Paul A. Illich

IMPACT OF SHOCK ON PAIN REACTIVITY. I: WHETHER HYPO- OR HYPERALGESIA IS OBSERVED DEPENDS ON HOW PAIN REACTIVITY IS TESTED

Prior research has shown that exposure to shock can induce a decrease in pain reactivity (hypoalgesia). The present experiments show that, at the same time points that subjects are less responsive to radiant heat applied to the tail (the tail-flick test), tailshock elicits enhanced motor reactivity and vocalization. This enhanced responsiveness, or hyperalgesia, is observed with both magnitude (Experiment 1) and threshold (Experiment 2) measures and decays within 32 min (Experiment 2). Experiment 3 shows that the hyperalgesia decays irrespective of whether or not subjects remain in the shock context, which suggests that the loss of hyperalgesia does not reflect extinction of the context-shock association. Neither removing subjects from the shock context (Experiment 4) nor the presentation of a postshock distractor (Experiment 5) affected the hyperalgesia.

Associative learning and memory for an antinociceptive response in the spinalized rat

Prior research suggests that associative and memorial processes can modulate the activation of the endogenous antinociceptive systems. It has been generally assumed that forebrain systems play an essential role in mediating the impact of these processes. The present experiments explored whether the behavioral effects indicative of associative and memorial processes can be obtained in spinalized rats. Experiment 1 demonstrated that a conditioned nonopioid antinociception can be established after rats have experienced a spinal transection at the level of the 2nd thoracic vertebrae. Experiment 2 showed that a postshock distractor can speed the decay of shock-induced antinociception in the spinalized rat. These findings suggest that the circuitry needed to obtain associative and memorylike effects is present within the spinal cord.

Response-specific inhibition during general facilitation of defensive responses in Aplysia

Siphon responses of Aplysia have been used to examine the neural basis of nociceptive behavioral inhibition. The authors tested the response specificity and functional significance of this inhibition. Video analysis showed that strong tail-nerve shock decreased the duration of siphon constriction evoked by weak siphon shock. Tail-nerve shock also caused the appearance of a novel flaring response to the test stimulus, which resembled the siphon response to tail-nerve shock. Novel flaring responses were expressed to both mechanical and electrical siphon stimuli. Tailshock facilitated another defensive response, inking, during the period of inhibited siphon constriction. Tailshock also facilitated tail contractions evoked by weak contralateral tail stimulation during this period. These results indicate that inhibition is not generalized across defensive responses and is specific to siphon responses that interfere with directed ink ejection toward an injured site.

Role of cholinergic systems in pain modulation. I, Impact of scopolamine on environmentally induced hypoalgesia and pain reactivity

Scopolamine was found to block both brief shock-induced (3 0.75-s, 1.0-mA shocks) and conditioned hypoalgesia on the tail-flick test in rats. The drug also produced a general increase in pain reactivity as measured by both the tail-flick test and shock-induced vocalization. It was shown that this hyperalgesia cannot account for the effect of the drug on brief-shock or conditioned hypoalgesia. Scopolamine did not block the nonopioid analgesia observed after long shock (3 25-s, 1.0-mA shocks). When the effect of the drug on baseline levels of pain reactivity was controlled, it potentiated long shock-induced hypoalgesia. Scopolamine also increased reactivity to tactile stimulation, which suggests the hyperalgesia reflects a general increase in arousal. None of these effects were observed with methylscopolamine, which suggests they are not peripherally mediated.

Latent inhibition, overshadowing, and blocking of a conditioned antinociceptive response in spinalized rats

Prior research has shown that a conditioned antinociceptive response can be established in spinalized rats by pairing stimulation to one hind leg (the conditioned stimulus, or CS) with tailshock (the unconditioned stimulus, or US). This suggests that spinal mechanisms can support classical conditioning. It is well known that in intact subjects, classical conditioning is undermined by preexposure to the CS (latent inhibition) or the concurrent presentation of either a more salient CS (overshadowing) or one that has already been associated with the US (blocking). In the present paper we show that these manipulations have a similar impact on the acquisition of a conditioned antinociceptive response in spinalized rats. These findings imply that similar principles may govern the acquisition of a conditioned response across different levels of the nervous system.

The impact of shock on reactivity to a tactile stimulus

Abstract We have previously shown that exposure to either three brief (0.75 s) or three long (25 s) tail shocks can induce a strong hypoalgesia in rats as measured by tail withdrawal from radiant heat, and that these two examples of hypoalgesia are mediated by different neural systems. The present experiments evaluate whether exposure to either brief or long shock disrupts reactivity to a tactile stimulus applied to the tail. We found that subjects exposed to brief shock are hyperreactive to the tactile stimulus. This effect was observed on all of our response measures: latency to exhibit a tail movement, magnitude of tail movements, latency to vocalize, and vocalization magnitude. Similarly, exposure to long shock increased reactivity to tactile stimulation. However, this effect was only evident on three of the four measures: latency to vocalize, vocalization magnitude, and magnitude of tail movements. Implications of the results are discussed.

Conditioned changes in pain reactivity I: A discrete CS elicits hypoalgesia, not hyperalgesia, on the tail-flick test

Abstract Prior work suggests that a stimulus which has been paired with an aversive event may elicit either an increase or decrease in pain reactivity. In four experiments we attempted to isolate the variables which determine the direction of the conditioned response. In all experiments, one stimulus was paired with shock (the CS+) while another was nonreinforced (the CS−). Pain reactivity was assessed by measuring tail withdrawal from radiant heat (the tail-flick test). Experiment 1 tested whether the amount of training plays a critical role. We found that the CS+ elicits longer tail-flick latencies irrespective of whether subjects received 6 or 24 CS-US pairings. Although there was some evidence that subjects may exhibit a general hyperalgesia at 2 min after the presentation of the conditioned stimulus, the results of Experiment 2 revealed that this effect was an artifact caused by differences in the amount of time between test trials. The results of Experiment 2 also showed that the difference observed between the CS+ and CS− was not due to a CS− induced hyperalgesia. Rather, it reflects a CS+ induced hypoalgesia. Experiment 3 evaluated whether the time of day at which testing occurs is important. We found that subjects exhibit conditioned hypoalgesia when tested in either the light or dark portion of the light-dark cycle. In Experiment 4 we examined whether it matters if subjects are tested in the training context or a neutral context. We found that subjects exhibit conditioned hypoalgesia during the CS+ irrespective of where they are tested. The results suggest that a CS+ elicits hypoalgesia, not hyperalgesia, on the tail-flick test over a wide range of conditions.

Conditioned changes in pain reactivity: II. In search of the elusive phenomenon of conditioned hyperalgesia.

Previous research suggests that a stimulus that has been paired with an aversive event can elicit either an increase (hyperalgesia) or decrease (hypoalgesia) in pain reactivity in rats. Attempts have recently been made to isolate the variables that determine the direction of the conditioned response. Very little evidence has been found for conditioned hyperalgesia when a spinally mediated measure of pain reactivity (the tail-flick test) was used. In the present study, the impact of a conditioned stimulus was assessed using a procedure modeled after one in which conditioned hyperalgesia was obtained with the tail-flick test (Davis & Hendersen, 1985, Experiment 4). With this training paradigm, a discrete conditioned stimulus was found to elicit hypoalgesia but not hyperalgesia.

The impact of naltrexone and morphine tolerance on mild shock-induced hypoalgesia

We have previously shown that exposure to mild shock elicits a strong hypoalgesia on the tailflick test in rats. The present studies explored the role of endogenous opioids in producing this hypoalgesia. Experiment 1 evaluated the impact offive doses ofnaltrexone (0,0.44,1.75,7, and 28 mg/kg); Experiment 2100ked at the impact ofmorphine tolerance. Both a low dose ofnaltrexone (1.75 mg/kg) and morphine tolerance attenuated the hypoalgesia observed 6–10 min after mild shock. By contrast, neither morphine tolerance nor a high dose of naltrexone (28 mg/kg) had a significant impact on the hypoalgesia observed 2 min after shock. These findings suggest that mild shock elicits both a transient nonopioid and a long-Iasting opioid hypoalgesia.

Long-term effects of food deprivation. II: Impact on morphine reactivity

Exposure to a series of inescapable shocks elicits a hormonally mediated opioid hypoalgesia in rats. In addition, it has a long-term effect on the opioid system: it increases reactivity to a low dose of morphine. Here we looked at whether another manipulation that elicits a hormonally mediated opioid hypoalgesia—food deprivation—has a similar sensitizing effect. Subjects were placed on a restricted diet for 48 h. Opiate reactivity was then assessed 24 h after food was returned. In Experiment 1, previously food-deprived subjects exhibited a stronger hypoalgesia on the tailflick test 30 min after an injection of morphine. In Experiment 2, a history of food deprivation increased the duration of morphine hypoalgesia as well as its onset. In Experiment 3, food deprivation per se induced hypoalgesia, but only during the early part of the dark cycle.