Vincenzo Bonicalzi

Therapeutic extradural cortical stimulation for central and neuropathic pain: a review.

ObjectiveExtradural cortical stimulation is a recent addition to the armamentarium of functional neurosurgery. This article reviews results of treatment of chronic central and neuropathic pain. ConclusionsIt is concluded that extradural cortical stimulation may be effective in several refractory cases.

The neurochemistry of central pain: evidence from clinical studies, hypothesis and therapeutic implications.

&NA; Recent evidence suggests that central pain, i.e., pain due to central nervous system damage, may be due to a deranged neurotransmission between the sensory thalamus and sensory cortical areas. Central pain can be controlled either by opposing glutamate neurotransmission or potentiating GABAergic transmission. It is speculated that a relative hypofunction of the GABAergic inhibition both at thalamic and cortical levels leads to a sectorial excitatory hypertonus in those same areas. A blend of the two should mark each patient. A pharmacological dissection approach is provided that should optimize the treatment, up to now globally poor, of central pain.

Lamotrigine control of central pain.

Central pain remains a therapeutic challenge. We report beneficial effects of lamotrigine, a novel antiepileptic drug, on four patients suffering from long-standing central pain. Analgesia may be due to interference with glutamatergic transmission.

Therapeutic extradural cortical stimulation for movement disorders: A review

Abstract Extradural motor cortex stimulation was introduced in 1989 for control of central pain. In recent years this has been found useful in several patients with movement disorders. This paper attempts to bring together all the relevant literature, discuss mechanisms and lay out guidelines for future research and clinical applications.

Propofol analgesia in central pain: Preliminary clinical observations

Propofol, an intravenous general anaesthetic, has been reported to relieve some forms of pruritus at subhypnotic doses. We assessed its effectiveness in 32 patients with several kinds of non-malignant chronic pain, in a placebo-controlled, double-blind study. We found that central pain, but not neuropathic pain, is at least partially controlled by propofol at subhypnotic doses, without major side-effects. In particular, allodynia associated with central, but no neuropathic, pain has been completely controlled. Propofol analgesia leads to renormalization of brain metabolism as seen on single photon emission computed tomography. We conclude that propofol may help in the diagnosis of central pain, particularly in unclear cases, and also in treatment. Possible mechanisms of action are discussed.

Lamotrigine control of trigeminal neuralgia: an expanded study.

Sirs: We examined the effect of lamotrigine, a novel antiepileptic drug, on trigeminal neuralgia. The initial results in 4 patients have been reported [1]. A consecutive series of 21 patients suffering from idiopathic trigeminal neuralgia (ITN) was enrolled if a previous trial of carbamazepine has been ineffective, partially effective or with side effects; one patient had declined the carbamazepine trial. Informed consent was given by all subjects. The series consisted of 14 women and 7 men, with a mean age of 65 years (range: 31–81). Pain was referred to one trigeminal branch in 11 cases (III: 6; II: 4; I:1), to two in 8 cases (II-III: 4; I-II: 4) and to three in 2 cases. Twelve patients complained of pain on the right side and 9 on the left. Seventeen patients had received no previous surgery for their pain, three had previously undergone Fogarty balloon compression and one decompression in the posterior fossa, with relapse. Twenty patients had received carbamazepine up to analgesia or had had side effects (range: 200–1200 mg; mean: 726 mg; median: 600 mg). Lamotrigine was started at a dose of 50 mg daily and rapidly titrated to effect. Carbamazepine had been administered to 20 patients; it was effective in 12 cases, partially effective in 6 cases and ineffective in 2 cases of ITN. The first 12 cases plus another with partial relief developed side effects of moderate-to-severe degree. Lamotrigine (Lamictal, GlaxoWellcome), at a mean dosage of 362 mg (median: 400 mg; range: 150– 600 mg), in divided doses, achieved 100% pain relief in 7 patients, almost complete relief (i.e., slight and/ or occasional attacks in 7 patients), partial control (patient improved, though incompletely satisfied) in 3 patients and no relief in 4 patients with ITN. Side effects included: skin rash, 4 cases; sedation with dosage greater than 200 mg, 1 case, confusion plus vertigo, 1 case. In the first 4 cases, lamotrigine was suspended without relapse, suspended with return to carbamazepine, suspended with ensuing surgery or continued without ill effects. The patient who developed confusion plus vertigo was operated on. Two patients, one with excellent and another with partial relief, went on to surgery owing to the cost of therapy or refusal of drug dependency at 150 mg t.i.d. In all cases of lamotrigine ineffectiveness, carbamazepine was either effective with side effects (3 cases) or partially effective (1 case). In 2 cases of carbamazepine insensitivity, lamotrigine was either almost totally or partially effective. Follow-up for ITN patients is now 7.1 months (mean; median 6 months; range: 1–15 months). We also administered lamotrigine to a 46-year-old man suffering from trigeminal neuralgia due to multiple sclerosis and a 78-year-old woman suffering trigeminal neuralgia due to a vestibular schwannoma. The former patient had no benefit from carbamazepine (1200 mg), but was 100% controlled by lamotrigine 150 mg t.i.d. (follow-up: 6 months); skin rash developed, but was controlled by terfenadine, an antihistaminic drug, without discontinuing lamotrigine. The latter patient was controlled by carbamazepine (600 mg) with side effects and was almost 100% relieved by lamotrigine, 150 mg (follow-up: 1 month). Carbamazepine is considered the drug of choice for trigeminal neuralgia: it is effective initially in 75% of patients, but up to 33% cannot tolerate the drug in the doses required to alleviate the pain [3]. In this series, lamotrigine was effective in 81% of ITN patients (95% C.I. 58–95) and 82% globally (95% C.I. 61–95). If we exclude the patient who declined the carbamazepine trial, lamotrigine was effective in 80% of ITN patients. Side effects were seen in 30% af all patients (21% skin rash plus 9% others). The high incidence of skin rash in this series runs counter to that reported in the literature, i.e., 2–3% [2], almost certainly due to the fast titration to effect in our study. However, in 2 of the 5 cases of skin rash, there was no need to discontinue treatment, reducing the clinically significant skin rash to 13%. In sum, lamotrigine is a valuable new addition to drugs effective on trigeminal neuralgia. A formal randomized placebo-controlled study in now indicated.

Lamotrigine reduces total postoperative analgesic requirement: A randomized double-blind, placebo-controlled pilot study

BACKGROUND Postoperative pain is undertreated. Lamotrigine, a new antiepileptic drug, has analgesic properties in its antisodium and antiglutamatergic effects. It may prevent postoperative pain. This pilot study assessed lamotrigine effects on postoperative pain. METHODS This was a double-blind, randomized, placebo-controlled pilot study of 30 patients submitted to transurethral prostatectomy under spinal anesthesia and receiving 200 mg of lamotrigine 1 hour before spinal anesthesia. RESULTS We observed a statistically significant reduction in total analgesic assumption (p < 0.01) and in visual analog scale scores at 2 (p = 0.04), 4 (p < 0.01), and 6 (p = 0.04) hours after operation. CONCLUSIONS Lamotrigine may be an effective means of reducing postoperative pain.

Low-rate repetitive TMS allays central pain.

Abstract Only about 50% of central pain patients respond to motor cortex stimulation in the long run. There is a need for prognostic factors. Here we show that propofol test and TMS both predict short-term effect in nine patients with central pain. This may help reduce the number of failures.

Drug therapy of trigeminal neuralgia.

Trigeminal neuralgia is a chronic pain syndrome of still unestablished origin. Its diagnosis depends on clinical grounds. Drug therapy initially helps a great majority of patients. The choice of drugs is quite large, but truly effective compounds with a tolerable side effect profile remain few. Carbamazepine (or oxcarbazepine) and lamotrigine appear to be the most effective, followed by baclofen. Several patients require further nonpharmacological treatment for which no evidence-based recommendation is possible. In the future, neuromodulation may be brought to bear, as in other chronic pain syndromes.

The Role of Cortex in Central Pain Syndromes

The role of the somatosensory cortex in central pain syndromes is widely questioned. Two recent position emission tomography studies detected a strong activation of the parietal and cingular cortices after brief nociceptive stimuli. On the other hand, a recent single photon emission computed tomography study found no cortical activation in five patients affected by central poststroke pain and algodystrophia. In this study, we present the single photon emission computed tomography findings in five patients suffering from central pain syndromes. Two of these, one with facial postrhizotomy anesthesia dolorosa and the other with central poststroke pain, showed a decrease of blood flow in the parietal lobe, further decreasing after stimulation by nonpainful maneuvers. Our results suggest that somatosensory cortical areas might be involved in the generation of anomalous pain states in some cases of central pain syndromes.