Benoist, Jean-Michel
Pincedé, Ivanne
Ballantyne, Kay
Plaghki, Léon
[UCL]
Le Bars, Daniel
BACKGROUND: The quantitative end-point for many behavioral tests of nociception is the reaction time, i.e. the time lapse between the beginning of the application of a stimulus, e.g. heat, and the evoked response. Since it is technically impossible to heat the skin instantaneously by conventional means, the question of the significance of the reaction time to radiant heat remains open. We developed a theoretical framework, a related experimental paradigm and a model to analyze in psychophysical terms the "tail-flick" responses of rats to random variations of noxious radiant heat. METHODOLOGY/PRINCIPAL FINDINGS: A CO(2) laser was used to avoid the drawbacks associated with standard methods of thermal stimulation. Heating of the skin was recorded with an infrared camera and was stopped by the reaction of the animal. For the first time, we define and determine two key descriptors of the behavioral response, namely the behavioral threshold (Tbeta) and the behavioral latency (Lbeta). By employing more than one site of stimulation, the paradigm allows determination of the conduction velocity of the peripheral fibers that trigger the response (V) and an estimation of the latency (Ld) of the central decision-making process. Ld (approximately 130 ms) is unaffected by ambient or skin temperature changes that affect the behavioral threshold (approximately 42.2-44.9 degrees C in the 20-30 degrees C range), behavioral latency (<500 ms), and the conduction velocity of the peripheral fibers that trigger the response (approximately 0.35-0.76 m/s in the 20-30 degrees C range). We propose a simple model that is verified experimentally and that computes the variations in the so-called "tail-flick latency" (TFL) caused by changes in either the power of the radiant heat source, the initial temperature of the skin, or the site of stimulation along the tail. CONCLUSIONS/SIGNIFICANCE: This approach enables the behavioral determinations of latent psychophysical (Tbeta, Lbeta, Ld) and neurophysiological (V) variables that have been previously inaccessible with conventional methods. Such an approach satisfies the repeated requests for improving nociceptive tests and offers a potentially heuristic progress for studying nociceptive behavior on more firm physiological and psychophysical grounds. The validity of using a reaction time of a behavioral response to an increasing heat stimulus as a "pain index" is challenged. This is illustrated by the predicted temperature-dependent variations of the behavioral TFL elicited by spontaneous variations of the temperature of the tail for thermoregulation.
- Wang Haibin, Woolf Clifford J., Pain TRPs, 10.1016/j.neuron.2005.03.011
- JC Falmagne (1985)
- RD Luce (1986)
- L Plaghki, Curr Opin Investig Drugs, 6, 58 (2005)
- JA Stolwijk, J Appl Physiol, 20, 1006 (1965)
- Fleischer E., Handwerker H.O., Joukhadar S., Unmyelinated nociceptive units in two skin areas of the rat, 10.1016/0006-8993(83)91041-7
- Handwerker H.O., Anton F., Reeh P.W., Discharge patterns of afferent cutaneous nerve fibers from the rat's tail during prolonged noxious mechanical stimulation, 10.1007/bf00235972
- Danneman Peggy J., Kiritsy-Roy Judith A., Morrow Thomas J., Casey Kenneth L., Central delay of the laser-activated rat tail-flick reflex : , 10.1016/0304-3959(94)90183-x
- RH LaMotte, Fed Proc, 42, 2548 (1983)
- RH LaMotte, J Neurosci, 2, 765 (1982)
- Treede R D, Meyer R A, Raja S N, Campbell J N, Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin., 10.1113/jphysiol.1995.sp020619
- Campbell James N., Meyer Richard A., Mechanisms of Neuropathic Pain, 10.1016/j.neuron.2006.09.021
- de Jesus P. V., Hausmanowa-Petrusewicz I., Barchi R. L., The effect of cold on nerve conduction of human slow and fast nerve fibers, 10.1212/wnl.23.11.1182
- AS Paintal, 19 (1973)
- Paintal A. S., A comparison of the nerve impulses of mammalian non-medullated nerve fibres with those of the smallest diameter medullated fibres, 10.1113/jphysiol.1967.sp008376
- Franz D. N., Iggo A., Conduction failure in myelinated and non-myelinated axons at low temperatures, 10.1113/jphysiol.1968.sp008656
- Tillman D B, Treede R D, Meyer R A, Campbell J N, Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: estimates of receptor depth and threshold., 10.1113/jphysiol.1995.sp020766
- Mitchell D., Hellon R. F., Neuronal and Behavioural Responses in Rats During Noxious Stimulation of the Tail, 10.1098/rspb.1977.0064
- Necker R., Hellon R. F., Noxious thermal input from the rat tail: Modulation by descending inhibitory influences : , 10.1016/0304-3959(77)90135-x
- Ness T.J., Gebhart G.F., Centrifugal modulation of the rat tail flick reflex evoked by graded noxious heating of the tail, 10.1016/0006-8993(86)90139-3
- E Carstens, J Neurophysiol, 70, 630 (1993)
- Kawakita Kenji, Funakoshi Masaya, A quantitative study on the tail flick test in the rat, 10.1016/0031-9384(87)90015-1
- Tsuruoka Masayoshi, Matsui Aiko, Matsui Yoichiro, Quantitative relationship between the stimulus intensity and the response magnitude in the tail flick reflex, 10.1016/0031-9384(88)90101-1
- MN Carroll, Arch Int Pharmacodyn Ther, 123, 48 (1959)
- FR Granat, Arch Int Pharmacodyn Ther, 205, 52 (1973)
- MF Ren, Chin Med J, 92, 576 (1979)
- Levine Jon D., Murphy Dennis T., Seidenwurm David, Cortez Anne, Fields Howard L., A study of the quantal (all-or-none) change in reflex latency produced by opiate analgesics, 10.1016/0006-8993(80)90780-5
- Hamann Scott R., Martin William R., Thermally evoked tail avoidance reflex: Input-output relationships and their modulation, 10.1016/0361-9230(92)90090-k
- Yarnitsky David, Ochoa Jose L., Studies of heat pain sensation in man: perception thresholds, rate of stimulus rise and reaction time : , 10.1016/0304-3959(90)91055-n
- YARNITSKY DAVID, OCHOA JOSE L., WARM AND COLD SPECIFIC SOMATOSENSORY SYSTEMS : PSYCHOPHYSICAL THRESHOLDS, REACTION TIMES AND PERIPHERAL CONDUCTION VELOCITIES, 10.1093/brain/114.4.1819
- Langford Lauren A., Coggeshall Richard E., Branching of sensory axons in the peripheral nerve of the rat, 10.1002/cne.902030411
- Tandrup T., Are the neurons in the dorsal root ganglion pseudounipolar? A comparison of the number of neurons and number of myelinated and unmyelinated fibres in the dorsal root, 10.1002/cne.903570302
- Waddell P.J., S.N. Lawson, McCarthy P.W., Conduction velocity changes along the processes of rat primary sensory neurons, 10.1016/0306-4522(89)90152-8
- McCarthy Peter W., Prabhakar Elizabeth, Lawson Sally N., Evidence to support the peripheral branching of primary afferent C-fibres in the rat: an in vitro intracellular electrophysiological study, 10.1016/0006-8993(95)01107-2
- D Le Bars, Pharmacol Rev, 53, 597 (2001)
- Ness T.J., Jones S.L., Gebhart G.F., Contribution of the site of heating to variability in the latency of the rat tail flick reflex, 10.1016/0006-8993(87)90437-9
- Martínez-Gómez Margarita, Cruz Yolanda, Salas Manuel, Hudson Robyn, Pacheco Pablo, Assessing pain threshold in the rat: Changes with estrus and time of day, 10.1016/0031-9384(94)90040-x
- Cesare P., McNaughton P., A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin, 10.1073/pnas.93.26.15435
- OG Berge, 77 (2002)
- Hole Kjell, Berge Odd-Geir, Tjølsen Arne, Eide Per K., Garcia-Cabrera Inmaculada, Lund Anders, Rosland Jan H., The tail-flick test needs to be improved : , 10.1016/0304-3959(90)90039-g
- &NA; &NA;, Ethical standards for investigations of experimental pain in animals : , 10.1016/0304-3959(80)90002-0
- Zimmermann Manfred, Ethical guidelines for investigations of experimental pain in conscious animals : , 10.1016/0304-3959(83)90201-4
- Grossman M. L., Basbaum A. I., Fields H. L., Afferent and efferent connections of the rat tail flick reflex (a model used to analyze pain control mechanisms), 10.1002/cne.902060103
- H Waibl, Adv Anat Embryol Cell Biol, 47, 1 (1973)
- Calvino B., Villanueva L., Le Bars D., The heterotopic effects of visceral pain: Behavioural and electrophysiological approaches in the rat : , 10.1016/0304-3959(84)90015-0
- Gordon Christopher J., Thermal biology of the laboratory rat, 10.1016/0031-9384(90)90025-y
- JD Hardy, J Appl Physiol, 9, 257 (1956)
- AM Stoll, J Appl Physiol, 14, 373 (1959)
- Tillman D B, Treede R D, Meyer R A, Campbell J N, Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: correlation with pain threshold in humans., 10.1113/jphysiol.1995.sp020767
- Meyer Richard A., Walker Ronald E., Mountcastle Vernon B., A Laser Stimulator for the Study of Cutaneous Thermal and Pain Sensations, 10.1109/tbme.1976.324616
- Bromm Burkhart, Treede Rolf-Detlef, CO2 laser radiant heat pulses activate C nociceptors in man, 10.1007/bf00663913
- Haimi-Cohen Raziel, Cohen Arnon, Carmon Amiram, A model for the temperature distribution in skin noxiously stimulated by a brief pulse of CO2 laser radiation, 10.1016/0165-0270(83)90113-9
- D Brown (1993)
- K Buettner, J Appl Physiol, 3, 691 (1951)
- Campbell James N., LaMotte Robert H., Latency to detection of first pain, 10.1016/0006-8993(83)90650-9
- B Bromm, Hum Neurobiol, 3, 33 (1984)
- HO Handwerker, Physiol Rev, 73, 639 (1993)
- Young A. A., Dawson N. J., Evidence for on–off control of heat dissipation from the tail of the rat, 10.1139/y82-057
Bibliographic reference |
Benoist, Jean-Michel ; Pincedé, Ivanne ; Ballantyne, Kay ; Plaghki, Léon ; Le Bars, Daniel. Peripheral and central determinants of a nociceptive reaction: an approach to psychophysics in the rat.. In: PloS one, Vol. 3, no. 9, p. e3125 (2008) |
Permanent URL |
http://hdl.handle.net/2078.1/28121 |