Subdiaphragmatic vagotomy promotes nociceptive sensitivity of deep tissue in rats.
To verify whether vagal dysfunction is associated with chronic pain, we evaluated the effects of subdiaphragmatic vagotomy (vgx) on the sensitivity toward noxious stimuli in rats. Vgx rats showed sustained hyperalgesia in the gastrocnemius muscle without tissue damage (no increase in vgx-induced plasma creatine phosphokinase or lactose dehydrogenase levels) accompanied by hypersensitivity to colonic distension. We found a dramatic increase in the levels of metabotropic glutamate receptor 5, protein kinase C (PKC) gamma and phosphorylated-PKCgamma within the spinal cord dorsal horn in vgx rats, which suggests that vgx may evoke sensory nerve plasticity. Morphine produced a dose-dependent increase in the withdrawal threshold in both vgx and sham-operated rats, but the effect of a lower dose in vgx rats was weaker than that in sham-operated rats. Muscle hyperalgesia in vgx rats was also attenuated by gabapentin and amitriptyline, but was not affected by diclofenac, dexamethasone or diazepam. These findings indicate that subdiaphragmatic vagal dysfunction caused chronic muscle hyperalgesia accompanied by visceral pain and both gabapentin and amitriptyline were effective for subdiaphragmatic vagotomy-induced pain, which are partially similar to fibromyalgia syndrome. Furthermore, this chronic muscle pain may result from nociceptive neuroplasticity of the spinal cord dorsal horn.
Furuta
S
S
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
Shimizu
T
T
Narita
M
M
Matsumoto
K
K
Kuzumaki
N
N
Horie
S
S
Suzuki
T
T
Narita
M
M
D000588:Amines / Q000494:pharmacology; D000639:Amitriptyline / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D003964:Diaphragm / Q000601:surgery; D004195:Disease Models, Animal; D005356:Fibromyalgia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D000077206:Gabapentin; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000166:cytology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D014628:Vagotomy / Q000009:adverse effects*; D014630:Vagus Nerve / Q000503:physiopathology*; D020421:Vagus Nerve Diseases / Q000150:complications / Q000503:physiopathology*; D017833:Visceral Afferents / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D000701:Analgesics, Opioid; D003509:Cyclohexanecarboxylic Acids; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D000639:Amitriptyline; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; C087857:protein kinase C gamma; D011493:Protein Kinase C