Inflammation causes a long-term hyperexcitability in the nociceptive sensory neurons of Aplysia

Nerve injury, tissue damage, and inflammation all cause hyperalgesia. A fac tor contributing to this increased sensitivity is a long-term (>24 hr) hype rexcitability (LTH) in the sensory neurons that mediate the responses. Usin g the cluster of nociceptive sensory neurons in Aplysia californica as a mo del, we are examining how inflammation induces LTH. A general inflammatory response was induced by inserting a gauze pad into the animal. Within 4 day s, 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 incre ased. action potential discharge to a normalized stimulus. Immunocytochemis try revealed that hemocytes have antigens recognized by antibodies to TGF b eta 1, IL-6, and 5HT. When a localized inflammation was elicited on a nerve , hemocytes containing the TGF beta 1 antigen were present near axons withi n the nerve and those containing the IL-6 were on the surface. Western blot s of hemocytes, or of gauze that had induced a foreign body response, conta ined a 28-kD polypeptide recognized by the anti-TGF beta 1 antibody. Exposu re of the nervous system to recombinant human TGF beta 1 elicited increased firing of the nociceptive neurons and a decrease in threshold. The TGF bet a 1 also caused an activation of protein kinase C (PKC) in axons but did no t affect a kinase that is activated in axons after injury. Our findings, in conjunction with previous results, indicate that a TGF beta 1-homolog can modulate the activity of neurons that respond to noxious stimuli. This syst em could also contribute to interactions between the immune and nervous sys tems via regulation of PKC.