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Ketamine Clinical Trials

Pregabalin in Patients with Central neuropathic pain: A randomized, double-blind, placebo-controlled trial of a flexible-dose regimen.

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Id: NTR852

Organisation Name: Academic Medical Center, Amsterdam Department of anesthesiology Pain Relief Unit

Overal Status: Inclusion stopped, follow up

Start Date: 2006-01-01

Lead Sponsor: Academic Medical Center, Amsterdam Department of anesthesiology Pain Relief Unit

Brief Summary: Central neuropathic pain (pain associated with lesions of the central nervous system) has been estimated to occur in up to 8% of patients after a stroke, and about 10% to 30% of patients with spinal cord injury are affected during the course of their illness.
(1)The mechanisms underlying central neuropathic pain are not completely understood. A dominating feature of central pain, however, is an abnormal spinothalamic function with altered sensitivity to temperature and pinprick.
(2) Disruption of the spinothalamic pathways may contribute to neuronal hyperexcitability, loss of descending inhibitory control mechanisms in the spinal cord, and alterations in the processing of incoming noxious and non-noxious stimuli resulting in an abnormal pain perception (1, 3). In addition, loss of balance between noxious and non-noxious sensory inputs gives rise to neuronal reorganization in the thalamus contributing to the onward flow of nociceptive information to the postcentral gyrus of the cortex (4). Despite recent advances in identification of peripheral and central sensitization mechanisms related to central nervous system injury, the effective treatment of patients suffering from central pain remains a clinical challenge. Nevertheless the numerous treatment options available (including opioids, anticonvulsants, antidepressant, baclofen, á-adrenergic agonists, and ketamine), some of these patients still experience severe neuropathic pain. In addition, the use of these agents is often limited by significant side effects.

Recently, pregabalin was reported to possess antihyperalgesic and antiallodynic properties in a wide range of animal models, and to be effective in randomized clinical trials of nonmalignant chronic neuropathic pain (including postherpetic neuralgia and diabetic peripheral neuropathy). (5, 6, 7) Additionally, this anticonvulsant has excellent bioavailability and a favorable safety profile with minimal concern for drug interactions and no interference with hepatic enzymes. The exact mechanism of action of pregabalin is unclear. Although structurally related to gamma-aminobutyric acid (GABA), pregabalin is inactive at GABAA and GABAB receptors and it does not alter GABA uptake or degradation. Pregabalin (like gabapentin), however, binds with high affinity to the á2-ä protein (subtype 1 and 2) (situated in various regions of the brain and in the superficial dorsal horn), an auxiliary protein of (presynaptic) voltage-gated N-type calcium channels in stimulated neurons. (7-9) Voltage- gated calcium channels in the central nervous system provide rapid and fine-tuned modulation of neurotransmitter release by controlling fusion of synaptic vesicles to presynaptic membranes. (10) Their blockade by pregabalin reduces the calcium influx at nerve terminals (preventing synaptic vesicles from fusing) and hence reduces the release of several neurotransmittors including glutamate, norepinephrine, gene-related peptide, and substance P that are particularly relevant for potential neuronal hyperexcitability. (11, 12).

Although recent trials confirm the effectiveness of pregabalin in peripheral neuropathic pain, the role of pregabalin in the treatment of central neuropathic pain remains unknown. Given the absence of other effective pharmacological treatments for central pain, any medication providing some benefits in terms of symptom amelioration and quality of life improvement in patients with neuropathic pain have to be evaluated.

Country: Netherlands

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