Co-localization of substance P and dopamine beta-hydroxylase with growth-associated protein-43 is lost caudal to a spinal cord transection

After spinal cord injury, abnormal responses of spinal cord neurons to sens ory input lead to conditions such as autonomic dysreflexia, urinary bladder dyssynergia, muscle spasticity and chronic pain syndromes. These responses suggest that the spinal cord undergoes marked reorganization after an inju ry. In previous studies, we demonstrated changes in individual patterns of immunoreactivity for growth-associated protein-43, dopamine beta-hydroxylas e and substance P that suggest growth and/or changes in expression of neuro transmitter enzymes and peptides in the cord caudal to a transection injury . In the present study we determined whether (i) growth-associated protein- 43 and dopamine beta-hydroxylase or substance P were co-expressed in the sa me neurons prior to cord injury, and (ii) these patterns of expression chan ged after injury. A change in co-localization patterns caudal to an injury would suggest diversity in responses of different populations of spinal neu rons. We used double-labelling immunocyto- chemistry to determine whether e ither dopamine beta-hydroxylase or substance P was co-localized with growth -associated protein-43 in control rats and in rats one, two or six weeks af ter spinal cord transection. We focused on the intermediate gray matter, es pecially the sympathetic intermediolateral cell column. In control rats, fi bres travelling in a stereotyped ladder-like pattern in the thoracic gray m atter contained growth-associated protein-43 co-localized with dopamine bet a-hydroxylase or substance P. In spinal rats, such co-localization was also observed in spinal cord segments rostral to the cord transection. In contr ast, caudal to the transection, substance P and growth-associated protein-4 3 were found in separate reticular networks. Immunoreactivity for dopamine beta-hydroxylase disappeared in fibres during this time, but was clearly pr esent in somata. Immunoreactivity for growth-associated protein-43 was also found in somata, but never co-localized with that for dopamine beta-hydrox ylase. These observations demonstrated co-localization of growth-associated protei n-43 with dopamine beta-hydroxylase and substance P in descending spinal co rd pathways. Caudal to a cord transection, this co-localization was no long er found, although each substance was present either in an abundant neural network or in somata. One population of spinal neurons responded to cord in jury by expressing the growth-associated protein, whereas two others change d in the intensity of their expression of neurotransmitter peptides or enzy mes or in the abundance of fibres expressing them. Thus, three populations of spinal neurons had distinct responses to cord injury, two of them increa sing their potential input to spinal sensory, sympathetic or motor neurons. Such responses would enhance transmission through spinal pathways after co rd injury. (C) 1998 IBRO. Published by Elsevier Science Ltd.