Supraspinal actions of pentobarbital on transmission through the spinothalamic tract

Despite the advances made in our understanding of the molecular mechanistic actions of general anesthetics very little is known about the in vivo neural circuits involved in creating the state of general anesthesia. To date the common consensus is that general anesthetics act ubiquitously within the CNS. Recently, (Devor and Zalkind, 2001) have reported that microinjections of pentobarbital (PB) into a discrete brainstem focal area of conscious rats induced a classical, reversible general anesthesia-like behavioral state. The authors concluded that this area, termed the mesopontine tegmental anesthesia area (MPTA), may be important for the induction of general anesthesia. The purpose of the present project was to study the neurophysiological basis of the analgesia, which accompanied the state of general anesthesia induced by PB microinjections into the MPTA that was reported by (Devor and Zalkind, 2001). Here, sensory inflow via the spinothalamic tract (STT), a classical spinal nociceptive pathway in the rat, was assessed using single neuron extracellular recording techniques before, during and after microinjections of PB into the MPTA. Spontaneous firing rate (SFR), antidromic firing index (FI) and sciatic as well as sural nerve-evoked responses (Sc-, Su-ER) of STT neurons in isoflurane-anesthetized rats were quantified before as well as 2, 15, 30 and 60 min following bilateral microinjections of either PB (200 micrograms/side) or vehicle control solution (Vh, 1 microliter/side) into the MPTA. The group mean SFR, FI as well as magnitudes of Sc-, Su-ER of STT neurons were significantly and reversibly reduced following PB microinjections compared to corresponding baseline measurements. There were no significant changes in any of the three parameters following microinjections of Vh compared to the pre-microinjection baseline responses. The results from this study indicate that analgesia, which occurs during the anesthesia-like state following microinjections of PB into the MPTA, may be due to attenuation of sensory inflow through the STT. The suppression of STT neurons likely occurs via direct and/or indirect descending pathways from the MPTA to the spinal cord. This study provides the first direct electrophysiological evidence for the analgesia caused by PB microinjections into the rat MPTA.Pharmaceutical Sciences, Faculty ofGraduat