title: Inflammation causes a long-term hyperexcitability in the nociceptive sensory neurons of Aplysia.
abstract: Nerve injury, tissue damage, and inflammation all cause hyperalgesia. A factor contributing to this increased sensitivity is a long-term (>24 hr) hyperexcitability (LTH) in the sensory neurons that mediate the responses. Using the cluster of nociceptive sensory neurons in Aplysia californica as a model, we are examining how inflammation induces LTH. A general inflammatory response was induced by inserting a gauze pad into the animal Within 4 days, the gauze is enmeshed in an amorphous material that contains hemocytes, which comprise a cellular immune system. Concurrently, LTH appears in both ipsilateral and contralateral sensory neurons. The LTH is manifest as increased action potential discharge to a normalized stimulus. Immunocytochemistry revealed that hemocytes have antigens recognized by antibodies to TGFbeta1, IL-6, and 5HT. When a localized inflammation was elicited on a nerve, hemocytes containing the TGFbeta1 antigen were present near axons within the nerve and those containing the IL-6 were on the surface. Western blots of hemocytes, or of gauze that had induced a foreign body response, contained a 28-kD polypeptide recognized by the anti-TGFbeta1 antibody. Exposure of the nervous system to recombinant human TGFbeta1 elicited increased firing of the nociceptive neurons and a decrease in threshold. The TGFbeta1 also caused an activation of protein kinase C (PKC) in axons but did not affect a kinase that is activated in axons after injury. Our findings, in conjunction with previous results, indicate that a TGFbeta1-homolog can modulate the activity of neurons that respond to noxious stimuli. This system could also contribute to interactions between the immune and nervous systems via regulation of PKC.
authors.affiliation: Department of Anatomy and Cell Biology, Columbia University, New York, New York 10032, USA.
authors.forename: M
authors.initials: M
authors.lastname: Farr
authors.forename: J
authors.initials: J
authors.lastname: Mathews
authors.forename: D F
authors.initials: DF
authors.lastname: Zhu
authors.forename: R T
authors.initials: RT
authors.lastname: Ambron
mesh_terms: D000818:Animals; D001048:Aplysia / Q000502:physiology*; D001370:Axonal Transport; D002478:Cells, Cultured; D004594:Electrophysiology; D006434:Hemocytes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000473:pathology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D010455:Peptides; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C