a burning pain sensation on the left side of her body, including the lower left face. This symptom had started in 1998, 2 wk after a Listeria rhomboencephalitis, diagnosed by a positive polymerase chain reaction test in the cerebrospinal fluid to Listeria monocytogenes. Magnetic resonance imaging showed a lesion in the left pontine tegmentum (Fig. 1) involving the spinal-trigeminal tract and nucleus, as well as a facial nerve lesion slightly extending to the right side.
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The patient complained of "hot" left-sided paraesthesias and burning pain of an intensity of 80 of 100 mm on the visual analog scale (VAS) and maximal (100-mm) pain on the chin and the left palm that was aggravated by fatigue and touch. Pain attacks (lancinating and shooting pains) occurred at a frequency of >30 episodes a day.
Neurological examination revealed left trigeminal hypoesthesia and fascicular facial palsy; left body sensory loss to touch, pain, and temperature, which was most severe at the hand; and mechanical and thermal hyperalgesia and allodynia. Normal somatosensory evoked potential latencies confirmed the integrity of the lemniscal pathway, and the electroneuromyographic study excluded noncentral causes of pain (such as peripheral neuropathy). A standardized psychiatric interview and cognitive examination were normal except for the presence of a moderate depressive state (global depression scale score of 28).
The pain remained nonresponsive to treatment with numerous drugs, such as amitriptyline, nortriptyline, carbamazepine, oxcarbazepine, gabapentin, sodium valproate, lamotrigine, baclofen, and clonazepam. At this point, IV lidocaine was contemplated, and all oral drugs were discontinued 3 wk before the beginning of treatment to allow washout. The patient’s symptoms did not worsen, and she gave informed consent for the therapy and the imaging studies.
Two cycles of daily IV lidocaine (Astra-Zeneca, Zug, Switzerland) infusions (5 mg/kg diluted in 150 mL of 0.9% NaCl over 30 min without a bolus) for 5 days were arbitrarily chosen and performed at a 6-mo interval. Hemodynamic variables (heart rate, oxygen saturation, respiratory rate, arterial blood pressure, and three-lead electrocardiogram) were continuously monitored during the infusion while one of the authors was present to assess and treat any adverse effects. Mild somnolence and cognitive slowing during the infusion period and up to the following 6 h were the only side effects noted. None of the treatments was interrupted because of lidocaine toxicity.
Spontaneous pain was assessed by using the 100-mm VAS, and evoked pain was measured by brushing (three brush strokes) obtained before and 6 h after the completion of the infusion. Persistent spontaneous pain reduction was observed immediately after treatment (Day 0); 1, 3, and 7 days after treatment; and 1, 2, and 3 mo after treatment (Fig. 2) in all body areas but the chin. The frequency of pain attacks significantly diminished as well (Fig. 3). Although this was not quantified, hyperalgesia and allodynia evoked by external stimulation decreased in the same proportion as spontaneous pain. The depressive state did not change. The second treatment course 6 mo later produced similar results.
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The procedure, which was similar for both acquisitions, involved repetitive touch stimuli delivered by one of the author’s fingers to the left allodynic palm. The patient was scanned once 24 h before the first lidocaine infusion and was scanned the second time 24 h after the final infusion. Both scans were performed during the second lidocaine course in a quiet room at a constant ambient temperature of 22°C. The stimulation was begun 60 s after IV injection of the tracer. Stimulation time was 40 s every minute for 20 min, to avoid sensitization and habituation.
The emission study started 30 min after IV injection of 222 MBq of [18F]fluorodeoxyglucose. PET scans were obtained on the ECAT ART tomograph (CTI/Siemens, Knoxville, TN). Images were reconstructed by using an analytic three-dimensional reprojection algorithm (12,13) after a model-based scatter correction was applied. The default variables used were ramp filter cutoff at a frequency of 0.35 cycles per pixel and reconstructed images of 47 slices with 128 x 128 resolution (voxel size = 3.4 x 3.4 x 3.4 mm3).
Thalamic, parietal, and cerebellar stimulation-induced activity was qualitatively compared before and after therapy. Results showed a relative hypoactivity of the left posterolateral thalamus before the lidocaine infusion; this disappeared after therapy (Figs. 4 and 5).
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Discussion |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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The incidence of central pain secondary to CNS disease, specifically encephalitis, remains unknown. It is characterized by the presence of spontaneous burning pain, as well as evoked allodynia and hyperalgesia. Single IV lidocaine infusions offer moderate yet transient analgesic effects (14). We hypothesized that repeated IV lidocaine infusions would provide superior and long-lasting analgesia by reducing the chronic sensitization state present in central pain and that this effect might be stereospecific.
Our patient had refractory CNCP due to a single lesion of the trigeminal and spinothalamic pathways and demonstrated persistent analgesia with repeated cycles of daily IV lidocaine infusions. Because of this prolonged response, oral lidocaine treatment was not sought. Such a protocol has never been tested in humans and may be responsible for the prolonged analgesia observed in the various body regions (4–12 weeks). Continuous systemic infusions of lidocaine have provided analgesia in animal models of neuropathic pain (15). Although cardiac and neurological toxicity was not found in this patient, the potential for major cardiovascular and neurological events (e.g., arrhythmias and convulsions) is present, and the authors stress the importance of performing this protocol under vigilant monitoring.
Another interesting finding is that the PET scan suggested a selective action of the IV lidocaine on the ipsilesional thalamus in a palm stimulation condition; this disappeared after lidocaine infusion. This result is in line with previous case reports that demonstrated asymmetric regional cerebral blood flow (rCBF) in the thalamus in patients with continuing pain due to either peripheral neuropathic pain (16,17) or central pain caused by cortical lesions sparing the thalamus (18). This abnormal thalamic activity was reduced by anesthetic blocks in the case of peripheral neuropathic pain (16) or by motor cortex stimulation in case of central pain (18,19). The role of the thalamus in the persistence of CNCP has also been described in patients after spinal cord injury and deafferentation, where spontaneous neuronal hyperactivity of thalamic cell groups has been registered (20). It has also been hypothesized that allodynic stimuli modify contralateral rCBF in the thalamus of CNCP patients with bulbar lesions (5).
Regional CBF changes in the thalamus, as seen in pain imaging studies, are considered to reflect a general arousal reaction to the presence of pain (21), whereas the frontal, insular, parietal, and cingulate areas are primarily involved in the cognitive, discriminative, perceptive, and emotional aspects of pain processing. If the effect of lidocaine is selective on the thalamus and the arousal component of pain, we should not expect any change in the emotional response to pain. Indeed, in this case, the patient’s depressive state did not improve despite pain reduction. It is possible that lidocaine influenced rCBF by inhibiting platelet aggregation (22); however, its stereospecific effects on the posterolateral thalamus remain unexplained.
The analgesic properties of lidocaine are probably mediated by changes in brain sodium channels (11), but very little is known about sodium channel brain expression in CNCP. Our case may suggest a stereoselective analgesic effect of lidocaine witnessed by rCBF changes in the thalamus, indicating that sodium channels could, in fact, be highly expressed or modified in the thalamus after thalamic deafferentation.
The precise biological nature of sodium channel expression remains unclear. Further studies comparing repeated lidocaine versus single lidocaine versus placebo infusions are needed to assess the long-term efficacy of these treatments. However, this case illustrates that certain brain regions—namely, the posterolateral thalamus—involved in the experience of pain are specifically and repeatedly responsive to IV lidocaine.
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