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Tail immersion test for the evaluation of a nociceptive reaction in mice. Methodological considerations.

The effect of two commonly used methods to immobilize the animals, viz. tube restrainer and wrapping in a diaper (chux) on the tail flick latency in immersion test, was evaluated in mice using a stimulus temperature of 50 degrees C. The animals were immobilized either in the tube or chux briefly (25-30 sec) during the tail flick measurements. The basal tail flick latency was 2.8 +/- 0.2 in the tube restrained and 5.5 +/- 0.3 sec in chux restrained groups (p less than 0.001). The analgesic effect of morphine (1, 3, 4, 7, and 10 mg/kg) was significantly higher in the chux-restrained animals as indicated by the dose ratio of 2.16 for the 50% analgesic response in the chux versus tube restrained mice. The tail flick latency, 15 min after naloxone injection (1 and 3 mg/kg), expressed as % of predrug latency was significantly reduced in the chux- but not the tube-restrained group. The hyperalgesic effect of naloxone could not be detected in chux-restrained animals, when the water temperature was increased to 55 degrees C. The results demonstrate that the restraining procedure will influence the analgesic effects of test drugs in tail immersion test. Furthermore, the stimulus temperature appears to be an important variant that could influence the results in this test. The present results demonstrate the hyperalgesic effect of naloxone after systemic administration in the tail immersion test and supports the concept that tail flick response is tonically inhibited by endogenous opioid systems.

Animals↗

Habituation to sham testing procedures modifies tail-flick latencies: effects on nociception rather than vasomotor tone.

Habituation of rats to the testing environment and procedures reduces flexor withdrawal latencies to those of spinalised animals. We have now recorded surface temperatures at 3 sites on the tail and tail-flick latencies simultaneously in experimentally naive (novice) rats and in habituated rats. At usual ambient temperatures (20 +/- 1 degree C), tail temperatures fluctuated in accordance with the predictions of an on-off controller. There was an inverse correlation between the tail-flick latency and the temperature at the site of noxious stimulation. A similar correlation was found when the pre-stimulus temperature of the tip of the tail was held at temperatures ranging from 21 degrees C to 35 degrees C. Habituated animals exhibited a similar linear regression slope factor but lower latencies than novice animals at each temperature. We conclude (1) that tail-flick latency is determined partly by the pre-stimulus temperature at the site of noxious thermal stimulation, and (2) that the effects of habituation on tail-flick latency are more likely to be explained by differences in nociception than in regional vasomotor tone.

Animals↗

Intracerebroventricular micro-injections of non-steroidal anti-inflammatory drugs abolish reperfusion hyperalgesia in the rat's tail.

Prostaglandins are mediators of reperfusion hyperalgesia; their site of action may be in the periphery, in the central nervous system, or both. We have investigated whether prostaglandins play a role in the central nervous system during reperfusion hyperalgesia, by intracerebroventricular (i.c.v.) micro-injection of non-steroidal anti-inflammatory drugs (NSAID), to inhibit local prostanoid synthesis. We induced tail ischaemia in conscious rats by applying an inflatable cuff at the base of the tail. The cuff was released at the first signs of co-ordinated escape behaviour. Responses to a noxious thermal stimulus were assessed, by measuring tail flick latency following immersion of the tail in water at 49 degrees C, prior to and immediately after release of the tourniquet. Tail flick latency decreased significantly following ischaemia, that is there was post-ischaemic reperfusion hyperalgesia. Intracerebroventricular micro-injection of NSAID prior to applying the tourniquet had no effect on the co-ordinated escape behaviour during ischaemia or on the tail flick latency after application of a sham tourniquet (uninflated cuff). However all the drugs abolished the hyperalgesia evident during reperfusion. Doses required to abolish hyperalgesia were 0.001 mg/kg indomethacin, 0.08 mg/kg dipyrone, 0.09 mg/kg ibuprofen, 0.2 mg/kg diclofenac sodium and 0.2 mg/kg paracetamol. These doses are 2-3 orders of magnitude less than those necessary to abolish reperfusion hyperalgesia when the same drugs are administered systemically. Our results indicate that the development of reperfusion hyperalgesia of the rat's tail depends on the synthesis of prostanoids within the central nervous system.

Animals↗

Peroxisomal enzyme activity changes in the tail of anuran tadpoles during metamorphosis.

This study attempts to clarify peroxisomal enzyme activity changes in the atrophying tail of anuran tadpoles. Changes in catalase, D-amino acid oxidase and urate oxidase activity were spectrophotometrically investigated using tadpole tails of Rana japonica and Rana nigromaculata. In R. japonica, total catalase activity decreased in tails undergoing regression during spontaneous and DL-thyroxine (T4)-induced metamorphosis, whereas total D-amino acid oxidase and urate oxidase activity increased. In R. nigromaculata, total activity of catalase decreased in tails regressing spontaneously. Total D-amino acid oxidase activity increased during advanced stages of tail regression, but total urate oxidase activity decreased. Specific activity of tadpole peroxisomal enzymes in the above two species was found to be highest for D-amino acid oxidase, followed by urate oxidase and then catalase at latter stages of normal tail regression. Atrophying tadpole tails develop a mechanism for hydrogen peroxide production, which may contribute to cell death in this organ.

Amino Acid Oxidoreductases↗

Evaluation of the tail formalin test in mice as a new model to assess local analgesic effects.

Opioids are effective topical analgesics in the radiant heat tailflick assay and display synergistic interactions with a number of other classes of drugs. To determine whether these actions extend to other types of nociception, we examined the actions of topical morphine and lidocaine in a tail formalin assay in the mouse. Formalin responses in the tail were similar to those seen in the hind paw, but were limited to licking. Unlike the traditional hind paw assay, the time-course of nociceptive behavior in the tail was monophasic; lasting 40-60 min. Morphine, MK-801 and acetylsalicylic acid (ASA) were active systemically in the tail formalin assay with potencies similar to those seen in the second phase of the paw formalin test. Both morphine and lidocaine were active topically in the tail formalin assay, although their time-course of action appeared to be shorter than that of the formalin. However, morphine displayed ceiling effect not seen when it was administered systemically. Lidocaine also had a ceiling effect. When given together, the response to the combination was supra-additive, consistent with our prior studies showing synergy in the radiant heat tailflick assay. These studies validate the formalin assay in the tail and support the topical actions of opioids and other drugs in a second pain model. They also suggest supra-additive interactions between morphine and lidocaine similar to those previously seen. The tail formalin assay will be valuable in assessing the activity of topical drugs.

Analgesics, Opioid↗

Three-dimensional rearrangement of proteins in the tail of bacteriophage T4 on infection of its host.

The contractile tail of bacteriophage T4 undergoes major structural transitions when the virus attaches to the host cell surface. The baseplate at the distal end of the tail changes from a hexagonal to a star shape. This causes the sheath around the tail tube to contract and the tail tube to protrude from the baseplate and pierce the outer cell membrane and the cell wall before reaching the inner cell membrane for subsequent viral DNA injection. Analogously, the T4 tail can be contracted by treatment with 3 M urea. The structure of the T4 contracted tail, including the head-tail joining region, has been determined by cryo-electron microscopy to 17 A resolution. This 1200 A-long, 20 MDa structure has been interpreted in terms of multiple copies of its approximately 20 component proteins. A comparison with the metastable hexagonal baseplate of the mature virus shows that the baseplate proteins move as rigid bodies relative to each other during the structural change.

Bacteriophage T4↗

Toxicity of cadmium and zinc mixtures to cercarial tail loss in Diplostomum spathaceum (Trematoda:Diplostomidae).

The effects of cadmium and zinc mixtures on tail loss of the free-living cercarial stage of the parasitic fluke Diplostomum spathaceum were investigated at concentrations ranging from 0.1 to 10,000 microg/L. Cercariae were exposed to metal mixtures of equal concentrations, metal mixtures of unequal concentrations, and a low-dose pretreatment followed by high-dose exposure mixtures. Under control conditions as the cercarial population aged tail loss occurred naturally a few hours before death, with an increasing tail loss over time associated with a decrease in cercarial survival. Under all mixture exposures the period of tail loss was prolonged compared to single-metal exposures. In most test solutions this was associated with a similar increase in survival of cercariae. Inhibition of tail loss occurred in low concentrations (0.1-100 microg/L) of equal mixed exposures. In some unequal, and in all pretreatment mixture exposures, a significant stimulation of tail loss occurred compared to the pattern of decreasing survival over time within the cercarial population. The importance of toxic metal mixtures to cercarial tail loss and potential implications for successful parasite transmission are discussed.

Animals↗

Pre-emptive ring-block with bupivacaine prevents the development of thermal hyperalgesia, but not sustained mechanical hyperalgesia, in rat tails exposed to ultraviolet A light.

UNLABELLED: We investigated the role of the C-fiber barrage in the development of hyperalgesia in rat tails exposed to ultraviolet A (UVA)-light exposure by pre-emptively blocking C-fiber activation with the local anesthetic bupivacaine. Thirty minutes before UVA-light exposure, male Sprague-Dawley rats were given subcutaneous injections, in the base of the tail, of either saline or bupivacaine (1 mL of .5%). Thermal hyperalgesia was assessed daily from day 1 to day 10 after UVA-light exposure by measuring response latency to noxious heat (tail immersion in 49 degrees C water). Injection of bupivacaine completely prevented the development of thermal hyperalgesia (P < .05, main effect of group, 2-way analysis of variance). Primary mechanical hyperalgesia was assessed daily from day 1 to day 14 after UVA-light exposure by measuring aversive behavior responses to a punctate pressure applied to the tail with a von Frey anesthesiometer. The rats given bupivacaine developed hyperalgesia to the mechanical challenge that persisted for 14 days (P < .05, main effect of time, 2-way analysis of variance) and was identical to the hyperalgesia developed by the rats given saline. We concluded that the C-fiber barrage is involved in the development of thermal hyperalgesia but not sustained primary mechanical hyperalgesia, induced by exposing rats' tails to UVA light. PERSPECTIVE: UVA-light exposure of the rat tail causes prolonged hyperalgesia to noxious thermal and mechanical challenges. We have demonstrated that the C-fiber barrage is involved in the development of sustained thermal hyperalgesia, but not mechanical hyperalgesia, caused by exposure of the rat tail to UVA light.

Analysis of Variance↗

Temporal requirement for bone morphogenetic proteins in regeneration of the tail and limb of Xenopus tadpoles.

Bone morphogenetic protein (BMP) signalling is necessary for both the development of the tail bud and for tail regeneration in Xenopus laevis tadpoles. Using a stable transgenic line in which expression of the soluble BMP inhibitor noggin is under the control of the temperature inducible hsp70 promoter, we have investigated the timing of the requirement for BMP signalling during tail regeneration. If noggin expression is induced followed by partial amputation of the tail, then wound closure and the formation of the neural ampulla occur normally but outgrowth of the regeneration bud is inhibited. Furthermore, we show that BMP signalling is also necessary for limb bud regeneration, which occurs in Xenopus tadpoles prior to differentiation. When noggin expression is induced, limb bud regeneration fails at an early stage and a stump is formed. The situation appears similar to the tail, with formation of the limb bud blastema occurring but renewed outgrowth inhibited. The transcriptional repressor Msx1, a direct target of BMP signalling with known roles in vertebrate appendage regeneration, fails to be re-expressed in both tail and limb in the presence of noggin. DNA labelling studies show that proliferation in the notochord and spinal cord of the tail, and of the blastema in the limb bud, is significantly inhibited by noggin induction, suggesting that in the context of these regenerating appendages BMP is mainly required, directly or indirectly, as a mitogenic factor.

Animals↗

Involvement of nitric oxide in development of tail-tremor induced by repeated nicotine administration in rats.

Daily administration of nicotine (0.5 mg/kg per day s.c.) to rats caused a tremor that appeared only in the tail (tail-tremor) and which became more marked over 8 days. Nitric oxide (NO) synthase inhibitors, Nw-nitro-L-arginine (10 mg/kg per day i.p.) or Nw-nitro-L-arginine methyl ester (20 and 40 mg/kg per day i.p.), administered each day before nicotine attenuated the development of the tail-tremor. However, neither Nw-nitro-L-arginine (2-10 mg/kg i.p.) nor Nw-nitro-L-arginine methyl ester (10-40 mg/kg i.p.) affected the tail-tremor that developed after 14 days of repeated nicotine administration. The noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 ((+)-5-methyl-10,11,-dihydro-5H-dibenzo[a,b]cyclohepten-5,10-imine hydrogen maleate) at 0.2 mg/kg per day (i.p.), or competitive antagonist, CPP (3-[(+/-)-2-carboxypiperazin-4-yl] propyl-1-phosphonic acid) at 2 mg/kg per day (i.p.), administered each day before nicotine attenuated the development of the tail-tremor. MK-801 (0.01-0.2 mg/kg i.p.) but not CPP (0.5-4 mg/kg i.p.) suppressed the tail-tremor that developed after 14 days of repeated nicotine administration. These results suggest that NO formation mediated by NMDA receptors is involved in the mechanisms underlying the tail-tremor induced by the repeated administration of nicotine.

Animals↗

NMDA receptor-dependent long term hyperalgesia after tail amputation in mice.

Amputation of the mouse tail tip (2.5 cm) caused long term thermal and mechanical hyperalgesia in the remaining part of the tail. Hyperalgesia of the hindpaw to noxious heat (55 degrees C) and cold (0 degrees C) stimuli were also observed. Hyperalgesia at both the tail and hindpaw had a rapid onset (< or = 30 min) and long lasting (> or = 7 days) effect. Skin temperature of the remaining tail or hindpaw was not significantly affected by the amputation. Heat injury of the tail in normal mice induced short but not long term hyperalgesia (< or = 48 h). Intrathecal pretreatment with NMDA receptor antagonists significantly attenuated long term hyperalgesia caused by tail amputation. These results strongly suggest that spinal NMDA receptors are critical for the induction of hyperalgesia by tail amputation, and the current mouse model may prove useful for investigating mechanisms of persistent pain after amputation.

2-Amino-5-phosphonovalerate↗

Laterality of tail resting posture in three species of New World primates.

A variety of mammalian species including prosimian and simian primates wrap their tails around their bodies as a means of thermoregulation and for reasons of comfort during resting or sleep. Adopting such a resting posture requires an animal to move its tail either to the right or to the left of the midline of its body, and thus to perform a lateralized behavior. The purpose of this study was to assess the occurrence of lateral biases in tail resting posture in three species of New World primates. Twenty squirrel monkeys, spider monkeys, and howler monkeys, respectively, were observed and data on tail resting posture were collected and analyzed. The results demonstrate (1) that individual squirrel monkeys and spider monkeys exhibit highly significant lateral biases in tail resting posture; (2) a lack of a lateral bias at the group level; (3) that howler monkeys fail to show side preferences in tail wrapping; (4) a lack of sex differences in this behavior in all three species; and (5) a lack of significant correlations between preferred side of tail resting posture and preferred side of hand use in simple reaching tasks which had been assessed with a subset of animals in previous studies. Thus, the present study provides evidence for a behavioral asymmetry which is well-known to occur in rats but has not been described so far in nonhuman primates, and which might offer an additional approach to the investigation of the mechanisms underlying functional cerebral asymmetries.

Alouatta↗

Human tails and pseudotails.

A case of a tail in a 2-week-old infant is reported, and findings from a review of 33 previously reported cases of true tails and pseudotails are summarized. The true, or persistent, vestigial tail of humans arises from the most distal remnant of the embryonic tail. It contains adipose and connective tissue, central bundles of striated muscle, blood vessels, and nerves and is covered by skin. Bone, cartilage, notochord, and spinal cord are lacking. The true tail arises by retention of structures found normally in fetal development. It may be as long as 13 cm, can move and contract, and occurs twice as often in males as in females. A true tail is easily removed surgically, without residual effects. It is rarely familial. Pseudotails are varied lesions having in common a lumbosacral protrusion and a superficial resemblance to persistent vestigial tails. The most frequent cause of a pseudotail in a series of ten cases obtained from the literature was an anomalous prolongation of the coccygeal vertebrae. Additional lesions included two lipomas, and one each of teratoma, chondromegaly , glioma, and a thin, elongated parasitic fetus.

Adolescent↗

Evaluation of sperm tail membrane integrity by light microscopy.

During routine evaluation of trypan blue-Giemsa stained semen smears, sperm cells can be found with unstained heads and with stained tails. It was hypothesized that these cells were immotile and should not be considered as live. Sperm motility was determined in isoosmotic, and presumably isotonic trypan blue-stained wet preparations. Bull, ram and boar semen smears were stained with hypoosmotic trypan blue-Giemsa to compare the relationship between the percentage of stained sperm tails and the percentage of sperm tails remaining straight under hypoosmotic conditions. Actively moving spermatozoa with unstained heads, but with stained tails were never observed in wet preparations. The correlation coefficient found between the percentage of sperm with stained tails and the percentage with straight tails was 0.81, 0.94 and 0.85 for bull, ram and boar spermatozoa, respectively. Results of this study show that sperm cells with an intact head membrane, but a stained and presumably membrane-damaged tail are not motile. Therefore these cells should be included in the dead category rather than alive in the usual live-dead studies with vital stains.

Animals↗

Tail artery blood flow measured by chronically implanted Doppler ultrasonic probes in unrestrained conscious rats.

We describe a surgical procedure for chronically implanting a Doppler ultrasonic probe around the tail artery of the rat to measure phasic flow velocity in the tail artery of the unrestrained conscious rat. The phasic tail flow signal is highly correlated with the simultaneously recorded superior mesenteric flow signal (range 0.70-0.89 in seven rats) during vasoconstriction induced by exposure to formaldehyde vapour. In response to two quick alerting taps on the cage, tail flow velocity fell from 20+/-2 to 7+/-1 cm/s (P<0.01) and mesenteric flow fell from 30+/-5 to 25+/-4 cm/s (P<0.05), with the fall in tail flow being significantly greater than the fall in mesenteric flow (P<0.05, n=7 rats). In anesthetized rats, the phasic tail flow signal was highly correlated with phasic arterial pressure (range 0.71-0.83 in seven rats). The ability to reliably measure phasic arterial tail flow in the conscious unrestrained rat should facilitate experimental studies of brain pathways regulating flow to this principally cutaneous vascular bed in different physiological situations.

Animals↗

Do reactive oxygen species underlie the mechanism of apoptosis in the tadpole tail?

Although "programmed cell death" has been postulated to underlie the mechanism for the disappearance of the tadpole tail, critical factors that trigger this phenomenon remain to be elucidated. To investigate the mechanism for the disappearance of the tail, changes in morphology, DNA status and the enzymes which metabolize reactive oxygen species were determined in the tail of Rana rugosa tadpoles. Histological examination revealed that apoptotic cell death was apparent in the tail myocytes during metamorphosis. Electrophoretic analysis of the tail DNA revealed a marked fragmentation. During the apoptotic changes, the activity of Cu/Zn-type superoxide dismutase (SOD) in the tail markedly increased with a concomitant decrease in its catalase activity. The apoptotic process was markedly enhanced by adding hydrogen peroxide (H2O2) and aminotriazole, a catalase inhibitor, to the medium. These observations suggested that apoptotic cell death in the tadpole tail might be triggered, at least in part, by a mechanism depending on active oxygen species, such as H2O2.

Amitrole↗

Energetic costs of tail loss in a montane scincid lizard.

Most species of lizards will shed their tails at the point of contact when grasped by a predator. We investigated the energetic consequences of tail loss by measuring lipids in a scincid lizard that stores energy in its tail for reproduction. Most of the lipids were concentrated in the proximal portion of the tail. Thus, partial tail loss may not severely affect energy stores if the distal portion of the tail is shed in predatory encounters. We also found that the width of the tail was a reliable non-invasive index of energy reserves in this species.

Animals↗

Alpha-1D adrenoceptors are involved in reserpine-induced supersensitivity of rat tail artery.

1. We examined reserpine-induced chemical denervation supersensitivity with special reference to alpha-1 adrenoceptor (AR) subtypes. 2. Chronic treatment with reserpine for 2 weeks depleted noradrenaline in the tail artery and spleen of rats. Noradrenaline in the thoracic aorta was negligible before and after reserpine treatment. 3. The treatment with reserpine produced supersensitivity in the contractile responses of the rat tail artery to phenylephrine, 5-HT and KCl, resulting in leftward shift of concentration-response curves (11.6-, 2.5- and 1.1-fold at EC(50) value, respectively). These results suggest a predominant sensitization of the alpha-1 AR-mediated response by reserpine treatment. 4. BMY 7378 at a concentration (30 nm) specific for blocking the alpha-1D AR subtype, but not KMD-3213 at a concentration (10 nm) selective for blocking the alpha-1A AR subtype, inhibited the supersensitivity of the phenylephrine-induced response in the reserpine-treated artery. On the other hand, the response to phenylephrine in reserpine-untreated artery was selectively inhibited by the same concentration of KMD-3213, but not by BMY 7378. Prazosin, a subtype-nonselective antagonist, blocked the responses to phenylephrine with the same potency, regardless of reserpine treatment. 5. In the thoracic aorta and spleen, no supersensitivity was produced in the responses to phenylephrine by reserpine treatment. 6. In a tissue segment-binding study using [(3)H]-prazosin, the total density and affinity of alpha-1 ARs in the rat tail artery were not changed by treatment with reserpine. However, alpha-1D AR with high affinity for BMY 7378 was significantly detected in reserpine-treated tail artery, in contrast to untreated artery. Decreases in alpha-1A AR with high affinity for KMD-3213 and alpha-1B AR with low affinities for KMD-3213 and BMY 7378 were also estimated in reserpine-treated tail artery. 7. Alpha-1D AR mRNA in rat tail artery increased to three-folds by reserpine treatment, whereas the levels of alpha-1A and 1B mRNAs were not significantly changed. 8. The present results suggest that chronic treatment with reserpine affects the expression of alpha-1 AR subtypes of rat tail artery and that the induction of alpha-1D ARs with high affinity for catecholamines is in part associated with reserpine-induced supersensitivity.

Animals↗