Abstract
To date, animal models have not sufficiently “filtered” targets for new analgesics, increasing the failure rate and cost of drug development. Preclinical assessment of “pain” has historically relied on measures of evoked behavioral responses to sensory stimuli in animals. Such measures can often be observed in decerebrated animals and therefore may not sufficiently capture affective and motivational aspects of pain, potentially diminishing translation from preclinical studies to the clinical setting. Further, evidence indicates that there are important mechanistic differences between evoked behavioral responses of hypersensitivity and ongoing pain, limiting evaluation of mechanisms that could mediate aspects of clinically relevant pain. The mechanisms underlying ongoing pain in preclinical models are currently being explored and may serve to inform decisions towards the transition from drug discovery to drug development for a given target.
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Ablin JN, Buskila D (2013) Personalized treatment of pain. Curr Rheumatol Rep 15:298
Andrews N, Legg E, Lisak D, Issop Y, Richardson D, Harper S, Pheby T, Huang W, Burgess G, Machin I, Rice AS (2012) Spontaneous burrowing behavior in the rat is reduced by peripheral nerve injury or inflammation associated pain. Eur J Pain 16:485–495
Attal N, Cruccu G, Haanpää M, Hansson P, Jensen TS, Nurmikko T, Sampaio C, Sindrup S, Wiffen P (2006) EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol 13:1153–1169
Backonja M, Woolf CJ (2010) Future directions in neuropathic pain therapy: closing the translational loop. Oncologist 15(Suppl 2):24–29
Ballantine HT Jr, Cassidy WL, Flanagan NB, Marino R Jr (1967) Stereotaxic anterior cingulotomy for neuropsychiatric illness and intractable pain. J Neurosurg 26:488–495
Baron R (2006) Mechanisms of disease: neuropathic pain–a clinical perspective. Nat Clin Pract Neurol 2:95–106
Basbaum AI, Bautista DM, Scherrer G, Julius D (2009) Cellular and molecular mechanisms of pain. Cell 139:267–284
Becerra L, Borsook D (2008) Signal valence in the nucleus accumbens to pain onset and offset. Eur J Pain 12:866–869
Borsook D, Erpelding N, Becerra L (2013) Losses and gains: chronic pain and altered brain morphology. Expert Rev Neurother 13:1221–1234
Borszcz GS (1993) The capacity of motor reflex and vocalization thresholds to support avoidance conditioning in the rat. Behav Neurosci 107:678–693
Borszcz GS (1995) Increases in vocalization and motor reflex thresholds are influenced by the site of morphine microinjection: comparisons following administration into the periaqueductal gray, ventral medulla, and spinal subarachnoid space. Behav Neurosci 109:502–522
Borszcz GS (2006) Contribution of the ventromedial hypothalamus to generation of the affective dimension of pain. Pain 123:155–168
Borszcz GS, Johnson CP, Fahey KA (1994) Comparison of motor reflex and vocalization thresholds following systemically administered morphine, fentanyl, and diazepam in the rat: assessment of sensory and performance variables. Pharmacol Biochem Behav 49:827–834
Bove SE, Flatters SJ, Inglis JJ, Mantyh PW (2009) New advances in musculoskeletal pain. Brain Res Rev 60:187–201
Campbell JN, Meyer RA (2006) Mechanisms of neuropathic pain. Neuron 52:77–92
Clauw DJ (2009) Fibromyalgia: an overview. Am J Med 122:S3–S13
Cleeland CS, Body JJ, Stopeck A, von Moos R, Fallowfield L, Mathias SD, Patrick DL, Clemons M, Tonkin K, Masuda N, Lipton A, de Boer R, Salvagni S, Oliveira CT, Qian Y, Jiang Q, Dansey R, Braun A, Chung K (2013) Pain outcomes in patients with advanced breast cancer and bone metastases: results from a randomized, double-blind study of denosumab and zoledronic acid. Cancer 119:832–838
Cobos EJ, Ghasemlou N, Araldi D, Segal D, Duong K, Woolf CJ (2012) Inflammation-induced decrease in voluntary wheel running in mice: a nonreflexive test for evaluating inflammatory pain and analgesia. Pain 153:876–884
Costigan M, Scholz J, Woolf CJ (2009) Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci 32:1–32
De Felice M, Eyde N, Dodick D, Dussor GO, Ossipov MH, Fields HL, Porreca F (2013) Capturing the aversive state of cephalic pain preclinically. Ann Neurol 74(2):257–265
De Felice M, Sanoja R, Wang R, Vera-Portocarrero L, Oyarzo J, King T, Ossipov MH, Vanderah TW, Lai J, Dussor GO, Fields HL, Price TJ, Porreca F (2011) Engagement of descending inhibition from the rostral ventromedial medulla protects against chronic neuropathic pain. Pain 152:2701–2709
Deacon RM (2006) Burrowing in rodents: a sensitive method for detecting behavioral dysfunction. Nat Protoc 1:118–121
Deacon RM (2009) Burrowing: a sensitive behavioral assay, tested in five species of laboratory rodents. Behav Brain Res 200:128–133
Deacon RM, Raley JM, Perry VH, Rawlins JN (2001) Burrowing into prion disease. NeuroReport 12:2053–2057
Devor M (1991) Sensory basis of autotomy in rats. Pain 45:109–110
Devor M (2009) Ectopic discharge in Abeta afferents as a source of neuropathic pain. Exp Brain Res 196:115–128
Djouhri L, Koutsikou S, Fang X, McMullan S, Lawson SN (2006) Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors. J Neurosci 26:1281–1292
Doods H, Arndt K, Rudolf K, Just S (2007) CGRP antagonists: unravelling the role of CGRP in migraine. Trends Pharmacol Sci 28:580–587
Dowdall T, Robinson I, Meert TF (2005) Comparison of five different rat models of peripheral nerve injury. Pharmacol Biochem Behav 80:93–108
Ducreux D, Attal N, Parker F, Bouhassira D (2006) Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study in syringomyelia. Brain: J Neurol 129:963–976
Dworkin RH, O’Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ, Portenoy RK, Rice ASC, Stacey BR, Treede R-D, Turk DC, Wallace MS (2007) Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 132:237–251
Eisenach JC, Hood DD, Curry R (2000) Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia. Pain 84:57–64
Eisenach JC, Rauck RL, Curry R (2003) Intrathecal, but not intravenous adenosine reduces allodynia in patients with neuropathic pain. Pain 105:65–70
Farrell KE, Keely S, Graham BA, Callister R, Callister RJ (2014) A systematic review of the evidence for central nervous system plasticity in animal models of inflammatory-mediated gastrointestinal pain. Inflamm Bowel Dis 20:176–195
Fields HL (1999) Pain: an unpleasant topic. Pain Suppl 6:S61–S69
Finan PH, Smith MT (2013) The comorbidity of insomnia, chronic pain, and depression: dopamine as a putative mechanism. Sleep Med Rev 17:173–183
Foltz EL, White LE Jr (1962) Pain “relief” by frontal cingulumotomy. J Neurosurg 19:89–100
Freeman KT, Koewler NJ, Jimenez-Andrade JM, Buus RJ, Herrera MB, Martin CD, Ghilardi JR, Kuskowski MA, Mantyh PW (2008) A fracture pain model in the rat: adaptation of a closed femur fracture model to study skeletal pain. Anesthesiology 108:473–483
Fuchs PN, McNabb CT (2012) The place escape/avoidance paradigm: a novel method to assess nociceptive processing. J Integr Neurosci 11:61–72
Goesling J, Clauw DJ, Hassett AL (2013) Pain and depression: an integrative review of neurobiological and psychological factors. Curr Psychiatry Rep 15:421
Goldenberg DL (2009) Diagnosis and differential diagnosis of fibromyalgia. Am J Med 122:S14–S21
Guenther K, Deacon RMJ, Perry VH, Rawlins JN (2001) Early behavioural changes in scrapie-affected mice and the influence of dapsone. Eur J Neurosci 14:401–409
Halvorson KG, Kubota K, Sevcik MA, Lindsay TH, Sotillo JE, Ghilardi JR, Rosol TJ, Boustany L, Shelton DL, Mantyh PW (2005) A blocking antibody to nerve growth factor attenuates skeletal pain induced by prostate tumor cells growing in bone. Cancer Res 65:9426–9435
Harte SE, Kender RG, Borszcz GS (2005) Activation of 5-HT1A and 5-HT7 receptors in the parafascicular nucleus suppresses the affective reaction of rats to noxious stimulation. Pain 113:405–415
Harte SE, Spuz CA, Borszcz GS (2011) Functional interaction between medial thalamus and rostral anterior cingulate cortex in the suppression of pain affect. Neuroscience 172:460–473
Hawker GA, Stewart L, French MR, Cibere J, Jordan JM, March L, Suarez-Almazor M, Gooberman-Hill R (2008) Understanding the pain experience in hip and knee osteoarthritis—an OARSI/OMERACT initiative. Osteoarthr Cartil 16:415–422
Hofbauer RK, Rainville P, Duncan GH, Bushnell MC (2001) Cortical representation of the sensory dimension of pain. J Neurophysiol 86:402–411
Honore P, Chandran P, Hernandez G, Gauvin DM, Mikusa JP, Zhong C, Joshi SK, Ghilardi JR, Sevcik MA, Fryer RM, Segreti JA, Banfor PN, Marsh K, Neelands T, Bayburt E, Daanen JF, Gomtsyan A, Lee CH, Kort ME, Reilly RM, Surowy CS, Kym PR, Mantyh PW, Sullivan JP, Jarvis MF, Faltynek CR (2009) Repeated dosing of ABT-102, a potent and selective TRPV1 antagonist, enhances TRPV1-mediated analgesic activity in rodents, but attenuates antagonist-induced hyperthermia. Pain 142:27–35
Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB, O’Keefe PF, Ramnaraine ML, Clohisy DR, Mantyh PW (2000) Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med 6:521–528
Huang W, Calvo M, Karu K, Olausen HR, Bathgate G, Okuse K, Bennett DL, Rice AS (2013) A clinically relevant rodent model of the HIV antiretroviral drug stavudine induced painful peripheral neuropathy. Pain 154:560–575
Hummel M, Lu P, Cummons TA, Whiteside GT (2008) The persistence of a long-term negative affective state following the induction of either acute or chronic pain. Pain 140:436–445
Hurt RW, Ballantine HT Jr (1974) Stereotactic anterior cingulate lesions for persistent pain: a report on 68 cases. Clin Neurosurg 21:334–351
Johansen JP, Fields HL (2004) Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal. Nat Neurosci 7:398–403
Johansen JP, Fields HL, Manning BH (2001) The affective component of pain in rodents: direct evidence for a contribution of the anterior cingulate cortex. Proc Natl Acad Sci USA 98:8077–8082
Kehlet H, Jensen TS, Woolf CJ (2006) Persistent postsurgical pain: risk factors and prevention. Lancet 367:1618–1625
Kender RG, Harte SE, Munn EM, Borszcz GS (2008) Affective analgesia following muscarinic activation of the ventral tegmental area in rats. J Pain: Off J Am Pain Soc 9:597–605
Kesslak JP, Keirstead HS (2003) Assessment of behavior in animal models of spinal cord injury. J Spinal Cord Med 26:323–328
King T, Qu C, Okun A, Mercado R, Ren J, Brion T, Lai J, Porreca F (2011) Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity. Pain 152(9):1997–2005
King T, Vera-Portocarrero L, Gutierrez T, Vanderah TW, Dussor G, Lai J, Fields HL, Porreca F (2009) Unmasking the tonic-aversive state in neuropathic pain. Nat Neurosci 12:1364–1366
Koewler NJ, Freeman KT, Buus RJ, Herrera MB, Jimenez-Andrade JM, Ghilardi JR, Peters CM, Sullivan LJ, Kuskowski MA, Lewis JL, Mantyh PW (2007) Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6 J mouse femur. J Bone Miner Res: Off J Am Soc Bone Miner Res 22:1732–1742
LaBuda CJ, Fuchs PN (2001) Low dose aspirin attenuates escape/avoidance behavior, but does not reduce mechanical hyperalgesia in a rodent model of inflammatory pain. Neurosci Lett 304:137–140
LaGraize SC, Borzan J, Peng YB, Fuchs PN (2006) Selective regulation of pain affect following activation of the opioid anterior cingulate cortex system. Exp Neurol 197:22–30
LaGraize SC, Labuda CJ, Rutledge MA, Jackson RL, Fuchs PN (2004) Differential effect of anterior cingulate cortex lesion on mechanical hypersensitivity and escape/avoidance behavior in an animal model of neuropathic pain. Exp Neurol 188:139–148
Langford DJ, Bailey AL, Chanda ML, Clarke SE, Drummond TE, Echols S, Glick S, Ingrao J, Klassen-Ross T, Lacroix-Fralish ML, Matsumiya L, Sorge RE, Sotocinal SG, Tabaka JM, Wong D, van den Maagdenberg AM, Ferrari MD, Craig KD, Mogil JS (2010) Coding of facial expressions of pain in the laboratory mouse. Nat Methods 7:447–449
Lau W, Dykstra C, Thevarkunnel S, Silenieks LB, de Lannoy IA, Lee DK, Higgins GA (2013) A back translation of pregabalin and carbamazepine against evoked and non-evoked endpoints in the rat spared nerve injury model of neuropathic pain. Neuropharmacology 73:204–215
Lipton A, Balakumaran A (2012) Denosumab for the treatment of cancer therapy-induced bone loss and prevention of skeletal-related events in patients with solid tumors. Expert Rev Clin Pharmacol 5:359–371
Liu P, Okun A, Ren J, Guo RC, Ossipov MH, Xie J, King T, Porreca F (2011) Ongoing pain in the MIA model of osteoarthritis. Neurosci Lett 493:72–75
Luger NM, Honore P, Sabino MA, Schwei MJ, Rogers SD, Mach DB, Clohisy DR, Mantyh PW (2001) Osteoprotegerin diminishes advanced bone cancer pain. Cancer Res 61:4038–4047
Maier C, Baron R, Tolle TR, Binder A, Birbaumer N, Birklein F, Gierthmuhlen J, Flor H, Geber C, Huge V, Krumova EK, Landwehrmeyer GB, Magerl W, Maihofner C, Richter H, Rolke R, Scherens A, Schwarz A, Sommer C, Tronnier V, Uceyler N, Valet M, Wasner G, Treede RD (2010) Quantitative sensory testing in the German research network on neuropathic pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain 150:439–450
Mantyh PW (2014a) Bone cancer pain: from mechanism to therapy. Current Opin Support Palliat Care 8:83–90
Mantyh PW (2014b) The neurobiology of skeletal pain. Eur J Neurosci 39:508–519
Mao J (2012) Current challenges in translational pain research. Trends Pharmacol Sci 33:568–573
Martin TJ, Kim SA, Buechler NL, Porreca F, Eisenach JC (2007) Opioid self-administration in the nerve-injured rat: relevance of antiallodynic effects to drug consumption and effects of intrathecal analgesics. Anesthesiology 106:312–322
Martin TJ, Kim SA, Eisenach JC (2006) Clonidine maintains intrathecal self-administration in rats following spinal nerve ligation. Pain 125:257–263
Matsumiya LC, Sorge RE, Sotocinal SG, Tabaka JM, Wieskopf JS, Zaloum A, King OD, Mogil JS (2012) Using the mouse grimace scale to reevaluate the efficacy of postoperative analgesics in laboratory mice. J Am Assoc Lab Anim Sci 51:42–49
Melzack R, Casey K (1968) Sensory, motivational, and central control determinants of pain. In: Kenshalo DR (ed) The skin senses. Charles C. Thomas, Springfield, pp 423–443
Meng ID, Dodick D, Ossipov MH, Porreca F (2011) Pathophysiology of medication overuse headache: insights and hypotheses from preclinical studies. Cephalalgia: Int J Headache 31:851–860
Mercadante S, Porzio G, Gebbia V (2012) Spinal analgesia for advanced cancer patients: an update. Crit Rev Oncol Hematol 82:227–232
Mogil JS (2009) Animal models of pain: progress and challenges. Nat Rev Neurosci 10:283–294
Mogil JS, Lichtensteiger CA, Wilson SG (1998) The effect of genotype on sensitivity to inflammatory nociception: characterization of resistant (A/J) and sensitive (C57BL/6 J) inbred mouse strains. Pain 76:115–125
Mogil JS, Richards SP, O’Toole LA, Helms ML, Mitchell SR, Belknap JK (1997) Genetic sensitivity to hot-plate nociception in DBA/2 J and C57BL/6 J inbred mouse strains: possible sex-specific mediation by delta2-opioid receptors. Pain 70:267–277
Mogil JS, Wilson SG, Bon K, Lee SE, Chung K, Raber P, Pieper JO, Hain HS, Belknap JK, Hubert L, Elmer GI, Chung JM, Devor M (1999a) Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception. Pain 80:67–82
Mogil JS, Wilson SG, Bon K, Lee SE, Chung K, Raber P, Pieper JO, Hain HS, Belknap JK, Hubert L, Elmer GI, Chung JM, Devor M (1999b) Heritability of nociception II. ‘Types’ of nociception revealed by genetic correlation analysis. Pain 80:83–93
Moisset X, Bouhassira D (2007) Brain imaging of neuropathic pain. Neuroimage 37(Suppl 1):S80–S88
Nandigama P, Borszcz GS (2003) Affective analgesia following the administration of morphine into the amygdala of rats. Brain Res 959:343–354
Navratilova E, Xie JY, Okun A, Qu C, Eyde N, Ci S, Ossipov MH, King T, Fields HL, Porreca F (2012) Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry. Proc Natl Acad Sci USA 109:20709–20713
Okun A, DeFelice M, Eyde N, Ren J, Mercado R, King T, Porreca F (2011) Transient inflammation-induced ongoing pain is driven by TRPV1 sensitive afferents. Mol Pain 7:4
Okun A, Liu P, Davis P, Ren J, Remeniuk B, Brion T, Ossipov MH, Xie J, Dussor GO, King T, Porreca F (2012) Afferent drive elicits ongoing pain in a model of advanced osteoarthritis. Pain 153:924–933
Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U, Pollentier S, Lesko LM, Group BBCPoCS (2004) Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 350:1104–1110
Percie du Sert N, Rice AS (2014) Improving the translation of analgesic drugs to the clinic: animal models of neuropathic pain. Brit J Pharmacol 171(12):2951–2963
Peroutka SJ (2014) Calcitonin gene-related peptide targeted immunotherapy for migraine: progress and challenges in treating headache. BioDrugs: Clin Immunother Biopharm Gene Ther 28:237–244
Petrovic P, Kalso E, Petersson KM, Ingvar M (2002) Placebo and opioid analgesia—imaging a shared neuronal network. Science 295:1737–1740
Peyron R, Faillenot I, Pomares FB, Le Bars D, Garcia-Larrea L, Laurent B (2013) Mechanical allodynia in neuropathic pain. Where are the brain representations located? A positron emission tomography (PET) study. Eur J Pain 17:1327–1337
Peyron R, Garcia-Larrea L, Gregoire MC, Convers P, Lavenne F, Veyre L, Froment JC, Mauguiere F, Michel D, Laurent B (1998) Allodynia after lateral-medullary (Wallenberg) infarct. A PET study. Brain: J Neurol 121(Pt 2):345–356
Pfau DB, Krumova EK, Treede RD, Baron R, Toelle T, Birklein F, Eich W, Geber C, Gerhardt A, Weiss T, Magerl W, Maier C (2014) Quantitative sensory testing in the German research network on neuropathic pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia. Pain 155(5):1002–1015
Pope JE, Deer TR (2013) Ziconotide: a clinical update and pharmacologic review. Expert Opin Pharmacother 14:957–966
Puttfarcken PS, Han P, Joshi SK, Neelands TR, Gauvin DM, Baker SJ, Lewis LG, Bianchi BR, Mikusa JP, Koenig JR, Perner RJ, Kort ME, Honore P, Faltynek CR, Kym PR, Reilly RM (2010) A-995662 [(R)-8-(4-methyl-5-(4-(trifluoromethyl)phenyl)oxazol-2-ylamino)-1,2,3,4-tetrahydr onaphthalen-2-ol], a novel, selective TRPV1 receptor antagonist, reduces spinal release of glutamate and CGRP in a rat knee joint pain model. Pain 150:319–326
Qu C, King T, Okun A, Lai J, Fields HL, Porreca F (2011) Lesion of the rostral anterior cingulate cortex eliminates the aversiveness of spontaneous neuropathic pain following partial or complete axotomy Pain (in press)
Rainville P (2002) Brain mechanisms of pain affect and pain modulation. Curr Opin Neurobiol 12:195–204
Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC (1997) Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 277:968–971
Rainville P, Hofbauer RK, Bushnell MC, Duncan GH, Price DD (2002) Hypnosis modulates activity in brain structures involved in the regulation of consciousness. J Cogn Neurosci 14:887–901
Rainville P, Hofbauer RK, Paus T, Duncan GH, Bushnell MC, Price DD (1999) Cerebral mechanisms of hypnotic induction and suggestion. J Cogn Neurosci 11:110–125
Rodin BE, Kruger L (1984) Deafferentation in animals as a model for the study of pain: an alternative hypothesis. Brain Res 319:213–228
Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, Binder A, Birbaumer N, Birklein F, Botefur IC, Braune S, Flor H, Huge V, Klug R, Landwehrmeyer GB, Magerl W, Maihofner C, Rolko C, Schaub C, Scherens A, Sprenger T, Valet M, Wasserka B (2006) Quantitative sensory testing in the German research network on neuropathic pain (DFNS): standardized protocol and reference values. Pain 123:231–243
Rosenzweig ES, McDonald JW (2004) Rodent models for treatment of spinal cord injury: research trends and progress toward useful repair. Curr Opin Neurol 17:121–131
Rutten K, Robens A, Read SJ, Christoph T (2013a) Pharmacological validation of a refined burrowing paradigm for prediction of analgesic efficacy in a rat model of sub-chronic knee joint inflammation. European J Pain 18:213–222
Rutten K, Schiene K, Robens A, Leipelt A, Pasqualon T, Read SJ, Christoph T (2013b) Burrowing as a non-reflex behavioral readout for analgesic action in a rat model of sub-chronic knee joint inflammation. Eur J Pain 8(2):204–212
Sarzi-Puttini P, Vellucci R, Zuccaro SM, Cherubino P, Labianca R, Fornasari D (2012) The appropriate treatment of chronic pain. Clin Drug Invest 32:21–33
Schaible H-G, Ebersberger A, Natura G (2011) Update on peripheral mechanisms of pain: beyond prostaglandins and cytokines. Arthritis Res Ther 13:210
Schott E, Berge OG, Angeby-Moller K, Hammarstrom G, Dalsgaard CJ, Brodin E (1994) Weight bearing as an objective measure of arthritic pain in the rat. J Pharmacol Toxicol Methods 31:79–83
Schwei MJ, Honore P, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML, Clohisy DR, Mantyh PW (1999) Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. J Neurosci 19:10886–10897
Seidel MF, Wise BL, Lane NE (2013) Nerve growth factor: an update on the science and therapy. Osteoarthr Cartil 21:1223–1228
Sevcik MA, Ghilardi JR, Peters CM, Lindsay TH, Halvorson KG, Jonas BM, Kubota K, Kuskowski MA, Boustany L, Shelton DL, Mantyh PW (2005) Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain 115:128–141
Sotocinal SG, Sorge RE, Zaloum A, Tuttle AH, Martin LJ, Wieskopf JS, Mapplebeck JC, Wei P, Zhan S, Zhang S, McDougall JJ, King OD, Mogil JS (2011) The rat grimace scale: a partially automated method for quantifying pain in the laboratory rat via facial expressions. Mol Pain 7:55
Spuz CA, Borszcz GS (2012) NMDA or non-NMDA receptor antagonism within the amygdaloid central nucleus suppresses the affective dimension of pain in rats: evidence for hemispheric synergy. J Pain: Off J Am Pain Soc 13:328–337
Stevenson GW, Mercer H, Cormier J, Dunbar C, Benoit L, Adams C, Jezierski J, Luginbuhl A, Bilsky EJ (2011) Monosodium iodoacetate-induced osteoarthritis produces pain-depressed wheel running in rats: implications for preclinical behavioral assessment of chronic pain. Pharmacol Biochem Behav 98:35–42
Sufka KJ (1994) Conditioned place preference paradigm: a novel approach for analgesic drug assessment against chronic pain. Pain 58:355–366
Ugolini G, Marinelli S, Covaceuszach S, Cattaneo A, Pavone F (2007) The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain. Proc Natl Acad Sci USA 104:2985–2990
Uhelski ML, Morris-Bobzean SA, Dennis TS, Perrotti LI, Fuchs PN (2012) Evaluating underlying neuronal activity associated with escape/avoidance behavior in response to noxious stimulation in adult rats. Brain Res 1433:56–61
Vera-Portocarrero LP, Lu Y, Westlund KN (2003) Nociception in persistent pancreatitis in rats: effects of morphine and neuropeptide alterations. Anesthesiology 98:474–484
Vierck CJ, Hansson PT, Yezierski RP (2008) Clinical and pre-clinical pain assessment: are we measuring the same thing? Pain 135:7–10
von Hehn CA, Baron R, Woolf CJ (2012) Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron 73:638–652
Vrinten DH, Hamers FF (2003) ‘CatWalk’ automated quantitative gait analysis as a novel method to assess mechanical allodynia in the rat; a comparison with von Frey testing. Pain 102:203–209
Wermeling DP, Berger JR (2006) Ziconotide infusion for severe chronic pain: case series of patients with neuropathic pain. Pharmacother: J Hum Pharmacol Drug Ther 26:395–402
Whittle SL, Colebatch AN, Buchbinder R, Edwards CJ, Adams K, Englbrecht M, Hazlewood G, Marks JL, Radner H, Ramiro S, Richards BL, Tarner IH, Aletaha D, Bombardier C, Landewé RB, Müller-Ladner U, Bijlsma JWJ, Branco JC, Bykerk VP, da Rocha Castelar Pinheiro G, Catrina AI, Hannonen P, Kiely P, Leeb B, Lie E, Martinez-Osuna P, Montecucco C, Østergaard M, Westhovens R, Zochling J, van der Heijde D (2012) Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis: integrating systematic literature research and expert opinion of a broad panel of rheumatologists in the 3e Initiative. Rheumatology 51:1416–1425
Wild KD, Bian D, Zhu D, Davis J, Bannon AW, Zhang TJ, Louis JC (2007) Antibodies to nerve growth factor reverse established tactile allodynia in rodent models of neuropathic pain without tolerance. J Pharmacol Exp Ther 322:282–287
Witting N, Kupers RC, Svensson P, Jensen TS (2006) A PET activation study of brush-evoked allodynia in patients with nerve injury pain. Pain 120:145–154
Woolf CJ (1984) Long term alterations in the excitability of the flexion reflex produced by peripheral tissue injury in the chronic decerebrate rat. Pain 18:325–343
Woolf CJ (2007) Central sensitization: uncovering the relation between pain and plasticity. Anesthesiology 106:864–867
Woolf CJ (2011) Central sensitization: implications for the diagnosis and treatment of pain. Pain 152:S2–S15
Xu J, Brennan TJ (2009) Comparison of skin incision vs. skin plus deep tissue incision on ongoing pain and spontaneous activity in dorsal horn neurons. Pain 144:329–339
Xu J, Brennan TJ (2010) Guarding pain and spontaneous activity of nociceptors after skin versus skin plus deep tissue incision. Anesthesiology 112:153–164
Xu Q, Yaksh TL (2011) A brief comparison of the pathophysiology of inflammatory versus neuropathic pain. Curr Opin Anaesthesiol 24:400–407
Xu XJ, Puke MJ, Wiesenfeld-Hallin Z (1992) The depressive effect of intrathecal clonidine on the spinal flexor reflex is enhanced after sciatic nerve section in rats. Pain 51:145–151
Yoon YW, Lee DH, Lee BH, Chung K, Chung JM (1999) Different strains and substrains of rats show different levels of neuropathic pain behaviors. Exp Brain Res 129:167–171
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King, T., Porreca, F. (2014). Preclinical Assessment of Pain: Improving Models in Discovery Research. In: Taylor, B., Finn, D. (eds) Behavioral Neurobiology of Chronic Pain. Current Topics in Behavioral Neurosciences, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2014_330
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