Effects of gabapentin on brain hyperactivity related to pain and sleep disturbance under a neuropathic pain-like state using fMRI and brain wave analysis

• Published in: Synapse (New York, N.Y.) N.Y.), 2011-07, Vol.65 (7), p.668-676
• Main Authors: Takemura, Yoshinori, Yamashita, Akira, Horiuchi, Hiroshi, Furuya, Masaharu, Yanase, Makoto, Niikura, Keiichi, Imai, Satoshi, Hatakeyama, Noboru, Kinoshita, Hiroyuki, Tsukiyama, Yoshi, Senba, Emiko, Matoba, Motohiro, Kuzumaki, Naoko, Yamazaki, Mitsuaki, Suzuki, Tsutomu, Narita, Minoru
• Format: Article
• Language: English
• Subjects: Amines - pharmacology; Analgesics - pharmacology; Animal models; Animals; Axotomy; Brain - drug effects; Brain mapping; Brain Mapping - methods; Brain Waves - drug effects; chronic pain; Computed tomography; Cyclohexanecarboxylic Acids - pharmacology; EEG; EMG; Eye; fMRI; Functional magnetic resonance imaging; gabapentin; gamma-Aminobutyric Acid - pharmacology; Hyperactivity; Magnetic Resonance Imaging; Magnetoencephalography; Male; Mice; Mice, Inbred C57BL; Neuralgia - complications; Neuralgia - drug therapy; neuropathic pain; Neuropathy; Pain; Pain Measurement - methods; Sciatic nerve; Sciatic Nerve - injuries; Sciatic Nerve - physiology; Sleep (NREM); Sleep and wakefulness; Sleep disorders; Sleep Wake Disorders - etiology; Sleep Wake Disorders - physiopathology; Statistical analysis; Synapses
• ISSN: 0887-4476; 1098-2396; 1098-2396
• DOI: 10.1002/syn.20898

Neuropathic pain is the most difficult pain to manage in the pain clinic, and sleep problems are common among patients with chronic pain including neuropathic pain. In the present study, we tried to visualize the intensity of pain by assessing neuronal activity and investigated sleep disturbance under a neuropathic pain‐like state in mice using functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG)/electromyogram (EMG), respectively. Furthermore, we investigated the effect of gabapentin (GBP) on these phenomena. In a model of neuropathic pain, sciatic nerve ligation caused a marked decrease in the latency of paw withdrawal in response to a thermal stimulus only on the ipsilateral side. Under this condition, fMRI showed that sciatic nerve ligation produced a significant increase in the blood oxygenation level‐dependent (BOLD) signal intensity in the pain matrix, which was significantly decreased 2 h after the i.p. injection of GBP. Based on the results of an EEG/EMG analysis, sciatic nerve‐ligated animals showed a statistically significant increase in wakefulness and a decrease in nonrapid eye movement (NREM) sleep during the light phase, and the sleep disturbance was almost completely alleviated by a higher dose of GBP in nerve‐ligated mice. These findings suggest that neuropathic pain associated with sleep disturbance can be objectively assessed by fMRI and EEG/EMG analysis in animal models. Furthermore, GBP may improve the quality of sleep as well as control pain in patients with neuropathic pain. Synapse 2011. © 2010 Wiley‐Liss, Inc.