United States Patent 1 Mayer et al. [54] METHOD FOR THE TREATMENT OF CHRONIC PAIN Inventors: David J. Mayer; Donald D. Price; Jianren Mao, all of Richmond, Va; John W. Lyle, Belmar, N.J. Virginia Commonwealth University ‘Medical College of Virginia, Richmond, Va. 5) [73] Assignee: Ri) 22) [51] {52] [58] [56] Appl. No. Filed: Int, CL US. G. Field of Search References Cited U.S. PATENT DOCUMENTS 4316888 2/1982 $02,908 7/1986 476,372 9/1988 4785,000 11/1988 41876276 10/1989 4994467 2/1991 5,006,510 4/1991 5013,540 5/1991 5,023,239 6/1991 5,055,481 10/1991 5.068.228 11/1991 5.126330 6/1992 OTHER PUBLICATIONS Hayes et al., “Pretreatment with gangiolsides reduces 2,477 ‘Mar. 5, 1993 sonenee AOUK 31/485 -- 514/289; $14/647 514/289, 647 Nelson silk eta Kreek Kreek Mechoulam et al. ‘Zimmerman Ellis Redbura Ogura etal TInukai et a. Kohler Ogura et al. 247 514/284 aari0 AQT AAA "USON53526834 Patent Number: 5,352,683 Oct, 4, 1994 Date of Patent: (1) [45] abnormal nociceptive responses associated with a ro- dent peripheral mononeuropathy”, Pain, 48 (1992) 391-396. ‘Mao et al., “Post-injury treatment with GMI ganglio- side reduces nociceptive behaviors and spinal cord met- abolic activity in rats experimental peripheral mononeuropathy”, Brain Research, 584 (1992) 18-27. Mao et al., “Intrathecal GMI ganglioside and local nerve anesthesia reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy”, Brain Research, 584 (1992) 28-35, ‘Mao et al. “Pain-related increases in spinal cord mem- brane-bound protein kinase C following peripheral nerve injury”, Brain Research, 588 (1992) 144-149. Mao et al., Brain Research, $76 (1992) 254-262. Primary Examiner~Marianne M. Cintins Assistant Examiner—William R. A. Jarvis Attorney, Agent, or Firm—Dilworth & Barrese (7) ABSTRACT ‘Chronic pain is alleviated in a mammal suffering there- from by administering to the mammal a chronic pain alleviating amount of a nontoxic N-methyl-D-aspartate receptor antagonist such as dextromethorphan, dextror- phan, ketamine or pharmaceutically acceptable salt thereof, alone or in combination with a local anesthetic ‘and optionally in sustained release dosage form. 9 Claims, 4 Drawing SheetsUSS. Patent Oct. 4, 1994 Sheet 1 of 4 5,352,683 12.5 nmol 25 nmol 100 nmol w i a = a 3 — & o Es. 8 S ttt bo z Q e < 9 | 5 = eu 2 z O c= = le a L c < on > < ba o ro HYPERALGESIA: (DIFF. SCORE IN SEC)US. Patent Oct, 4, 1994 Sheet 2 of 4 5,352,683 12.5 nmol 100 nmol 10 50 nmol —— — =e DAYS AFTER NERVE LIGATION FIG.2 HYPERALGESIA: (DIFF. SCORE IN SEC)