title: [Molecular mechanisms of chronic pain].
abstract: Peripheral noxious stimuli or tissue injury induce the release of excitatory amino acids (EAAs) and other neurotransmitters from primary afferent terminals in the spinal dorsal horn, which may lead to the expression of immediate early genes (IEGs) in dorsal horn neurons via activation of intracellular messengers including Ca2+ and various protein kinases. Various IEGs of fos, jun, and zinc finger families are differentially expressed in dorsal horn neurons in a time dependent manner. Protein products of these genes function as transcription factors and trigger long-lasting plastic changes in CNS neurons. Simultaneously, EAAs may activate the synthesis of prostanoids and NO, which may affect the sensitivity of dorsal horn neurons. In addition, peripheral chemical mediators such as 5-HT contribute to the peripheral hyperalgesia. These events may contribute to the establishment of persistent pain and hyperalgesia in a concerted manner. It is shown that pre-treatment, but not post-treatment, with local anesthetics or analgesics reduces expression of c-fos in spinal cord neurons and pain responses in animals, suggesting that the inhibition of intracellular events by pre-treatment with anesthetics and analgesics is effective for the reduction of persistent pain following tissue injury.
authors.affiliation: Department of Anatomy and Neurobiology, Wakayama Medical College, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tokunaga
authors.forename: E
authors.initials: E
authors.lastname: Senba
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016762:Genes, fos / Q000235:genetics; D006801:Humans; D009475:Neurons, Afferent / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010146:Pain / Q000209:etiology*; D011453:Prostaglandins / Q000378:metabolism; D015290:Second Messenger Systems; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D011453:Prostaglandins; D009569:Nitric Oxide; D012701:Serotonin