Locus coeruleus modulation of dorsal horn unit responses to cutaneous stimulation

Abstract

locus coeruleus -- dorsal horn cells -- noradrenaline Neurons of the locus coeruleus (LC) and subcoeruleus area have axons which terminate in the spinal cord 1°,19'A5,2°,26. Terminals of at least some of these neurons contain noradrenalinel,11, is. The presence of dense CA terminal concentrations in the apex of the dorsal hornlZ, 19, alterations in dorsal horn interneuron responses to cutaneous stimulation following intravenous L-DOPA injection4,16 or iontophoretic application of noradrenaline (NA)la, 25, changes in pain response thresholds after des- tructive lesions of LC 7, and the apparent interaction of stimulation-produced and nar- cotic analgesic activity with functioning catecholaminergic systems 2,8° all suggest that noradrenergic brain stem nuclei are able to alter sensory transmission at the dorsal horn level. In the experiments briefly described here, the functional effects of the LC projec- tion to the lumbar spinal dorsal horn were directly evaluated by determining the chan- ges in dorsal horn cell responses, to noxious and innocuous cutaneous stimulation, caused by electrical stimulation in the region of LC. Eleven cats anesthetized with alpha-chloralose (75 mg/kg) and paralyzed with gallamine triethiodide were used. Blood pressure, end-expiratory CO2 and core temperature were continuously monito- red and maintained within accepted limits 16. The lumbar enlargement of the spinal cord was surgically exposed and covered with warm saline. A suboccipital craniectomy was done and bipolar stimulation electrodes were placed in the area of caudal LC bila- terally. Target point coordinates used were: posterior 4.0, lateral 2.8, depth-2.86,22 . Extracellular recordings from 70 dorsal horn units were done with parylene-coated microelectrodes. Once isolated, the units' receptive fields and adequate stimuli were determined. Unit responses either to innocuous hair or skin displacement with a me- chanical stimulator or to heating the skin to noxious temperature levels 8 with a Peltier contact thermode were collected. A PDP-11/34 computer was used for data collection and analysis. The effect of stimulating the ipsilateral or contralateral LC was then de- termined. Stimulus trains were 250 msec to 10 sec in length. The stimuli were biphasic pulses lasting 200 Fsec with a frequency of 100-200 Hz and amplitude varying from 20 to 400/~A. The locations of 20 of the dorsal horn recording sites were marked with