No abstract

Animals eat rather than react to moderate pain. Here, we examined the behavioral, hedonic, and neural requirements for ingestion analgesia in ad libitum fed rats. Noxious heat-evoked withdrawals were similarly suppressed during self-initiated chocolate eating and ingestion of intraorally infused water, sucrose, or saccharin, demonstrating that ingestion analgesia does not require feeding motivation, self-initiated food procurement, sucrose, or calories. Rather, food hedonics is important because neither salt ingestion nor quinine rejection elicited analgesia. During quinine-induced nausea and lipopolysaccharide (LPS)-induced illness, conditions when chocolate eating was presumably less pleasurable, analgesia accompanying chocolate consumption was attenuated, yet analgesia during water ingestion was preserved in LPS-injected rats who showed enhanced palatability for water within this context. The dependence of ingestion analgesia on the positive hedonics of an ingestate was confirmed in rats with a conditioned taste aversion to sucrose: after paired exposure to sucrose and LPS, rats no longer showed analgesia during sucrose ingestion but continued to show analgesia during chocolate consumption. Eating pauses tended to occur less often and for shorter durations in the presence of ingestion analgesia than in its absence. Therefore, we propose that ingestion analgesia functions to defend eating from ending. Muscimol inactivation of the medullary raphe magnus blocked the analgesia normally observed during water ingestion, showing the involvement of brainstem endogenous pain inhibitory mechanisms in ingestion analgesia. Brainstem-mediated defense of the consumption of palatable foods may explain, at least in part, why overeating tasty foods is so irresistible even in the face of opposing cognitive and motivational forces.

Feeding is essential for survival, whereas withdrawal and escape reactions are fundamentally protective. These critical behaviors can compete for an animal's resources when an acutely painful stimulus affects the animal during feeding. One solution to the feeding-withdrawal conflict is to optimize feeding by suppressing pain. We examined whether rats continue to feed when challenged with a painful stimulus. During feeding, motor withdrawal responses to noxious paw heat either did not occur or were greatly delayed. To investigate the neural basis of sensory suppression accompanying feeding, we recorded from brainstem pain-modulatory neurons involved in the descending control of pain transmission. During feeding, pain-facilitatory ON cells were inhibited and pain-inhibitory OFF cells were excited. When a nonpainful somatosensory stimulus preactivated ON cells and preinhibited OFF cells, rats interrupted eating to react to painful stimuli. Inactivation of the brainstem region containing ON and OFF cells also blocked pain suppression during eating, demonstrating that brainstem pain-modulatory neurons suppress motor reactions to external stimulation during homeostatic behaviors.homeostasis ͉ nociceptive modulation ͉ pain ͉ raphe magnus ͉ ON and OFF cells B ehaviors such as eating, drinking, micturition, and defecation are essential for an organism's survival and are affected by exposure to aversive stimuli. Stress-induced eating and defecation occur across species and can be triggered by exposure to a painful stimulus (1-4). Yet, very little is known about the effects of feeding (eating and drinking), micturition, and defecation on pain sensitivity. In food-deprived animals, eating takes precedence over pain-motivated behaviors. During eating, fooddeprived cats were less likely to withdraw from acute noxious cutaneous heat (5), and food-deprived chickens showed fewer pain-motivated behaviors in response to chronic pain induced by sodium urate (6). However, responses to a painful stimulus are affected by the hunger͞satiation state (7), and it remains to be determined whether these analgesic effects can be generalized to animals that have been fed freely. Consequently, the aim of Experiment 1 was to examine whether the drive to satisfy hunger still overrides the need to avoid pain in non-food-deprived animals. We found that feeding suppressed pain in rats that were fed ad libitum.The suppression of pain during feeding indicates the activation of endogenous pain modulatory pathways. The brainstem ventromedial medulla (VMM) is a critical area in the descending control of pain and is the final common pathway from the brain to the spinal cord (8-11). The VMM modulates pain bidirectionally: its activation can produce either pain facilitation or pain inhibition (10-16). The pain-facilitatory and pain-inhibitory effects are thought to be mediated by two populations of neurons with opposing responses to noxious stimulation and morphine (17)(18)(19)(20). Cells activated by noxious stimulation are inhibited by opioids. These cel...

Kava (Piper methysticum) and alcohol were administered either separately or in combination to human subjects. Self-reports of their levels of impairment and intoxication were collected, and performance skills on a number of cognitive and visuomotor tests were determined, before and three times after consumption of the experimental drink. Kava alone had no effect on reported condition. In contrast, alcohol produced marked changes in each of the five subjective measures, all of which were in the direction of lowered ability. The combination of these two substances produced even larger negative changes on these measures. In the cognitive tests, kava produced a decrement in performance on Digit Symbol Coding. Alcohol produced a significant decrease in performance on a divided attention test, which was almost entirely on the peripheral, discontinuous component of the test. The combination of kava and alcohol produced an even greater decrease in performance on this test, and in the same component. The present findings suggest that kava alone has little effect on reported condition and cognitive performance, but appears to potentiate both perceived and measured impairment when combined with alcohol.

Medullary raphe magnus (RM) ON and OFF cells are thought to modulate spinal nociception by gating withdrawals evoked by noxious stimulation. To test whether withdrawal initiation is the target of RM modulation, we examined the relationship between ON and OFF cell discharge and motor withdrawal evoked by noxious laser heat in halothane-anesthetized rats. The cellular responses of both cell types began during the 50 msec after onset of the tail flick, peaked within 200 msec, and outlasted the duration of the motor reaction. Thus, it is unlikely that the target of ON and OFF cell modulation is withdrawal initiation; instead, ON and OFF cells may modulate reactions to repeated noxious stimulation. We therefore tested whether laser heat-evoked changes in RM cell discharge were predictive of the modulatory effects of one noxious stimulus on the reaction to a subsequent noxious stimulus. Two pulses of laser heat were presented at interpulse intervals of 0.8, 2.0, or 10.0 sec. The motor withdrawal evoked by the second pulse was significantly enhanced relative to that evoked by the first pulse. The observed motor enhancement depended on supraspinal input because it was not present in spinalized rats. Comparison of the relative changes in motor and cellular activity preceding double laser heat stimulation revealed parallel changes between motor facilitation, decreases in OFF cell discharge, and increases in ON cell discharge. This finding suggests a preparatory role for RM ON and OFF cells in enhancing reactions to a noxious stimulus that closely follows another noxious stimulus.