TIME-DEPENDENT CHANGES IN BOLTON-HUNTER-LABELED I-125 SUBSTANCE-P BINDING IN RAT SPINAL-CORD FOLLOWING UNILATERAL ADJUVANT-INDUCED PERIPHERAL INFLAMMATION

Time-dependent changes in Bolton-Hunter-labeled I-125-substance P binding occurred in the dorsal horn of the spinal cord following unilateral adjuvant-induced inflammation in the hindpaw of the rat. Inflammation was characterized by measures of edema and hyperalgesia. Edema and hyperalgesia were both present 6h after induction of inflammation. However, by eight days, hyperalgesia had dissipated while edema persisted. Six hours after the induction of inflammation, widespread decreases in Bolton-Hunter-labeled I-125-substance P binding occurred on both sides of the dorsal horn of spinal level L4 in comparison to the control group. However, by two days, widespread increases in Bolton-Hunter-labeled I-125-substance P binding occurred on both sides of the spinal cord at level L4 compared to the control group. The increase in radioligand binding was primarily due to a 10-fold increase in affinity of neurokinin-1 receptors for substance P. At later time-points of four and eight days, Bolton-Hunter-labeled I-125-substance P binding remained increased only in laminae I/II on the side of the spinal cord ipsilateral to inflammation. The changes in Bolton-Hunter-labeled I-125-substance P binding suggest that alterations in substance P synaptic transmission in the spinal cord may contribute to the increased excitability of spinal neurons that accompanies adjuvant-induced peripheral inflammation.