Rodent Tail Research Articles

The Evolution of Rodent Tail Morphology.

AbstractPopulation-level variation in rodent tail structures has been variously attributed to facilitating social communication, locomotion, thermoregulation, and predator avoidance. Little is known, however, about the applicability of these ecological and social correlates to explaining the tremendous interspecific diversity of this appendage. To investigate the potential drivers of rodent tail morphology at a macroevolutionary level, we first carefully reviewed the literature and constructed a list of major hypotheses regarding this variation. We then compiled a database of 11 different tail traits related to length, color, texture, and ecological characteristics for 2,101 species of rodents (order Rodentia) and examined their key evolutionary correlates. Using Bayesian phylogenetic mixed models across the entire order and additionally within the five rodent suborders, we found that tail length is correlated with both temperature (Allen's rule) and locomotory mode, that black tips are more common in brightly lit environments, that naked tails are often found in warmer climates, that fluffy-tipped tails are more common in smaller and/or arboreal species, that prehensility is predominant in arboreal species and/or species with longer tails, and that tail autotomy is more common in open environments. Most of our tested predictions, largely drawn from population-level studies, are not recapitulated across the entire order, potentially indicating a role of local ecological context in shaping tail morphology.

Novel GluN2B-Selective NMDA Receptor Negative Allosteric Modulator Possesses Intrinsic Analgesic Properties and Enhances Analgesia of Morphine in a Rodent Tail Flick Pain Model.

Many cases of accidental death associated with drug overdose are due to chronic opioid use, tolerance, and addiction. Analgesic tolerance is characterized by a decreased response to the analgesic effects of opioids, requiring increasingly higher doses to maintain the desired level of pain relief. Overactivation of GluN2B-containing N-methyl-d-Aspartate receptors is thought to play a key role in mechanisms underlying cellular adaptation that takes place in the development of analgesic tolerance. Herein, we describe a novel GluN2B-selective negative allosteric modulator, EU93-108, that shows high potency and brain penetrance. We describe the structural basis for binding at atomic resolution. This compound possesses intrinsic analgesic properties in the rodent tail immersion test. EU93-108 has an acute and significant anodyne effect, whereby morphine when combined with EU93-108 produces a higher tail flick latency compared to that of morphine alone. These data suggest that engagement of GluN2B as a target has utility in the treatment of pain, and EU93-108 could serve as an appropriate tool compound to interrogate this hypothesis. Future structure-activity relationship work around this scaffold could give rise to compounds that can be co-administered with opioids to diminish the onset of tolerance due to chronic opioid use, thereby modifying their utility.

Dopamine in the rodent tail of striatum regulates behavioral variability in response to threatening novel objects

Mice display variability in fear-like responses to many external salient events, such as encountering unexpected novel objects, but the neural basis of this variability has been unclear. Akiti etal. (2022) demonstrate that dopamine in the tail of the rodent striatum predicts and regulates salience-related variability in individuals' behavioral responses to unexpected novel objects.

A Novel Rat Tail Needle Minimally Invasive Puncture Model Using Three-Dimensional Printing for Disk Degeneration and Progressive Osteogenesis Research.

Many studies focused on the annulus fibrosus (AF) injury in rodent tail model for the intervertebral disk degeneration (IDD) research. However, previous studies caused tremendous injury of intervertebral disk (IVD) by penetrating whole disk. This study aimed to build a progressive IDD rodent tail model by a novel device for precise and minimally invasive puncture in AF. A precise puncture device was customized by 3D Printing Technique. 40 rodent tail IVDs were randomly grouped as follows: group A, non-puncture; group B, annulus needle puncture (ANP) for 4 week; group C, ANP for 8 week; and group D, ANP for 12 week. Pre- and post-puncture IVD height on radiographs and IVD signal intensity on T2 magnetic resonance imaging (MRI) were measured. Average bone density (ABD) on the end of coccygeal vertebrae between punctured disk was measured on the radiographs. Hematoxylin and eosin, TUNEL staining methods, immunofluorescence for cleaved-caspas3 and immunohistochemistry for aggrecan and collagen II were performed. Progressively and significantly increasing IVD height loss and degenerative grade were observed following the time points. The ABD was respectively, 81.20 ± 4.63 in group A, 83.93±3.18 in group B, 92.65 ± 4.32 in group C, 98.87 ± 6.69 in group D. In both group C and group D, there were significant differences with group A. In histology, increasing number of AF cells was noted in group B. In both group C and D, the fissures in AF were obviously observed, and a marked reduction of AF cells were also observed. In all ANP groups, there were significant decrease in number of NP cells, as well as aggrecan and collagen II contents. TUNEL assay showed cellular apoptosis were stimulated in all puncture group, especially in group D. A progressive IDD rat model could be standardly established by the micro-injury IVD puncture using a novel 3D printing device. This animal model provided a potential application for research of progressive hyperosteogeny following IDD development.

Controlled Dynamic Spine Distraction Increases Vertebral Body Growth, Disc Height and Volume, and Nucleus Pulposus Expansion; An in Vivo Study on Rodent Tail Model

Controlled Dynamic Spine Distraction Increases Vertebral Body Growth, Disc Height and Volume, and Nucleus Pulposus Expansion; An in Vivo Study on Rodent Tail Model

Shape Feature Extraction Methods of Rodents in the Field Based on Machine Vision

In order to obtain the shape features of rodents from the field, a feature extraction scheme based on machine vision was proposed. We design an experimental device with a camera. The camera placed on the top of the device to get the rodent image. After thresholding rodent image based on the global value, we get the binary image, and then the morphological erosion and dilation operation are used to denoise, and the contour are detected by the 8 adjacent pixels of a point. Chain code analysis method is used to track the contour. Multi-contour tracking extraction method is used to remove the non-rodent region. Based on the shape of the rodent tail that is slenderer than the body, we split the rodent’s tail from the body on the precise contour image. The length of the tail, the length of the body, the height of the body, the proportions of the tail and the body are extract based on contour analysis. Experiments show that this method can extract shape features of rodents accurately. It can provide basic data for analyzing the life habits and population evolution of field rodents.

Total disc replacement using tissue-engineered intervertebral discs in the canine cervical spine.

The most common reason that adults in the United States see their physician is lower back or neck pain secondary to degenerative disc disease. To date, approaches to treat degenerative disc disease are confined to purely mechanical devices designed to either eliminate or enable flexibility of the diseased motion segment. Tissue engineered intervertebral discs (TE-IVDs) have been proposed as an alternative approach and have shown promise in replacing native IVD in the rodent tail spine. Here we demonstrate the efficacy of our TE-IVDs in the canine cervical spine. TE-IVD components were constructed using adult canine annulus fibrosis and nucleus pulposus cells seeded into collagen and alginate hydrogels, respectively. Seeded gels were formed into a single disc unit using molds designed from the geometry of the canine spine. Skeletally mature beagles underwent discectomy with whole IVD resection at levels between C3/4 and C6/7, and were then divided into two groups that received only discectomy or discectomy followed by implantation of TE-IVD. Stably implanted TE-IVDs demonstrated significant retention of disc height and physiological hydration compared to discectomy control. Both 4-week and 16-week histological assessments demonstrated chondrocytic cells surrounded by proteoglycan-rich matrices in the NP and by fibrocartilaginous matrices in the AF portions of implanted TE-IVDs. Integration into host tissue was confirmed over 16 weeks without any signs of immune reaction. Despite the significant biomechanical demands of the beagle cervical spine, our stably implanted TE-IVDs maintained their position, structure and hydration as well as disc height over 16 weeks in vivo.

The effects of misalignment during in vivo loading of bone: Techniques to detect the proximity of objects in three-dimensional models

Theories of mechanical adaptation of bone suggest that mechanical loading causes bone formation at discrete locations within bone microstructure experiencing the greatest mechanical stress/strain. Experimental testing of such theories requires in vivo loading experiments and high-resolution finite element models to determine the distribution of mechanical stresses. Finite element models of in vivo loading experiments typically assume idealized boundary conditions with applied load perfectly oriented on the bone, however small misalignments in load orientation during an in vivo experiment are unavoidable, and potentially confound the ability of finite element models to predict locations of bone formation at the scale of micrometers. Here we demonstrate two different three-dimensional spatial correlation methods to determine the effects of misalignment in load orientation on the locations of high mechanical stress/strain in the rodent tail loading model. We find that, in cancellous bone, the locations of tissue with high stress are maintained under reasonable misalignments in load orientation (p<0.01). In cortical bone, however, angular misalignments in the dorsal direction can alter the locations of high mechanical stress, but the locations of tissue with high stress are maintained under other misalignments (p<0.01). We conclude that, when using finite element models of the rodent tail loading model, small misalignments in loading orientation do not affect the predicted locations of high mechanical stress within cancellous bone.

Minimally invasive method for determining the effective lymphatic pumping pressure in rats using near-infrared imaging

The ability to quantify collecting vessel function in a minimally invasive fashion is crucial to the study of lymphatic physiology and the role of lymphatic pump function in disease progression. Therefore, we developed a highly sensitive, minimally invasive research platform for quantifying the pumping capacity of collecting lymphatic vessels in the rodent tail and forelimb. To achieve this, we have integrated a near-infrared lymphatic imaging system with a feedback-controlled pressure cuff to modulate lymph flow. After occluding lymphatic flow by inflating a pressure cuff on the limb or tail, we gradually deflate the cuff while imaging flow restoration proximal to the cuff. Using prescribed pressure applications and automated image processing of fluorescence intensity levels in the vessels, we were able to noninvasively quantify the effective pumping pressure (P(eff), pressure at which flow is restored after occlusion) and vessel emptying rate (rate of fluorescence clearance during flow occlusion) of lymphatics in the rat. To demonstrate the sensitivity of this system to changes in lymphatic function, a nitric oxide (NO) donor cream, glyceryl trinitrate ointment (GTNO), was applied to the tails. GTNO decreased P(eff) of the vessels by nearly 50% and the average emptying rate by more than 60%. We also demonstrate the suitability of this approach for acquiring measurements on the rat forelimb. Thus, this novel research platform provides the first minimally invasive measurements of P(eff) and emptying rate in rodents. This experimental platform holds strong potential for future in vivo studies that seek to evaluate changes in lymphatic health and disease.

Differential transport function of lymphatic vessels in the rat tail model and the long-term effects of Indocyanine Green as assessed with near-infrared imaging

Introduction: Near-infrared (NIR) imaging has emerged as a novel imaging modality for assessing lymphatic function in vivo. While the technique has provided quantitative data previously unavailable, questions remain in regards to the spatiotemporal capabilities of the approach. We address three of the more important issues here using the rodent tail, one of the most widely utilized in vivo model systems in the lymphatic literature. Specifically we demonstrate (1) the transient vs. steady state response of lymphatics to tracer injection, (2) the functional characteristics of multiple collecting vessels draining the same tissue space in parallel, and (3) the long-term consequences of fluorescent tracers on lymphatic function to repeated functional measurements.Methods: Rat tails were imaged with NIR and metrics of function were calculated for both collecting vessels that drain the tail. A nitric oxide donor cream (GTNO) was applied to the tail. Additionally, two different NIR dyes, indocyanine green (ICG) and LI-COR IRDye 800CW PEG, were utilized for function imaging at the time of initial injection and at 1, 2, and 4 week follow-up time points after which both draining lymph nodes were harvested.Results and Discussion: Significant differences were found between the two collecting vessels such that the vessel first showing fluorescence (dominant) produced enhanced functional metrics compared to the second vessel (non-dominant). GTNO significantly reduced lymphatic function in the non-dominant vessel compared to the dominant. ICG remained visible in the tail for 2 weeks after injection and was accompanied by significant losses in lymphatic function and enlarged draining lymph nodes. The Licor tracer also remained visible for 2 weeks. However, the dye produced significantly lower effects on lymphatic function than ICG, and lymph nodes were not enlarged at any time point, suggesting that this may be a more appropriate contrast agent for longitudinal lymphatic imaging.

A dynamic model of circadian rhythms in rodent tail skin temperature for comparison of drug effects

Menopause-associated thermoregulatory dysfunction can lead to symptoms such as hot flushes severely impairing quality of life of affected women. Treatment effects are often assessed by the ovariectomized rat model providing time series of tail skin temperature measurements in which circadian rhythms are a fundamental ingredient. In this work, a new statistical strategy is presented for analyzing such stochastic-dynamic data with the aim of detecting successful drugs in hot flush treatment. The circadian component is represented by a nonlinear dynamical system which is defined by the van der Pol equation and provides well-interpretable model parameters. Results regarding the statistical evaluation of these parameters are presented.

Novel β-carboline-tripeptide conjugates attenuate mesenteric ischemia/reperfusion injury in the rat

We have synthesized a series of new β-carboline-tripeptide conjugates, and examined their anti-inflammatory properties in a mouse model of xylene-induced ear edema. The analgesic capacity of these compounds was further evaluated in a rodent tail flick assay. Our results indicate that β-carboline conjugate 4a manifests potent anti-inflammatory and analgesic activity while exerting a protective effect against mesenteric ischemia/reperfusion (I/R) injury in the rat.

Loss of STAT1 is associated with increased aortic rupture in an experimental model of aortic dissection and aneurysm formation

Transcription factor signal transducer and activator of transcription (STAT) 1 has been linked to a variety of pathologic states involved with matrix remodeling, but its role in aortic pathology has not been previously described. The current study hypothesized that STAT1 regulates aneurysmal degeneration and its role was evaluated in human abdominal aortic aneurysm (AAA) and in a mouse model of aortic dissection. Apolipoprotein E knockout mice (ApoE-/-) or ApoE/STAT1 double knockout mice (ApoE/STAT1-/-) were infused with 1000 ng/kg/min of angiotensin II. Systolic blood pressure (SBP) was measured in the rodent tail. At sacrifice, aortic diameters and extent of aneurysm formation were measured by digital microscopy. STAT1 and phosphorylated-STAT1 protein levels were assessed in ApoE-/- mice at 0, 7, 14, and 28 days (n = 8/time point) by enzyme-linked immunosorbent assay. Histology was performed using hematoxylin and eosin (H&E) and Movat stains. Statistical analyses included chi(2) test, t test, and analysis of variance. STAT1 messenger RNA and total protein were greater in human AAA vs non-AAA controls. In addition, aneurysms occurred in 8%, 50%, and 80% of ApoE-/- mice at 7, 14, and 28 days, respectively. Total STAT1 levels were not altered during the course of angiotensin II infusion. Phosphorylated STAT1 levels peaked at 7 days with a 1.4-fold increase over baseline (P < .05). Aneurysms occurred in 0%, 100%, and 100% of ApoE/STAT1-/- mice at 3, 5, and 28 days. In mice infused with angiotensin II for >3 days, aortic rupture occurred more frequently in ApoE/STAT-/- mice (53% vs 19%, P < .05) and at earlier time points (4.0 +/- 0.5 vs 9.2 +/- 0.77 days, P < .05) vs ApoE-/- mice. SBP did not differ between the groups during angiotensin II infusion. By 28 days, aneurysms were larger in ApoE/STAT1-/- mice compared with ApoE-/- mice (2.7 +/- 0.4 vs 1.9 +/- 0.1 mm, P < .05) and were more extensive. H&E and Movat stain did not reveal differences in aortic wall structural content at baseline between ApoE-/- and ApoE/STAT1-/- mice. Both groups demonstrated equal disorganization in the aneurysmal state. Phosphorylated STAT1 is elevated during aneurysmal degeneration. Its loss is associated with a higher rate of acute aortic rupture and more extensive aneurysms in a mouse model of aortic dissection. Further investigation is necessary to determine whether these observations are secondary to an underlying aortic wall abnormality or alterations in vessel wall matrix remodeling.

Complex polarization ratio to determine polarization properties of anisotropic tissue using polarization-sensitive optical coherence tomography

Complex polarization ratio (CPR) in materials with birefringence and biattenuance is shown as a logarithmic spiral in the complex plane. A multi-state Levenberg-Marquardt nonlinear fitting algorithm using the CPR trajectory collected by polarization sensitive optical coherence tomography (PS-OCT) was developed to determine polarization properties of an anisotropic scattering medium. The Levenberg-Marquardt nonlinear fitting algorithm using the CPR trajectory is verified using simulated PS-OCT data with speckle noise. Birefringence and biattenuance of a birefringent film, ex-vivo rodent tail tendon and in-vivo primate retinal nerve fiber layer were determined using measured CPR trajectories and the Levenberg-Marquardt nonlinear fitting algorithm.

Early Increased MT1-MMP Expression and Late MMP-2 and MMP-9 Activity during Angiotensin II Induced Aneurysm Formation

Angiotensin II (Ang II) is associated with a variety of cardiovascular diseases including aneurysm formation. The aim of this study was to evaluate the temporal changes in MT1-matrix metalloproteinase (MMP) and MMP-2 and -9 expression and activity during the course of Ang II induced experimental aneurysm formation. Apolipoprotein E knockout mice (ApoE null) were infused with either 1000 ng/kg/min of Ang II (n = 20) or saline (n = 20) and then sacrificed at 7, 14, 21, and 28 days of infusion (n = 5/group/strain). Aortic diameters were measured by digital microscopy. Systolic blood pressure (SBP) was measured in the rodent tail. Suprarenal abdominal aortas had MT1-MMP mRNA levels and MMP-2 and MMP-9 mRNA levels and activity quantitated using reverse transcriptase-polymerase chain reaction (rt-PCR) and gelatin zymography, respectively. Statistical analyses included nonpaired t-test, Fisher's exact test, and analysis of variance (ANOVA). Aneurysms occurred in 40, 40, 20, and 80% of ApoE null-Ang II mice at 7, 14, 21, and 28 days, respectively. An early and significant rise in MT1-MMP mRNA occurred in ApoE null mice infused with Ang II mice, while there was no significant change in MMP-2 or MMP-9 mRNA levels. Total MMP-2 and MMP-9 activity increased over time in ApoE null mice infused with Ang II, peaking at 28 days (ANOVA, P < 0.01). SBP was significantly elevated by 7 days in ApoE null mice infused with Ang II compared to ApoE null mice infused with saline (123 +/- 16 versus 102 +/- 6 mm Hg, P < 0.05). Angiotensin II induces an early increase in aortic MT1-MMP expression with a subsequent increase in MMP-2 and MMP-9 activity. The process by which these changes cause aneurysm formation warrants further investigation.

Differential geometry of normalized Stokes vector trajectories in anisotropic media

Trajectory of the normalized Stokes vector on the Poincaré sphere corresponding to light propagation in anisotropic tissues with birefringence and biattenuance is derived. Analytic expressions are determined from the Serret-Frenet formulas and derivatives of arc length for five quantities including the tangent, normal, and binormal vectors with curvature and torsion. Depth variation of curvature and torsion of normalized Stokes vector trajectories corresponding to light propagating in rodent tail tendon are given. Use of analytic expressions for depth variation of curvature and torsion of the normalized Stokes vector trajectories on the Poincaré sphere is discussed for analysis of polarization-sensitive optical coherence tomography data recorded from anisotropic biological tissues with birefringence and biattenuance.

Role of endplates in contributing to compression behaviors of motion segments and intervertebral discs

The purpose of this study was to gain an improved understanding of the mechanical behavior of the intervertebral disc in the presence and absence of the vertebral endplates. Mechanical behaviors of rat caudal motion segments, vertebrae and isolated disc explants under two different permeability conditions were investigated and viscoelastic behaviors were evaluated using a stretched-exponential function to describe creep and recovery behaviors. The results demonstrated that both vertebrae and discs underwent significant deformations in the motion segment even under relatively low-loading conditions. Secondly, disruption of the collagenous network had minimal impact on equilibrium deformations of disc explants as compared to disc deformations occurring in the motion segments provided that vertebral deformations were accounted for; however, differences in endplate permeability conditions had a significant effect on viscoelastic behaviors. Creep occurred more quickly than recovery for motion segment and explant specimens. In addition, disc explants and motion segments both exhibited non-recoverable deformations under axial compression under low- and high-loading conditions. Results have important implications for interpreting the role of vertebral endplates in contributing to disc mechanical behaviors and direct application to mechanobiology studies involving external loading to rodent tail intervertebral discs.

Dependence of Mechanical Behavior of the Murine Tail Disc on Regional Material Properties: A Parametric Finite Element Study

In vivo rodent tail models are becoming more widely used for exploring the role of mechanical loading on the initiation and progression of intervertebral disc degeneration. Historically, finite element models (FEMs) have been useful for predicting disc mechanics in humans. However, differences in geometry and tissue properties may limit the predictive utility of these models for rodent discs. Clearly, models that are specific for rodent tail discs and accurately simulate the disc's transient mechanical behavior would serve as important tools for clarifying disc mechanics in these animal models. An FEM was developed based on the structure, geometry, and scale of the mouse tail disc. Importantly, two sources of time-dependent mechanical behavior were incorporated: viscoelasticity of the matrix, and fluid permeation. In addition, a novel strain-dependent swelling pressure was implemented through the introduction of a dilatational stress in nuclear elements. The model was then validated against data from quasi-static tension-compression and compressive creep experiments performed previously using mouse tail discs. Finally, sensitivity analyses were performed in which material parameters of each disc subregion were individually varied. During disc compression, matrix consolidation was observed to occur preferentially at the periphery of the nucleus pulposus. Sensitivity analyses revealed that disc mechanics was greatly influenced by changes in nucleus pulposus material properties, but rather insensitive to variations in any of the endplate properties. Moreover, three key features of the model-nuclear swelling pressure, lamellar collagen viscoelasticity, and interstitial fluid permeation-were found to be critical for accurate simulation of disc mechanics. In particular, collagen viscoelasticity dominated the transient behavior of the disc during the initial 2200 s of creep loading, while fluid permeation governed disc deformation thereafter. The FEM developed in this study exhibited excellent agreement with transient creep behavior of intact mouse tail motion segments. Notably, the model was able to produce spatial variations in nucleus pulposus matrix consolidation that are consistent with previous observations in nuclear cell morphology made in mouse discs using confocal microscopy. Results of this study emphasize the need for including nucleus swelling pressure, collagen viscoelasticity, and fluid permeation when simulating transient changes in matrix and fluid stress/strain. Sensitivity analyses suggest that further characterization of nucleus pulposus material properties should be pursued, due to its significance in steady-state and transient disc mechanical response.

Mechanical differences between lumbar and tail discs in the mouse

The mouse lumbar and tail discs are both used as models to study disc degeneration; however, the mechanical behavior of these two levels has not been compared. The objective of this study was to compare the elastic and viscoelastic mechanical properties of lumbar and tail discs of the mouse under axial compression–tension loading. We hypothesized that tail discs would have a larger transition zone (e.g., neutral zone) and would be less stiff in compression. To test these hypotheses, lumbar and tail bone–disc–bone motion segments were loaded in axial compression and tension. The nonlinear elastic mechanical behavior was examined using a tri-linear curvefit. Elastic behavior of lumbar and tail discs was most different in the low-stiffness transition region (neutral zone), where lumbar discs were nearly twice as stiff over half the axial displacement. In addition, viscoelastic behavior, which was examined using a stretch–exponential curvefit, also showed large lumbar and tail differences, where lumbar discs compressed by 60% of their original height and tail discs by 98% after static creep compression. These results demonstrate that tail discs undergo far more axial displacement than lumbar discs under the same load. These findings are relevant to rodent tail models where chronic loads are applied in vivo to study mechanical pathways of degeneration. Furthermore, the tri-linear model, used here to curvefit the nonlinear compression–tension data, quantified stiffness in the transition zone for the first time, which may prove useful in future disc mechanical studies.

A novel radiant heat test for assessing pain threshold in human subjects: Measurement stability

New methodologies to assess analgesic response in humans are needed to better integrate preclini­ cal and clinical data. In the present study we examined the test-retest stability of an innovative radi­ ant heat methodology compared with an electrical stimulation methodology. For the radiant heat task, a modified rodent tail flick apparatus was used, The latency for fmger withdrawal was recorded. For the electrical stimulation tasks, subjects placed two fingers on two electrodes from which they received a brief series of increasingly intense electrical stimulations. Maximum stimulus intensity (in milliamps) delivered was recorded. On each of 4 test days, the subjects received five test trials with a lO-min in­ terval between trials. Allthe subjects were tested twice on eachapparatus in a counterbalanced design. Finger withdrawal latencies for the radiant heat task did not differ significantly across test trials or test days. Finger withdrawal scores for electrical stimulation increased significantly across test trials as well as test days. These data show that the radiant heat method generates consistent latencies across trials and days, whereas shock produces trends over time. The radiant heat task, which is convenient to operate and inexpensive to build, appears promising as a reliable test of pain threshold in humans. Many attempts have been made to develop a simple and reliable laboratory method to assess pain thresholds in human volunteers. Some ofthese methods include ice water hand immersion, thermal heat, electrical stimula­ tion, and skin pressure tests (Chery-Croze, 1983; Collier, Mehta, & Spear, 1990; Harris & Rollman, 1983). Among these different stimuli, thermal heat and electrical stim­ ulation have been chiefly used to induce experimental pain (Chery-Croze, 1983). Additionally, these methods have been frequently used in nonclinical studies in which repeated exposure to the stimulus is often required. How­ ever, considerable variation in pain threshold values have been reported with electrical stimulation. For instance, Collier et a1. reported significant variation in threshold responses following repeated exposure to electrical stim­ ulation. This may be due to a developed tolerance or adaptation that may occur over time to the sensations pro­ duced by electrical stimulation. Additionally, Harris and Rollman reported that electrical stimulation is often ac­ companied by subjective reports of anxiety and stress. Hence, the psychological components associated with electrical stimulation may lead to variability in responding. Thermal heat tests have been successfully used to de­ termine pain threshold in human volunteers for the last three decades (Hardy, Goodell, & Wolff, 1952). The two most commonly employed methods of delivering ther­ mal heat are radiant heat (use ofa beam of light or laser pulse) and conducted heat (use of Peltier thermodes on