Suppression of shock elicited target biting by analgesic midbrain stimulation

Rats with chronic electrodes in or near the central gray (PVG) of the midbrain were tested with a tail pinch to determine analgesic brain stimulation parameters. Then blocks of tail shock, adjusted to a level that produced consistent biting on an inanimate target, were alternated with blocks of tail shock preceded by PVG stimulation. Biting following the tail shock was reduced or eliminated when the brain stimulation preceded the shock. It was concluded that stimulation in the PVG region reduces target biting produced by nociceptive stimulation, probably via an analgesic effect. Also, no biting was associated with brain stimulation, indicating that the bite suppression function is separate from the attack producing function of other central gray areas.     

Acceleration of tail pinch-induced feeding in rats by analgesic effect of neurotropin.

Mechanisms of tail pinch-induced feeding and effects of neurotropin (NSP), an extract from the inflamed skin of rabbit inoculated with vaccinia virus, on behavioral responses were investigated in rats. Treatment of a 5-min tail pinch (tail pinch I) induced feeding response. An intensified 15-min tail pinch (tail pinch II) provoked emotional reactions besides feeding behavior. The rate of food intake (food intake/tail pinch duration) during tail pinch II was less than that at tail pinch I. Intraperitoneal administration of NSP (100 mg/kg/day) by itself produced no remarkable change in feeding or emotional behavior. However, NSP-treated rats increased eating size and prolonged eating duration during tail pinch I. Pretreatment of NSP increased feeding behavior more potently at tail pinch II than at tail pinch I and decreased the incidence of emotional reactions at tail pinch II. The results suggest that NSP, by its analgesic action, may modulate behavioral responses during tail pinch treatment through selective blockade of the nociceptive and feeding-inhibitory information, but not through the nonnociceptive and feeding-excitatory signals.     

Tail pinch behavior and analgesia in diabetic mice

Mild tail pinch induced “consummatory” behaviors in mice. The major tail pinch behavior appeared to be chewing with food ingestion occurring possibly as an epiphenomenon. All tail pinch behaviors were obliterated by the dopamine antagonist haloperidol; and the opiate antagonist, naltrexone, decreased eating without altering chewing. The combination of dopamine blockade and tail pinch induced jumping behavior in mice. Diabetic mice showed increased tail flick latencies to radiant heat and to the induction of tail pinch behaviors, displaying these behaviors less commonly than their homozygote and heterozygote littermate controls.     

Comparison of the effects of brain dopamine-depleting lesions upon oral behaviors elicited by tail pinch and electrical brain stimulation

Rats with extensive brain dopamine (DA) depletions subsequent to 6-hydroxydopamine (6-OHDA) intraventricular injections (2×200 μg) showed relatively normal food-directed responses to tail pinch and to electrical stimulation of the lateral hypothalamus. These eating and gnawing behaviors occurred even in animals that were still spontaneously aphagic after the brain lesion. In contrast, rats with similar brain DA depletions produced by a single intraventricular injection of 250 μg 6-OHDA showed a permanent abolition of electrically-elicited eating, and a chronic reduction in tail pinch behaviors. Rats treated with intranigral 6-OHDA sustained essentially complete striatal and 90% nucleus accumbens DA depletions; they showed a marked absence of both spontaneous and pinch-elicited oral behaviors. We discuss the possible parallels between tail pinch- and electrically-elicited behaviors, their relationship to naturally occurring behavior patterns, and the necessary or sufficient supportive role of nigrostriatal DA.     

Digging and biting induced by pinch stimuli and lateral hypothalamic electrical stimulation

Eight of 15 tail pinched rats displayed sand digging responses similar to those reportedly elicited during electrical stimulation of the lateral hypothalamus (ESLH); however, pinched subjects also engaged in a vigorous biting that was directed at the sand. Hypothalamically stimulated rats failed to display such a strong biting response; and while a majority of animals examined during both pinch and ESLH displayed consistent digging activity, some subjects failed to respond identically to the two treatments. The results of this investigation present some support and some interpretative complexities for the hypothesis that pinch and stimulation activate a unitary nonspecific motivational system.     

Tail pinch induced consummatory behaviors are associated with analgesia

Pinching the tail of a rat results in a set of consummatory behaviors including chewing, eating and licking. In the present study, the effect of tail pinch on pain thresholds was evaluated using the hot-plate and writhing tests. Continuous tail pinch resulted in chewing and markedly lengthened the latency to hind-paw licking and jumping (hot-plate test) when compared with control rats and totally eliminated writhing behaviors. Tail pinch (which induced chewing) for one minute prior to the analgesic testing also prolonged the latency of hot plate-induced behaviors and suppressed the number of writhing behaviors. Naloxone reversed the tail pinch induced analgesia as measured by the hot-plate test, but did not reverse tail pinch-induced analgesia as measured by the writhing test.     

Tail pinch induced eating: psychogenetic comparison of Roman high- and low-avoidance rats

Consummatory behavior elicited by mild tail pinch in the presence of solid food was studied in male Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh) rats. RLA/Verh rats, characterized as the more emotional of the two rat lines, exhibited significantly shorter latencies to bite and eat solid food during tail pinch than the RHA/Verh rats. Treatment with 6, 12 and 24 mg/kg sodium pentobarbital prior to tail pinch failed to increase the elicited eating in either rat line.     

Tail pinch-induced changes in the turnover and release of dopamine and 5-hydroxytryptamine in different brain regions of the rat.

Tail pinch was administered through a paper clip attached to the rat's tail. The ex vivo changes in the metabolite/transmitter ratio were used as a measure of changes in the turnover of dopamine and 5-hydroxytryptamine. After a 2-min tail pinch dopamine turnover was increased in the striatum but not in the frontal cortex, hypothalamus or olfactory tubercle; 5-hydroxytryptamine turnover was increased in frontal cortex and hippocampus and was unchanged in striatum, hypothalamus and olfactory tubercle. Microdialysis was used to monitor the changes in extracellular neurotransmitter and metabolite concentrations during and after tail pinch. A 5-min tail pinch caused a rapid rise of both dopamine in the striatum and 5-hydroxytryptamine in the hippocampus. There was a smaller increase in the 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid and only a non-significant increase in the dopamine metabolite 3,4-dihydroxyphenylacetic acid.     

Effects of early malnutrition on tail pinch-induced behavior of the rat

To determine if rats malnourished early in life are hyperresponsive to aversive stimulation their responses to tail pinch were measured in three experiments. Early malnutrition was induced by feeding the mothers an 8% casein diet from 5 weeks before mating until the pups were weaned at 21 days of age. Well-nourished offspring were born to mothers fed a 25% casein diet. At weaning half of the pups in each group were switched to the other diet. They were 60–100 days old when tested. Neither the latency to the first response elicited by tail pinch nor the total duration of stimulus-bound behavior indicated that the rats malnourished as preweanlings were hyperresponsive. In all three experiments, however, rats subjected to early malnutrition responded differently than well-nourished animals, irrespective of the dietary treatment at the time of testing. Malnourished rats gnawed more than they licked food and other objects; well-nourished rats did the opposite. Measurements of food weights confirmed the observation that eating was an infrequent rather than a predominant behavior.     

Tail pinch induces sexual behavior in olfactory bulbectomized male rats

Adult male Long-Evans rats were subjected to bilateral olfactory bulbectomy, sham surgery or no treatment. Of 34 bulbectomized rats, 24 failed to ejaculate on either of 2 tests with a primed ovariectomized female. All control animals exhibited normal sexual behavior, and 10 bulbectomized animals ejaculated at least once during the 2 tests. Later histological examination revealed a relationship between size of lesion and extent of behavioral deficits. After a third test, 16 nonejaculatory animals were subjected to a tail pinch (TP) procedure, immediately followed by a fourth test. The remaining 8 nonejaculatory animals were tested similarly, but without tail pinch. Ten of the 16 tail pinch animals showed complete sexual behavior on the first test, while 2 additional animals began to copulate after a second TP procedure 4 days later. Only 1 of the 8 animals not receiving TP ejaculated on these tests. Thus, TP applied shortly before sexual behavior tests can induce copulation in some males whose behavior had been disrupted by olfactory bulbectomy.     

Hypothalamic neuron involvement in integration of reward, aversion, and cue signals

The lateral hypothalamus (LHA) is involved in integrative functions related to emotion, reward, aversion, and learning. It is, however, unclear whether the medial forebrain bundle (MFB) forms a substrate common to the anterior and posterior hypothalamic areas or whether information regarding rewarding and aversive stimuli converges on and is integrated by the same hypothalamic neuron. In the present study, unit activity in the LHA and lateral preoptic-anterior hypothalamic area (lPOA-AHA) of the rat was recorded during discrimination learning of cue tone stimuli (CTS) that predicted glucose or intracranial self-stimulation (ICSS) as rewarding stimuli, or electric shock or tail pinch as aversive stimuli, using identical behavior, licking. We examined functional differences between the LHA and lPOA-AHA. In positive reinforcement experiments a rat was rewarded by glucose or ICSS only when it licked a spout presented in front of its mouth. The threshold current for ICSS was used. In negative reinforcement experiments an aversive stimulus, either electric shock or tail pinch was applied if the rat did not lick the spout. The strengths of electric shock and tail pinch were selected to produce an avoidance ratio less than 20-30%, averaged in all trials. The activity of 507 LHA and 249 lPOA-AHA neurons was analyzed during both glucose and ICSS trials. The effects of both glucose and ICSS on the same LHA or lPOA-AHA neuron were usually in the same direction, i.e., either both excitatory or both inhibitory. Of 143 LHA and 44 lPOA-AHA neurons that responded to both rewards, the responses of 117 (81.8%) LHA and 35 (79.5%) lPOA-AHA neurons to both stimuli were similar. The activity of 131 LHA and 153 lPOA-AHA neurons was analyzed in both electric shock and tail pinch trials. The effects of both electric shock and tail pinch on the same LHA or lPOA-AHA neuron were usually in the same direction. Of 29 LHA and 27 lPOA-AHA neurons that responded to both aversive stimuli, the responses of 28 (96.6%) LHA and 25 (92.6%) lPOA-AHA neurons to both were similar. The activity of 170 LHA and 195 lPOA-AHA neurons in response to both rewarding glucose and/or ICSS stimulation and aversive electric shock and/or tail pinch was analyzed. About one-third of the neurons in each area were reward specific (57/170 in LHA; 63/195 in lPOA-AHA), whereas relatively few were aversion specific in each area (21/170 in LHA; 15/195 in lPOA-AHA).(ABSTRACT TRUNCATED AT 400 WORDS)     

Corticotropin-releasing factor as well as opioid and dopamine are involved in tail-pinch-induced food intake of rats

Several kinds of stress such as psychological stress, restraint, and foot shock inhibit feeding behavior through corticotropin-releasing factor (CRF). In contrast, a mild tail pinch increases food intake in rats. Although dopamine and opioid are thought to be involved in tail-pinch-induced food intake, it is unknown whether CRF participates in this phenomenon. Therefore, we attempted to clarify this issue using rats. A 30-s tail pinch increased food intake in 30 min after the tail pinch, and this increase was blocked by intraperitoneal injection of CRF receptor type 1 selective antagonist. CRF increased food intake in 30 min after intracerebroventricular injection at a dose of 2 or 10 ng, and this increase was also blocked by CRF receptor type 1 antagonist. Tail-pinch- or CRF-induced food intake was blocked by naloxone, pimozide, and spiperone. These results suggest that CRF, through CRF receptor type 1 as well as opioid and dopaminergic systems, are involved in the mechanism of tail-pinch-induced food intake. The results also suggest that brain CRF has dual effects on food intake, hyperphagia and anorexia, in a stress-dependent manner.     

Clip-induced analgesia: noxious neck pinch suppresses spinal and mesencephalic neural responses to noxious peripheral stimulation

Pinch of the nape of the neck, of mice, with a serrated clip, produces immobility and lack of responsiveness to noxious stimulation. In this study we attempted to determine whether clip application produces true blockade of nociception, independent of its immobilizing effect, and examined the level of the neuroaxis at which such an effect takes place. To this end nociception was measured using indices not requiring a motor response. Neck pinch eliminated the elevation of heart rate induced by noxious pinch of the tail without affecting heart rate by itself providing evidence for its analgesic effect. Direct evidence that neck pinch suppresses the transmission of noxious information is also provided. Neck pinch inhibits neural activity evoked by noxious peripheral stimulation while exerting minimal effects on the effects of nonnoxious stimuli. Thus, sensory evoked activity in the periaqueductal gray area, elicited by noxious electrical stimulation, but not innocuous stimuli, is inhibited by neck pinch. Similarly, neck pinch inhibits the response of spinal cord neurons to noxious but not nonnoxious stimulation. It, therefore, appears that neck pinch produces true analgesia by activating supraspinal systems which in turn acts to inhibit the transmission of nociception both at spinal and supraspinal levels.     

Are 'neutral cells' in the rostral ventro-medial medulla subtypes of on- and off-cells?

The classification of cells in the rostral ventromedial medulla (RVM) is based on the response pattern to noxious tail heat: on-cell activity increased, off-cell activity decreased, and activity of neutral cells is unaffected by noxious heat tail stimulation. It is generally assumed that on-, off- and neutral cells respond equally to noxious stimulation applied anywhere on the body surface, but so far this assumption has not been systematically examined. In the present study the effects of thermal and mechanical stimuli applied to the tail, the extremities and the orofacial region on the extracellularly recorded activity of 14 neutral cells were investigated in lightly anesthetized rats. Although the neutral cells did not respond to noxious tail heat, all of them responded to most of the other stimuli in an on- or off-manner. Especially cell responses to pinch stimuli applied to the skin of the ear, the forehead and the nose differed from the neutral behavior. The fact that the neutral cells in the present study responded in an off- or on-manner by applying noxious stimuli different from noxious tail heat suggests that these cells are possibly subtypes of on- and off-cells in the RVM.     

Tail pinch-induced eating does generalize to a nonpreferred but familiar food.

Mild tail pinch has been reported to induce many of the same behaviors as electrical stimulation of the brain. In this study a 4 min tail pinch induced significant eating of either canned dog food or rat chow. In contrast to eating produced by brain stimulation, which does not generalize along the appropriate stimulus dimension of food objects, removal of the tail pinch-induced eaters' preferred food resulted in their eating another nonpreferred, but familiar food. With only the nonpreferred food available, intake of animals who preferred rat chow increased and intake of animals who preferred dog food decreased compared to their respective controls, although no initial differences existed. When both foods were again available, $\text{13}\text{18}$ animals retained their initial preference while $\text{5}\text{18}$ showed no preference. No animals reversed their preference. Tail pinch-induced eating may be more similar to normal eating than that produced by electrical brain stimulation.     

A simple device for eliciting tail pinch induced behavior in the rat

The device described is an inexpensive reliable means for eliciting tail pinch behaviors. As an improvement over previous methods it allows a wide range of stimulus parameters with minimal restriction of movement or distraction of the animal.     

Central sites involved in lateral hypothalamus conditioned neural responses to acoustic cues in the rat

1. Unit activity in the lateral hypothalamus (LHA) of the rat was recorded during discrimination learning of cue-tone stimuli (CTS) predicting glucose (CTS1+) or intracranial self-stimulation (ICSS) (CTS2+) as positive reinforcement or electric shock (CTS1-) or tail pinch (CTS2-) as negative reinforcement. The same action, licking, was used as the behavioral response to all stimuli. Procaine hydrochloride, a local anesthetic, was microinjected into the ventral tegmental area (VTA) and the amygdala (AM). LHA neuron responses and licking were analyzed to investigate the afferent input pathway(s) responsible for LHA neural responses to conditioning CTSs in positive reinforcement and to identify the central site involved in CTS learning. Although the animals were restrained, there was no respiratory, cardiac rate, or blood pressure evidence of stress. The headholder was specially designed in our laboratory to avoid pain or discomfort to the animal. The subjects would often, after the first few sessions, voluntarily enter into position in the apparatus, presumably to obtain the reward available during the experiments. 2. In positive reinforcement, a rat was rewarded by 5 microliters of glucose or ICSS when it licked a spout. The rat licked for glucose after CTS1+ or for ICSS after CTS2+. In negative reinforcement, an aversive stimulus, either electric shock or tail pinch, was applied if the rat did not lick the spout. The electric shock and tail pinch were maintained weak enough to produce an avoidance ratio less than 20-30%, averaged in all trials. The rat licked to avoid electric shock after CTS1- or tail pinch after CTS2-. 3. Of 271 LHA neurons analyzed, 202 (74.5%) responded to either or both rewarding and aversive stimuli. The number of neurons that responded to only rewarding stimuli was relatively large (105/271), and the number that responded similarly to both rewarding and aversive stimuli was small (29/271). The effects of both glucose and ICSS, and the effects of both electric shock and tail pinch, were usually similar in neurons analyzed for both rewarding and aversive stimulation. Of 271 neurons, 173 responded differentially to rewarding and aversive stimuli. 4. Neural and behavioral responses were recorded before, during, and after local anesthesia of the VTA in 15 rats and of the AM in 14 rats. Injections of 0.3-0.8 microliters of 5% procaine hydrochloride or 0.9% saline were made at a rate of 0.3 microliters/min through guide cannulae chronically implanted in the VTA and AM, ipsilateral to the recording and ICSS sites in 29 rats that self-stimulated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tail pinch-induced eating: Is it the tail or the pinch?

Mildly pinching the tail of the rat results in a set of consummatory behaviors including eating, chewing and licking. This phenomenon has been characterized as one which is not causally dependent on induction of pain. In the present study we report that pinching the scruff of the neck, the ears, or the rear paw of rats also results in consummatory behaviors similar to those observed during tail pinch. We suggest that stress-induced eating caused by pressure applied to various regions of the rat involves the perception of noxious stimuli (nociception).     

Effects of electrical stimulation of the tooth pulp and phrenic nerve fibers on C1 spinal neurons in the rat

 Effects of electrical stimulation of the ipsilateral tooth pulp (TP) on C₁ spinal neurons were determined in 33 anesthetized rats. One hundred and seven neurons responded to TP stimulation. In 10 rats, the activity of 18 C₁ spinal neurons and the amplitude of a digastric electromyogram (dEMG, n=10) increased proportionally during the TP stimulation at an intensity of 1–3 times the threshold for jaw-opening reflex (JOR). Excitatory receptive somatic fields were examined in 61 neurons. Somatic field locations of many neurons (67.2%) involved the ipsilateral face, neck, and jaw. The activity of 45 neurons was increased by both noxious pinch and brushing hair. Of the 107 C₁ spinal neurons responding to TP stimulation, 55 were tested to determine the effects of electrical stimulation of the ipsilateral phrenic nerve (PN) above the heart. Twenty-eight of 55 neurons tested were excited; no change in activity was seen for the remaining 27 neurons. The activity of six neurons increased as the intensity of PN stimulation was increased. Excitatory receptive somatic fields were determined in 28 neurons, and somatic field locations of 17 neurons (60.7%) included the ipsilateral face, neck, and jaw. Both noxious pinch and brushing hair excited all 28 neurons. These results suggest that there may be the convergence of face, neck, jaw, TP, and PN afferents on the same C₁ spinal neurons in the rat. Received: 23 June 1998 / Accepted: 11 December 1998     

Clip induced analgesia and immobility in the mouse: activation by different sensory modalities

In the present study we have attempted to characterize, in mice, a situation which appears to simulate real life predation and elicits simultaneous analgesia and immobility. We utilized pinch produced by clip application to various regions of the body and examined its effect on responsiveness to noxious stimuli and motor behavior. Intense noxious clip was applied to the nape of the neck, back and base of the tail. The area most effective for the elicitation of both clip induced analgesia and immobility was the nape of the neck while tail pinch resulted in analgesia but not immobility. Evidence is provided that different systems are responsible for clip induced immobility and analgesia. Temporal dissociation of clip induced analgesia and immobility could be demonstrated with continuous clip application for 30 min showing a different time course for the analgesic and immobilizing effects. Different stimuli were effective in eliciting clip induced analgesia and immobility with noxious stimuli essential for the induction of clip induced analgesia and innocuous stimuli sufficient for clip induced immobility. Thus, low analgesic doses of local anesthetics injected into the nape of the neck prevented noxious clip from inducing analgesia but immobility was still evident. In contrast, nonnoxious pinch to the nape of the neck elicited immobility but not analgesia and clip induced immobility could still be induced after the administration of high doses of morphine which completely blocked responses to noxious stimuli. These results demonstrate that in a situation resembling natural predation both analgesia and immobility are produced concurrently but that these behavioral phenomena can be elicited differentially and may be mediated by different independent systems.