Up-regulation of fatty acid metabolizing-enzymes mRNA in rat spinal cord during persistent peripheral local inflammation.
Persistent peripheral inflammation is associated with repetitive painful inputs into the spinal cord, leading to a chronic pain state. Related dramatic changes occur in the central nervous system (CNS) including central sensitization, which results in hyperalgesia. This neural plasticity involves in part fatty acids as functional and structural compounds. We hypothesized that central modification of fatty acids metabolism might occur after prolonged peripheral noxious stimulation. In the present study, the regulation of genes involved in fatty acids metabolism in the rat CNS was investigated during a chronic pain state. Using semiquantitative RT-PCR, we explored in the neuraxis the mRNA expression of brain acyl-CoA synthetases (ACS) and acyl-CoA oxidase (ACO), which are major fatty acid-metabolizing enzymes, following complete Freund's adjuvant (CFA) injection into a hind paw. Similar spinal up-regulation of the isoforms ACS2, ACS3, ACS4, and of ACO was detected early after 30 min, reaching a maximal after 6 h post-injection. Other peaks were also observed after 4 and 21 days post-inoculation, corresponding to the acute and chronic inflammation, respectively. Induction occurred only in the lumbar spinal cord ipsilaterally to the inflamed paw and was completely inhibited by a local anaesthesia of the sciatic nerve, suggesting a neural transmission of the inducing signal. Moreover, intrathecal injection of MK801, a noncompetitive NMDA antagonist, partially prevented these inductions, highlighting the involvement of the neurotransmitter glutamate in the central ACS and ACO up-regulation. These findings suggest that the fatty metabolism is stimulated in the CNS during a chronic pain state.
Benani
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A
Laboratoire de Pharmacologie, Unité Mixte de Recherche 7561 CNRS-Université Henri Poincaré Nancy I, Faculté de Médecine, 54505 Vandoeuvre-les-Nancy, France.
Vol
C
C
Heurtaux
T
T
Asensio
C
C
Dauça
M
M
Lapicque
F
F
Netter
P
P
Minn
A
A
D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D015256:Coenzyme A-Transferases / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007839:Functional Laterality; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D010991:Plethysmography / Q000379:methods; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000201:enzymology* / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D018691:Excitatory Amino Acid Antagonists; D005227:Fatty Acids; D007527:Isoenzymes; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C034661:ribosomal proteins L27; D016291:Dizocilpine Maleate; D005620:Freund's Adjuvant; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D042962:Acyl-CoA Oxidase; D015256:Coenzyme A-Transferases; C031212:acyl-CoA transferase