我要登录|
免费注册
|
我的丁香通
- 企业机构：
- 成为企业机构
- 个人用户：
- 个人中心
移动端

大家都在搜

0 人通过求购买到了急需的产品

免费发布求购

发布求购

Behavioral Measures of Pain Thresholds

互联网2013-12-31

1622

Abstract
Table of Contents
Materials
Figures
Literature Cited

Abstract

Pain afflicts a fifth of the population, and animal models have proven useful in target validation and analgesic drug development. Thresholds to pain are tested by applying a sensory stimulus, such as heat or pressure, and observing the resulting withdrawal behavior. Sensitized pain models involve provoking an inflammatory response or damaging the nerves themselves, and testing the changes in pain threshold. In this article, mouse models of acute mechanical and thermal pain and inflammatory, visceral, and neuropathic pain are discussed. These behavioral measures can be used to phenotype transgenic mice for target validation and mechanistic studies, as well as to screen potential analgesic compounds. Curr. Protoc. Mouse Biol. 1:383?412 © 2011 by John Wiley & Sons, Inc.

Keywords: nociception; reflex; pain; neuropathic; inflammatory; visceral

GO TO THE FULL PROTOCOL:

PDF or HTML at Wiley Online Library

Introduction
Strategic Planning
Testing Thresholds to Thermal Stimuli
Basic Protocol 1: Radiant Heat Tail‐Flick
Alternate Protocol 1: Hot Water Immersion Tail‐Flick
Alternate Protocol 2: Cold Water Immersion Tail‐Flick
Basic Protocol 2: Hot Plate: Nociceptive Response to Noxious Heat
Basic Protocol 3: Cold Plate: Noxious Cold
Basic Protocol 4: Hargreaves' Test: Withdrawal Threshold to Noxious Heat
Support Protocol 1: Alternative Measurement for Hargreaves' Apparatus
Basic Protocol 5: Acetone Evaporation Test: Innocuous Cooling and Cold Allodynia
Testing Thresholds to Mechanical Stimuli
Basic Protocol 6: Von Frey Test: Light Touch Perception Threshold
Support Protocol 2: Repeated Measures Von Frey Test
Alternate Protocol 3: Automatic Von Frey Test
Basic Protocol 7: Randall‐Selitto Test: Noxious Mechanical Pressure
Alternate Protocol 4: Digital Paw Pressure Test
Inflammatory Pain
Basic Protocol 8: Mechanical and/or Thermal Hyperalgesia in the Hindpaw
Alternate Protocol 5: Spontaneous Inflammatory Pain
Visceral Pain
Basic Protocol 9: Intracolonic Administration of Irritants
Support Protocol 3: Von Frey Hair
Neuropathic Pain: Hyperalgesic Allodynia Mediated by Peripheral Nerve Damage
Basic Protocol 10: Chronic Constriction Injury (CCI): Loose Ligation of the Sciatic Nerve
Alternate Protocol 6: Seltzer: Partial Ligation of the Sciatic Nerve
Alternate Protocol 7: Spinal Nerve Ligation (SNL)
Commentary
Literature Cited
Figures
Tables

GO TO THE FULL PROTOCOL:

PDF or HTML at Wiley Online Library

Materials

Basic Protocol 1: Radiant Heat Tail‐Flick

Materials

Mice of optimal age (6 to 8 weeks)
Mouse restrainer (consisting of base plate, body tube, and head cover)
Infrared heat source with built‐in timer and motion detector. (e.g., Tail Flick Analgesia Meter #33; IITC Life Science, http://www.iitcinc.com/)
Infrared heat‐flux radiometer (Ugo Basile, cat. no. 37300), for calibrating and maintaining apparatus

Alternate Protocol 1: Hot Water Immersion Tail‐Flick

Mice of optimal age (6 to 8 weeks)
Water bath
Thermometer (accurate to 0.5°C)
Timer

Alternate Protocol 2: Cold Water Immersion Tail‐Flick

Materials

Mice of optimal age (6 to 8 weeks)
Hot plate apparatus with enclosure (e.g., Hot/Cold Plate; Ugo Basile, cat. no. 35100)
Surface thermometer, for calibrating and maintaining apparatus (optional)

Basic Protocol 2: Hot Plate: Nociceptive Response to Noxious Heat

Materials

Mice of optimal age (6 to 8 weeks)
Cold plate apparatus with enclosure (e.g. Hot/Cold Plate; Ugo Basile, cat. no. 35100)
Surface thermometer, for calibrating and maintaining apparatus (optional)

Basic Protocol 3: Cold Plate: Noxious Cold

Materials

Mice of optimal age (6 to 8 weeks)
Hargreaves' apparatus, infrared or light (IITC Life Science, cat. no. 390; http://www.iitcinc.com/; Ugo Basile, cat. no. 37370)
Raised glass pane with clear plastic enclosures
Optional: Infrared heat‐flux radiometer (Ugo Basile, cat. no. 37300), for calibrating and maintaining apparatus

Basic Protocol 4: Hargreaves' Test: Withdrawal Threshold to Noxious Heat

Materials

Mice of optimal age (6 to 8 weeks)
Acetone

Test compartments with a mesh floor (e.g., Mesh Stand; IITC Life Science, cat. no. 410; http://www.iitcinc.com)
Acetone applicator (blunting two 33‐G needles and inserting them in either end of a 10‐cm length of thin tubing, and using a 5‐ml syringe, have approved successful previously; Fig. )
Two timers

Support Protocol 1: Alternative Measurement for Hargreaves' Apparatus

Materials

Mice of optimal age (6 to 8 weeks)
Test compartments with a mesh floor (e.g., Mesh Stand; IITC Life Science, cat. no. 410; http://www.iitcinc.com)
Calibrated set of von Frey hairs (e.g., Stoelting Touch Test Sensory Evaluator)

Basic Protocol 5: Acetone Evaporation Test: Innocuous Cooling and Cold Allodynia

Materials

Mice of optimal age (6 to 8 weeks)
Test compartments with a mesh floor (e.g., Mesh Stand; IITC Life Science, cat. no. 410; http://www.iitcinc.com)
Automatic von Frey apparatus (e.g., Electronic von Frey IITC Life Science, cat. no. 2390; http://www.iitcinc.com/)

Additional reagents and equipment for habituation of mice to von Frey apparatus ( protocol 9 )

Basic Protocol 6: Von Frey Test: Light Touch Perception Threshold

Materials

Mice of optimal age (6 to 8 weeks)
Mouse restrainer (consisting of base plate, body tube, and head cover)
Randall‐Selitto apparatus (e.g., Analgesy‐Meter; Ugo Basile, cat. no. 37215)

Support Protocol 2: Repeated Measures Von Frey Test

Materials

Mice of optimal age (6 to 8 weeks)
Mouse restrainer
Digital Paw Pressure Analgesia Instrument (IITC Life Science, cat. no. 2500)

Alternate Protocol 3: Automatic Von Frey Test

Materials

Mice of optimal age (6 to 8 weeks)
Hamilton syringe and 29‐G needle, or 0.5‐ml disposable insulin syringe
Inflammatory agent (see Table 11.1.1600 for concentrations and dosage)

Additional reagent and equipment for determining mechanical and thermal pain thresholds (see protocols above)

Basic Protocol 7: Randall‐Selitto Test: Noxious Mechanical Pressure

Materials

Mice of optimal age (6 to 8 weeks)
Inflammatory agent (see Table 11.1.1600 for concentrations and dosage)

Clear, lidded Perspex box, ∼15 cm × 15 cm
Mirror
Stopwatches
Hamilton syringe and 29‐G needle or 0.5‐ml disposable insulin syringe

Alternate Protocol 4: Digital Paw Pressure Test

Materials

Mice of optimal age (6 to 8 weeks)
Anesthetic (e.g., isoflurane)
Isoflurane
Oxygen
Irritant (mustard oil or capsaicin)

Catheter (0.6 mm diameter, ∼4 cm long; e.g., Harvard Apparatus, cat. no. 732851)
1‐ml syringe
Test compartment with mesh floor (e.g., IITC Life Science, cat. no. 410; http://www.iitcinc.com/)

Basic Protocol 8: Mechanical and/or Thermal Hyperalgesia in the Hindpaw

Calibrated set of von Frey hairs (e.g., Stoelting Touch Test Sensory Evaluator)

Alternate Protocol 5: Spontaneous Inflammatory Pain

Materials

Mice of optimal age (6 to 8 weeks)
Isoflurane
Oxygen
Iodine antiseptic solution

Apparatus for administering isoflurane anesthesia, including muzzle for mouse
Heat mat
Surgical swabs
Two size‐5 forceps
Size‐15 scalpel
3‐0 non‐absorbable suture
Suture needles and needle holders
3‐0 absorbable suture
Wound clips
Wound clip remover

Basic Protocol 9: Intracolonic Administration of Irritants

Dissection microscope

Support Protocol 3: Von Frey Hair

Surgical swabs
Retractor, glass hook: surgical hooks are commercially available; however these has proven awkward to use and can result in damage to the other sciatic nerve roots—using a Bunsen burner to melt and draw out glass Pasteur pipets into fine hooks has proven a more useful tool (Fig. )
Dissection microscope
Size‐7 forceps
Size‐11 scalpel
Micro‐scissors

GO TO THE FULL PROTOCOL:

PDF or HTML at Wiley Online Library

Figures

Figure 1. Mouse in a restrainer.

View Image
Figure 2. Acetone applicator.

View Image

Figure 3. Mouse paw. Circle indicates the area of the plantar surface of the paw to be stimulated (e.g., with von Frey hair), as well as the site for intraplantar injection. Scale bar = 1 mm.

View Image

Figure 4. CCI and Seltzer diagram.

View Image
Figure 5. SNL diagram.

View Image
Figure 6. Glass hook for surgery. Scale bar = 1 mm.

View Image

Videos

Literature Cited

Literature Cited
	Abrahamsen, B., Zhao, J., Asante, C.O., Cendan, C.M., Marsh, S., Martinez‐Barbera, J.P., Nassar, M.A., Dickenson, A.H., and Wood, J.N. 2008. The cell and molecular basis of mechanical, cold, and inflammatory pain. Science 321:702‐705.
	Baertschi, B. and Gyger, M. 2011. Ethical considerations in mouse experiments. Curr. Protoc. Mouse Biol. 1:155‐167.
	Ben‐Bassat, J., Peretz, E., and Sulman, F.G. 1959. Analgesimetry and ranking of analgesic drugs by the receptacle method. Arch. Int. Pharmacodyn. Ther. 122:434‐447.
	Bennett, G.J. 1994. Neuopathic Pain. pp 201‐224. Churchill Livingstone, London.
	Bennett, G.J. and Xie, Y.K. 1988. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33:87‐107.
	Callahan, B.L., Gil, A.S.C., Levesque, A., and Mogil, J.S. 2008. Modulation of mechanical and thermal nociceptive sensitivity in the laboratory mouse by behavioral state. J. Pain 9:174‐184.
	Chaplan, S.R., Bach, F.W., Pogrel, J.W., Chung, J.M., and Yaksh, T.L. 1994. Quantitative assessment of tactile allodynia in the rat paw. J. Neurosci. Methods 53:55‐63.
	Chapman, C.R., Casey, K.L., Dubner, R., Foley, K.M., Gracely, R.H., and Reading, A.E. 1985. Pain measurement: An overview. Pain 22:1‐31.
	Chesler, E.J., Wilson, S.G., Lariviere, W.R., Rodriguez‐Zas, S.L., and Mogil, J.S. 2002. Influences of laboratory environment on behavior. Nat. Neurosci. 5:1101‐1102.
	Chuang, H., Prescott, E.D., Kong, H., Shields, S., Jordt, S.E., Basbaum, A.I., Chao, M.V., and Julius, D. 2001. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2‐mediated inhibition. Nature 411:957‐962.
	Coderre, T.J., Vaccarino, A.L., and Melzack, R. 1990. Central nervous system plasticity in the tonic pain response to subcutaneous formalin injection. Brain Res. 535:155‐158.
	Couture, R., Harrisson, M., Vianna, R.M., Cloutier, F. 2001. Kinin receptors in pain and inflammation. Eur. J. Pharmacol. 429:161‐176.
	Crunkhorn, P. and Meacock, S.C. 1971. Mediators of the inflammation induced in the rat paw by carrageenin. Br. J. Pharmacol. 42:392‐402.
	Cunha, F.Q., Poole, S., Lorenzetti, B.B., and Ferreira, S.H. 1992. The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br. J. Pharmacol. 107:660‐664.
	D'Amour, F.E. and Smith, D.L. 1941. A method for determining loss of pain sensation. J. Pharmacol. Exp. Ther. 72:74‐79.
	Dixon, W.J. 1980. Efficient analysis of experimental observations. Annu. Rev. Pharmacol. Toxicol. 20:441‐462.
	Eddy, N.B. and Leimbach, D. 1953. Synthetic analgesics. II. Dithienylbutenyl‐ and dithienylbutylamines. J. Pharmacol. Exp. Ther. 107:385‐393.
	Gray, J.A . 1978. The neuropsychology of anxiety. Br. J. Psychol. 69:417‐434.
	Hargreaves, K., Dubner, R., Brown, F., Flores, C., and Joris, J. 1988. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77‐88.
	Kim, S.H. and Chung, J.M. 1992. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50:355‐363.
	Laird, J.M.A., Martinez‐Caro, L., Garcia‐Nicas, E., and Cervero, F. 2001. A new model of visceral pain and referred hyperalgesia in the mouse. Pain 92:335‐342.
	Larson, A.A., Brown, D.R., el‐Atrash, S., and Walser, M.M. 1986. Pain threshold changes in adjuvant‐induced inflammation: A possible model of chronic pain in the mouse. Pharmacol. Biochem. Behav. 24:49‐53.
	Lee, D.E., Kim, S.J., and Zhuo, M. 1999. Comparison of behavioral responses to noxious cold and heat in mice. Brain Res. 845:117‐121.
	Macdonald, A.D., Woolfe, G., Bergel, F., Morrison, A.L., and Rinderknecht, H. 1946. Analgesic action of pethidine derivatives and related compounds. Br. J. Pharmacol. Chemother. 1:4‐14.
	McNamara, C.R., Mandel‐Brehm, J., Bautista, D.M., Siemens, J., Deranian, K.L., Zhao, M., Hayward, N.J., Chong, J.A., Julius, D., Moran, M.M., and Fanger, C.M. 2007. TRPA1 mediates formalin‐induced pain. Proc. Natl. Acad. Sci. U.S.A. 104:13525‐13530.
	Meller, S.T. and Gebhart, G.F. 1997. Intraplantar zymosan as a reliable, quantifiable model of thermal and mechanical hyperalgesia in the rat. Eur. J. Pain 1:43‐52.
	Mogil, J.S., Wilson, S.G., Bon, K., Lee, S.E., Chung, K., Raber, P., Pieper, J.O., Hain, H.S., Belknap, J.K., Hubert, L., Elmer, G.I., Chung, J.M., and Devor, M . 1999. Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception. Pain 80:67‐82.
	Mogil, J., Wilson, S., and Wan, Y. 2001. Assessing nociception in murine subjects. In Methods in Pain Research ( L. Kruger, ed.) pp. 11‐40. CRC Press, Boca Raton, Fla.
	Pizziketti, R.J., Pressman, N.S., Geller, E.B., Cowan, A., and Adler, M.W. 1985. Rat cold water tail‐flick: A novel analgesic test that distinguishes opioid agonists from mixed agonist‐antagonists. Eur. J. Pharmacol. 119:23‐29.
	Rácz, I. and Zimmer, A. 2006. Animal Models of Nociception. Wiley‐VCH Verlag GmbH, Weinheim, Germany.
	Randall, L.O. and Selitto, J.J. 1957. A method for measurement of analgesic activity on inflamed tissue. Arch. Int. Pharmacodyn. Ther. 111:409‐419.
	Rosland, J.H., Tjlsen, A., Mühle, B.R., and Hole, K. 1990. The formalin test in mice: Effect of formalin concentration. Pain 42:235‐242.
	Seltzer, Z., Dubner, R., and Shir, Y. 1990. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 43:205‐218.
	Slugg, R.M., Meyer, R.A., and Campbell, J.N. 2000. Response of cutaneous A‐ and C‐fiber nociceptors in the monkey to controlled‐force stimuli. J. Neurophysiol. 83:2179‐2191.
	Southall, M.D. and Vasko, M.R. 2000. Prostaglandin E(2)‐mediated sensitization of rat sensory neurons is not altered by nerve growth factor. Neurosci. Lett. 287:33‐36.
	Taiwo, Y.O., Goetzl, E.J., and Levine, J.D. 1987. Hyperalgesia onset latency suggests a hierarchy of action. Brain Res. 423:333‐337.
	Takesue, E.I., Schaefer, W., and Jukniewicz, E. 1969. Modification of the Randall‐Selitto analgesic apparatus. J. Pharm. Pharmacol. 21:788‐789.
	Vetulani, J., Castellano, C., Lasón, W., and Oliverio, A. 1988. The difference in the tail‐flick but not hot‐plate response latency between C57BL/6 and DBA/2J mice. Pol. J. Pharmacol. Pharm. 40:381‐385.
	Wang, S., Dai, Y., Fukuoka, T., Yamanaka, H., Kobayashi, K., Obata, K., Cui, X., Tominaga, M., and Noguchi, K. 2008. Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: A molecular mechanism of inflammatory pain. Brain 131:1241‐1251.
	Zimmermann, K., Leffler, A., Babes, A., Cendan, C.M., Carr, R.W., Kobayashi, J., Nau, C., Wood, J.N., and Reeh, P.W. 2007. Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures. Nature 447:855‐858.