The efficacy of the AMPA receptor antagonist NS1209 and lidocaine in nerve injury pain: a randomized, double-blind, placebo-controlled, three-way crossover study

Lise Gormsen, Nanna B Finnerup, Per M Almqvist, Troels S Jensen
Anesthesia and Analgesia 2009, 108 (4): 1311-9

BACKGROUND: Chronic neuropathic pain is inadequately treated using current therapies, with less than half of patients achieving clinically significant pain relief (defined as more than 50% pain reduction). In this study, we evaluated the AMPA/GluR5 receptor antagonist NS1209 for efficacy, safety, and tolerability in comparison with placebo and lidocaine for the treatment of chronic neuropathic pain and allodynia in patients with peripheral nerve injury.

METHODS: A randomized, double-blind, placebo-controlled, three-way crossover study was designed to recruit patients with chronic neuropathic pain for IV treatment with NS1209 (322 mg), lidocaine (5 mg/kg), and placebo. Measures of spontaneous current pain and pain evoked by brush, pinprick, cold, and heat stimulation were performed at screening and at 0, 2, 4, 6, 8, and 24 h after the start of the treatment session.

RESULTS: Thirteen patients completed the study. Neither NS1209 nor lidocaine showed a statistically significant effect over placebo on the primary end-point spontaneous current pain, but both compounds exhibited a statistically significant effect on the secondary end-point pain relief of overall spontaneous pain compared with placebo. Similar to lidocaine, NS1209 was superior to placebo in alleviating some key symptoms of neuropathic pain, i.e., evoked types of pain, including mechanical and cold allodynia.

CONCLUSIONS: These findings are consistent with those reported for NS1209 in other models of pain and suggest that there is a role for AMPA receptor involvement in neuropathic pain in humans. Furthermore, NS1209 was safe and well tolerated at the given doses with a safety profile similar to placebo.

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