The Distribution Of 5-HT_1A Receptor In The Rat Spinal Cord And Its Role In The Nociceptive Information Transmission

The primary afferents transmitting nociceptive information from periphery to the central nervous system terminate principally in the spinal dorsal horn, which is also one of the target regions modulating nociception by the descending inhibitory system. Thus, the spinal dorsal horn plays important roles in the transmission and modulation of nociceptive information from periphery. 5-Hydroxytryptamine (5-HT) is an important neurotransmitter which undertakes many key functions via activation of different receptor subtypes. It is generally accepted that the 5-HT receptor can be divided into 7 groups including 14 subtypes. They are localized within the nervous system in different patterns, which are closely related to their functions. Up to now, there are only few autoradiographic and in situ hybridization histochemical studies concerned with the distribution of 5-HT receptor subtypes within the nervous system. Among these subtypes, 5-HTIA receptor is first cloned and studied. Phannacological and physiologic evidence on the function of this receptor has shown that it has close relationship with sensation, locomotion and parasympathetic functions. Although 5-HTIA receptor is found to distribute abundantly in the brain, detailed information is still unavailable concerning about its distribution and function in the spinal cord. Previous study using autoradiograph demonstrated that 5-HTIA receptor was majorly located within the dorsal horn. However, other studies showed that 5-HTIA receptor was chiefly located in the spinal ventral horn. Also little is known about the functions of the 5-HTIA receptor in the spinal cord. The present study was focused on the distribution of 5-HT1A receptor in the spinal dorsal horn as well as its roles in the nociceptive information transmission by using in situ hybridization histochemistry, antisense oligodeoxynucleotide (AS 0) method and behavior test. 1. Distribution of 5-HT1A receptor mRNA positive neurons within the rat spinal cord Oligonucleotide probe complementary to a part of 5-HTIA receptor mRNA was synthesized, radio-labeled according to 3?tail labeling method using [ct-35S]dATP. The results of in situ hybridization histochemistry were visualized by means of autoradiography. 5-HTIA receptor mRNA positive neurons were found throughout the spinal gray matter, but predominantly located within the superficial lamina (laminae I and II) of the dorsal horn. 2. Intrathecal ASO for 5-HT1A receptor mRNA reducing the expression of 5-HT1A receptor in the spinal cord and spontaneous pain behavior induced by subcutaneous injection of bee venom into the rat hindpaw Antisense oligodeoxynucleotide for 5-HTIA receptor mRNA was intrathecally administered once a day for 4 days. The expression of the receptor was determined in spinal cord by Western blot using antisera selective for 5-HTIA receptor at the different time points after ASO administration. Behavioral test was employed to observe the effect of intrathecal ASO on the pain behaviors induced by subcutaneous bee venom injection into the rat hindpaw. Intrathecal ASO reduced the expression of 5-~HTlA receptor within the spinal cord, the expression reached the lowest amount after 4-day-injection. While intrathecal SO had no detectable effect on it. It was observed that intrathecal ASO (once a day, 4 days) significantly decreased the spontaneous flinches induced by subcutaneous injection of bee veno...