Horacio Vanegas

Tail-flick related activity in medullospinal neurons.

Using the classification system of Fields et al. 131 neurons in the rostral ventromedial medulla (RVM) of lightly anesthetized rats were divided into 3 groups according to their response during tail-flick (TF) testing: those with an abrupt increase in activity prior to TF (on-cells); those with a sudden pause in activity prior to TF (off-cells); those with no change in activity prior to TF (neutral cells). Collision testing was performed using a cervical spinal cord stimulating electrode to determine whether these neurons projected to the cord. Conduction velocities were determined for all cord-projecting neurons. All 3 cell types projected to the cord and approximately 38% of cord-projecting neurons were flick-related (off-or on-cells). All projecting neurons were within or immediately adjacent to the nucleus raphe magnus. The mean conduction velocity of on-cell axons (17.7 m/s) was significantly greater than that of off-cell axons (10.7 m/s) and neutral cell axons (12.4 m/s). Conduction velocities for all cells were within the range for myelinated axons. These findings support the hypothesis that off-and on-cells in the RVM play a significant role in pain modulation at the spinal cord level.

Inhibition of cortically-elicited movement by electrical stimulation of the hippocampus

Abstract Some reports suggest that the hippocampus might have an inhibitory effect upon movement. In the present investigation, this hypothesis is tested by comparing the magnitude of isometric forelimb flexion elicited by stimulation of the motor cortex with the magnitude of such flexion when the cortical stimulus is preceded and accompanied by a stimulus to the hippocampus. Electrical activity of hippocampus was monitored: elicitation of afterdischarges was carefully avoided, and any data associated with them were rejected. It was found that hippocampal stimulation inhibits the motors response to cortical stimulation. This effect could not be mimicked by stimulation of medial geniculate body, optic tract or parietotemporal neocortex. The magnitude of the inhibition was proportional to the intensity of the hippocampal stimulus. Hippocampal stimulation never by itself elicited any movement. Bilateral interruption of the fornix abolished the hippocampal effect.

Midbrain stimulation inhibits tail-flick only at currents sufficient to excite rostral medullary neurons

The effects of midbrain electrical stimulation on the activity of tail-flick (TF) related neurons in the rostral ventromedial medulla (RVM) were studied. Neurons whose activity either decreased (off-cells) or increased (on-cells) immediately prior to TF were examined. Of 31 off- and on-cells, 26 (84%) showed increased activity during midbrain stimulation sufficient to suppress the TF. Furthermore, in 21 of these cells, the threshold for activation was identical to the threshold for TF suppression, and in the other 5 cells the threshold difference was less than or equal to 5 microA. This study provides evidence that off-and on-cells in the RVM mediate the antinociceptive actions of midbrain stimulation.

Spinal antinociceptive effects of cyclooxygenase inhibition during inflammation: Involvement of prostaglandins and endocannabinoids

&NA; Both cyclooxygenase‐1 and ‐2 are expressed in the spinal cord, and the spinal COX product prostaglandin E2 (PGE2) contributes to the generation of central sensitization upon peripheral inflammation. Vice versa spinal COX inhibition is considered an important mechanism of antihyperalgesic pain treatment. Recently, however, COX‐2 was shown to be also involved in the metabolism of endocannabinoids. Because endocannabinoids can have analgesic actions it is conceivable that inhibition of spinal COX produces analgesia not only by inhibition of PG synthesis but also by inhibition of endocannabinoid breakdown. In the present study, we recorded from spinal cord neurons with input from the inflamed knee joint and we measured the spinal release of PGE2 and the endocannabinoid 2‐arachidonoyl glycerol (2‐AG) in vivo, using the same stimulation procedures. COX inhibitors were applied spinally. Selective COX‐1, selective COX‐2 and non‐selective COX inhibitors attenuated the generation of spinal hyperexcitability when applied before and during development of inflammation but, when inflammation and spinal hyperexcitability were established, only selective COX‐2 inhibitors reversed spinal hyperexcitability. During established inflammation all COX inhibitors reduced release of spinal PGE2 almost equally but only the COX‐2 inhibitor prevented breakdown of 2‐AG. The reversal of spinal hyperexcitability by COX‐2 inhibitors was prevented or partially reversed by AM‐251, an antagonist at the cannabinoid‐1 receptor. We conclude that inhibition of spinal COX‐2 not only reduces PG production but also endocannabinoid breakdown and provide evidence that reversal of inflammation‐evoked spinal hyperexcitability by COX‐2 inhibitors is more related to endocannabinoidergic mechanisms than to inhibition of spinal PG synthesis.

Response of the optic tectum to stimulation of the optic nerve in the teleost Eugerres plumieri.

Summary In the teleost E. plumieri , recordings from the optic tectum in response to electrical stimuli applied to the contralateral optic nerve show 3 small negative peaks (waves 1, 2 and 3) followed by a large negative deflection formed by two components (waves 4 and 5). There follows a positive deflection (wave 6). Waves 1, 2 and 3 are characterized as presynaptic since they: (a) corresponse in latency with 3 fiber groups found in the optic nerve with conduction velocities of approximately 20, 10 and 5 m/sec; (b) retain their polarity throughout the tectal thickness; and (c) coincide in time with unitary spikes which behave as presynaptic elements and are found only in tectal layers that contain nerve fibers. Waves 4, 5 and 6, on the other hand, are characterized as postsynaptic in nature since they: (a) show polarity reversal in electrode penetrations perpendicular to the tectal surface; (b) have excitability cycles typical of postsynaptic responses; and (c) coincide in time with unitary spikes which behave as postsynaptic elements and are found in all tectal layers. Waves 4 and 5 are probably due to postynaptic excitation, and wave 6 is possibly associated with postsynaptic analysis suggest propagated dendritic activity.