PEPTIDE PLASTICITY IN PRIMARY SENSORY NEURONS AND SPINAL-CORD DURING ADJUVANT-INDUCED ARTHRITIS IN THE RAT - AN IMMUNOCYTOCHEMICAL AND IN-SITU HYBRIDIZATION STUDY

Chronic polyarthritis due to complete Freund's adjuvant injection is c haracterized by severe inflammation and pain. In the present immunocyt ochemical and in situ hybridization study on the rat, we quantitativel y investigated peptide and peptide messenger RNA expression in the sen sory circuit at the spinal level, i.e. sensory neurons in the dorsal r oot ganglia and in nerve endings and local neurons in the dorsal horn of the spinal cord. The immunocytochemical experiments were carried ou t five, 13 and 21 days after complete Freund's adjuvant injection, whe reas in situ hybridization study was performed after 21 days from comp lete Freund's adjuvant injection. The main results in the present stud y are the following: (i) a decrease in substance P-, calcitonin gene-r elated peptide-and galanin-like immunoreactivities in dorsal root gang lia is observed five days after complete Freund's adjuvant injection, with recovery (calcitonin gene-related peptide and galanin) or even an increase (substance P) after 21 days; (ii) calcitonin gene-related pe ptide, substance P and galanin peptide levels are increased in dorsal root ganglia after 21 days; (iii) opioid peptide (enkephalin and dynor phin), substance P and galanin messenger RNAs are strongly up-regulate d in dorsal horn neurons after 21 days; (iv) neuropeptide Y content in creases in dorsal root fibres and neuropeptide Y messenger RNA levels decrease in spinal neurons after 21 days; and (v) a dramatic decrease in calcitonin gene-related peptide and cholecystokinin messenger RNA l evels is found in motoneurons in the ventral horn after 21 days. These data indicate that peptide expression in dorsal root ganglia and the spinal cord is markedly influenced by severe inflammation with distinc t and individual temporal patterns, which are also related to the seve re rearrangement of joint structure during polyarthritis. The increase in galanin levels in dorsal root ganglia 21 days after complete Freun d's adjuvant injection can be related to the structural damage of nerv e fibres. Thus, there may be a transition from inflammatory to neuropa thic pain, which could have consequences for treatment of patients wit h rheumatoid arthritis. (C) 1997 IBRO. Published by Elsevier Science L td.