Brain Research, 321 (1984) 135-141 135 Elsevier BRE 10476 Tail-Flick Related Activity in Medullospinal Neurons HORACIO VANEGAS*, NICHOLAS M. BARBARO and HOWARD L. FIELDS Departments of Physiology, Neurology and Neurological Surgery, University of California, San Francisco, CA 94143 (U.S.A.) (Accepted April 24th, 1984) Key words: nucleus raphe magnus - - collision test - - spinal cord - - rat - - analgesia Using the classification system of Fields et al. 16 131 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 find- ings support the hypothesis16 that off- and on-cells in the RVM play a significant role in pain modulation at the spinal cord level. INTRODUCTION Neurons in the nucleus raphe magnus and adjacent structures of the rostral ventromedial medulla (RVM) modulate neuronal responses and reflexes elicited by noxious peripheral stimulationT, 15. This modulatory action is exerted by means of RVM pro- jections to the trigeminal nuclei and, via the dorsolat- eral funiculus (DLF), to the spinal dorsal hornS,6,28, 29. Thus, electrical stimulation or opioid microinjection in RVM causes inhibition of reflex and behavioral re- sponses to noxious stimulil,3,11,12,20,24,25,31, 32, as well as inhibition of nociceptive neurons located in the tri- geminal nucleit3,20,24,25 and the spinal dorsal horn14,18,30. These observations indicate that RVM neurons which project to the spinal cord play an important role in modulating nociceptive transmission. In order to understand the role of RVM neurons in pain-mod- ulation it is necessary to determine their activity un- der circumstances when nociceptive transmission is inhibited. It is well documented that RVM neurons respond to nociceptive inputs2,19,21, 22, but only recently has it been demonstrated that the activity of some RVM neurons has a definite relationship to the motor com- ponent of a nocifensive reflex, the tail-flick t6. Thus, when a rat flicks its tail in response to noxious heat, RVM neurons of one class (off-cells) abruptly halt their activity prior to the flick while neurons of anoth- er class (on-cells) suddenly increase their firing rate just before the flick. Fields et al.16 have proposed that the off-cells con- stitute the efferent limb of a pain-modulating circuit and that their turning off is necessary for the occur- rence of nocifensive reflexes such as the tail-flick. This hypothesis is supported by the findings that sys- temic morphine 17 or electrical stimulation of the mid- brain 27 concomitantly prevents the off-cells' pause and the tail-flick. Although the role of the on-cells re- quires further investigation, the close relationship between the on-cell burst and the tail-flick suggests a pain-modulatory role for this cell class as well. We have now studied whether these physiologically defined classes of neuron contribute to the descend- ing pain-modulating output of the RVM. We show * On leave from the Instituto Venezolano de Investigaciones Cientificas (IVIC), Caracas. .Correspondence and reprint requests: H. L. Fields, Department of Neurology M-794, University of California, San Francisco, CA 94143, U.S.A. 0006-8993/84/$03.00 (~) 1984 Elsevier Science Publishers B.V.