Effect of NMDA NR2B antagonist on neuropathic pain in two spinal cord injury models

• Published in: Pain (Amsterdam) Vol. 153; no. 5; pp. 1022 - 1029
• Main Authors: Kim, Youngkyung, Cho, Hwi-young, Ahn, Young Ju, Kim, Junesun, Yoon, Young Wook
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier B.V 01.05.2012; Elsevier
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Amino Acid Antagonists - therapeutic use; Fundamental and applied biological sciences. Psychology; Illness and personality; Illness, stress and coping; Male; Medical sciences; Nervous system (semeiology, syndromes); Neuralgia - drug therapy; Neuralgia - etiology; Neuralgia - metabolism; Neurology; Neuropathic pain; NMDA NR2B; NR2B antagonists; Pain Measurement - drug effects; Phenols - pharmacology; Phenols - therapeutic use; Piperidines - pharmacology; Piperidines - therapeutic use; Psychology and medicine; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord Injuries - complications; Spinal Cord Injuries - metabolism; Spinal cord injury; NR2B antagonists; Spinal cord injury; NMDA NR2B; Neuropathic pain; Spinal cord; Pathogenesis; Central nervous system; Aspartate; Glutamate receptor; Pain; Excitatory aminoacid; Neurotransmitter; Models; Sensitization; NMDA receptor; Subtype
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/j.pain.2012.02.003

NR2B antagonists increased the mechanical nociceptive threshold after 2 experimental spinal cord injury models with no motor depression, and NR2B expression was increased in the spinal cord. N-Methyl-d-aspartate (NMDA) receptors are thought to play an important role in the processes of central sensitization and pathogenesis of neuropathic pain, particularly after spinal cord injury (SCI). NMDA antagonists effectively reduce neuropathic pain, but serious side effects prevent their use as therapeutic drugs. NMDA NR2B antagonists have been reported to effectively reduce inflammatory and neuropathic pain. In this study, we investigated the effects of NR2B antagonists on neuropathic pain and the expression of NR2B in the spinal cord in 2 SCI models. SCI was induced at T12 by a New York University impactor (contusion) or by sectioning of the lateral half of the spinal cord (hemisection). Ifenprodil (100, 200, 500, 1000nmol) and Ro25-6981 (20, 50, 100, 200nmol) were intrathecally injected and behavioral tests were conducted. Ifenprodil increased the paw withdrawal threshold in both models but also produced mild motor depression at higher doses. Ro25-6981 increased the mechanical nociceptive threshold in a dose-dependent manner without motor depression. NR2B expression was significantly increased on both sides at the spinal segments of L1–2 and L4–5 in the hemisection model but did not change in the contusion model. Increased expression of NR2B in the hemisection model was reduced by intrathecal ifenprodil. These results suggest that intrathecal NMDA NR2B antagonist increased the mechanical nociceptive threshold after SCI without motor depression. A selective subtype of NMDA receptor, such as NR2B, may be a more selective target for pain control because NMDA receptors play a crucial role in the development and maintenance of chronic pain.