Skip to main content

The Pharmacology of Nociceptor Priming

  • Chapter
Pain Control

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 227))

Abstract

Nociceptors and neurons in the central nervous system (CNS) that receive nociceptive input show remarkable plasticity in response to injury. This plasticity is thought to underlie the development of chronic pain states. Hence, further understanding of the molecular mechanisms driving and maintaining this plasticity has the potential to lead to novel therapeutic approaches for the treatment of chronic pain states. An important concept in pain plasticity is the presence and persistence of “hyperalgesic priming.” This priming arises from an initial injury and results in a remarkable susceptibility to normally subthreshold noxious inputs causing a prolonged pain state in primed animals. Here we describe our current understanding of how this priming is manifested through changes in signaling in the primary nociceptor as well as through memory like alterations at CNS synapses. Moreover, we discuss how commonly utilized analgesics, such as opioids, enhance priming therefore potentially contributing to the development of persistent pain states. Finally we highlight where these priming models draw parallels to common human chronic pain conditions. Collectively, these advances in our understanding of pain plasticity reveal a variety of targets for therapeutic intervention with the potential to reverse rather than palliate chronic pain states.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abraham WC, Williams JM (2008) LTP maintenance and its protein synthesis-dependence. Neurobiol Learn Mem 89:260–268

    Article  CAS  PubMed  Google Scholar 

  • Aley KO, Levine JD (1999) Role of protein kinase A in the maintenance of inflammatory pain. J Neurosci 19:2181–2186

    CAS  PubMed  Google Scholar 

  • Aley KO, Messing RO, Mochly-Rosen D, Levine JD (2000) Chronic hypersensitivity for inflammatory nociceptor sensitization mediated by the epsilon isozyme of protein kinase C. J Neurosci 20:4680–4685

    CAS  PubMed  Google Scholar 

  • Althaus A, Hinrichs-Rocker A, Chapman R, Arranz Becker O, Lefering R, Simanski C, Weber F, Moser KH, Joppich R, Trojan S, Gutzeit N, Neugebauer E (2012) Development of a risk index for the prediction of chronic post-surgical pain. Eur J Pain 16:901–910

    Article  CAS  PubMed  Google Scholar 

  • Andersson GB (1999) Epidemiological features of chronic low-back pain. Lancet 354:581–585

    Article  CAS  PubMed  Google Scholar 

  • Asiedu MN, Tillu DV, Melemedjian OK, Shy A, Sanoja R, Bodell B, Ghosh S, Porreca F, Price TJ (2011) Spinal protein kinase M zeta underlies the maintenance mechanism of persistent nociceptive sensitization. J Neurosci 31:6646–6653

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Atkins CM, Davare MA, Oh MC, Derkach V, Soderling TR (2005) Bidirectional regulation of cytoplasmic polyadenylation element-binding protein phosphorylation by Ca2+/calmodulin-dependent protein kinase II and protein phosphatase 1 during hippocampal long-term potentiation. J Neurosci 25:5604–5610

    Article  CAS  PubMed  Google Scholar 

  • Balkowiec A, Katz DM (2000) Activity-dependent release of endogenous brain-derived neurotrophic factor from primary sensory neurons detected by ELISA in situ. J Neurosci 20:7417–7423

    CAS  PubMed  Google Scholar 

  • Bartleson JD (2001) Low back pain. Curr Treat Options Neurol 3:159–168

    Article  PubMed  Google Scholar 

  • Bassell GJ, Warren ST (2008) Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 60:201–214

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bigal ME, Lipton RB (2008) Clinical course in migraine: conceptualizing migraine transformation. Neurology 71:848–855

    Article  PubMed  Google Scholar 

  • Bogen O, Alessandri-Haber N, Chu C, Gear RW, Levine JD (2012) Generation of a pain memory in the primary afferent nociceptor triggered by PKCε activation of CPEB. J Neurosci 32:2018–2026

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cabanero D, Campillo A, Celerier E, Romero A, Puig MM (2009a) Pronociceptive effects of remifentanil in a mouse model of postsurgical pain: effect of a second surgery. Anesthesiology 111:1334–1345

    Article  CAS  PubMed  Google Scholar 

  • Cabanero D, Celerier E, Garcia-Nogales P, Mata M, Roques BP, Maldonado R, Puig MM (2009b) The pro-nociceptive effects of remifentanil or surgical injury in mice are associated with a decrease in delta-opioid receptor mRNA levels: prevention of the nociceptive response by on-site delivery of enkephalins. Pain 141:88–96

    Article  CAS  PubMed  Google Scholar 

  • Carey TS, Garrett JM, Jackman A, Hadler N (1999) Recurrence and care seeking after acute back pain: results of a long-term follow-up study. North Carolina Back Pain Project. Med Care 37:157–164

    Article  CAS  PubMed  Google Scholar 

  • Carling D, Thornton C, Woods A, Sanders MJ (2012) AMP-activated protein kinase: new regulation, new roles? Biochem J 445:11–27

    Article  CAS  PubMed  Google Scholar 

  • Cassidy JD, Cote P, Carroll LJ, Kristman V (2005) Incidence and course of low back pain episodes in the general population. Spine (Phila Pa 1976) 30:2817–2823

    Article  Google Scholar 

  • Cazorla M, Premont J, Mann A, Girard N, Kellendonk C, Rognan D (2011) Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice. J Clin Invest 121:1846–1857

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Celerier E, Rivat C, Jun Y, Laulin JP, Larcher A, Reynier P, Simonnet G (2000) Long-lasting hyperalgesia induced by fentanyl in rats: preventive effect of ketamine. Anesthesiology 92:465–472

    Article  CAS  PubMed  Google Scholar 

  • Celerier E, Laulin JP, Corcuff JB, Le Moal M, Simonnet G (2001) Progressive enhancement of delayed hyperalgesia induced by repeated heroin administration: a sensitization process. J Neurosci 21:4074–4080

    CAS  PubMed  Google Scholar 

  • Corder G, Doolen S, Donahue RR, Winter MK, Jutras BL, He Y, Hu X, Wieskopf JS, Mogil JS, Storm DR, Wang ZJ, McCarson KE, Taylor BK (2013) Constitutive mu-opioid receptor activity leads to long-term endogenous analgesia and dependence. Science 341:1394–1399

    Article  CAS  PubMed  Google Scholar 

  • Croft PR, Lewis M, Papageorgiou AC, Thomas E, Jayson MI, Macfarlane GJ, Silman AJ (2001) Risk factors for neck pain: a longitudinal study in the general population. Pain 93:317–325

    Article  CAS  PubMed  Google Scholar 

  • Dina OA, Khasar SG, Gear RW, Levine JD (2009) Activation of Gi induces mechanical hyperalgesia poststress or inflammation. Neuroscience 160:501–507

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Drdla R, Gassner M, Gingl E, Sandkuhler J (2009) Induction of synaptic long-term potentiation after opioid withdrawal. Science 325:207–210

    Article  CAS  PubMed  Google Scholar 

  • Drdla-Schutting R, Benrath J, Wunderbaldinger G, Sandkuhler J (2012) Erasure of a spinal memory trace of pain by a brief, high-dose opioid administration. Science 335:235–238

    Article  CAS  PubMed  Google Scholar 

  • Eijkelkamp N, Wang H, Garza-Carbajal A, Willemen HL, Zwartkruis FJ, Wood JN, Dantzer R, Kelley KW, Heijnen CJ, Kavelaars A (2010) Low nociceptor GRK2 prolongs prostaglandin E2 hyperalgesia via biased cAMP signaling to Epac/Rap1, protein kinase Cepsilon, and MEK/ERK. J Neurosci 30:12806–12815

    Article  CAS  PubMed  Google Scholar 

  • Ferrari LF, Bogen O, Alessandri-Haber N, Levine E, Gear RW, Levine JD (2012) Transient decrease in nociceptor GRK2 expression produces long-term enhancement in inflammatory pain. Neuroscience 222:392–403

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ferrari LF, Bogen O, Levine JD (2013a) Role of nociceptor alphaCaMKII in transition from acute to chronic pain (hyperalgesic priming) in male and female rats. J Neurosci 33:11002–11011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ferrari LF, Bogen O, Chu C, Levine JD (2013b) Peripheral administration of translation inhibitors reverses increased hyperalgesia in a model of chronic pain in the rat. J Pain 14:731–738

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gardell LR, Wang R, Burgess SE, Ossipov MH, Vanderah TW, Malan TP Jr, Lai J, Porreca F (2002) Sustained morphine exposure induces a spinal dynorphin-dependent enhancement of excitatory transmitter release from primary afferent fibers. J Neurosci 22:6747–6755

    CAS  PubMed  Google Scholar 

  • Gardell LR, King T, Ossipov MH, Rice KC, Lai J, Vanderah TW, Porreca F (2006) Opioid receptor-mediated hyperalgesia and antinociceptive tolerance induced by sustained opiate delivery. Neurosci Lett 396:44–49

    Article  CAS  PubMed  Google Scholar 

  • Garraway SM, Petruska JC, Mendell LM (2003) BDNF sensitizes the response of lamina II neurons to high threshold primary afferent inputs. Eur J Neurosci 18:2467–2476

    Article  PubMed  Google Scholar 

  • Harris W (1921) Persistent pain in lesions of the peripheral and central nervous system. Br Med J 2:896–900

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Herdy B et al (2012) Translational control of the activation of transcription factor NF-kappaB and production of type I interferon by phosphorylation of the translation factor eIF4E. Nat Immunol 13:543–550

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hucho TB, Dina OA, Levine JD (2005) Epac mediates a cAMP-to-PKC signaling in inflammatory pain: an isolectin B4(+) neuron-specific mechanism. J Neurosci 25:6119–6126

    Article  CAS  PubMed  Google Scholar 

  • Huganir RL, Nicoll RA (2013) AMPARs and synaptic plasticity: the last 25 years. Neuron 80:704–717

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Joseph EK, Levine JD (2010) Hyperalgesic priming is restricted to isolectin B4-positive nociceptors. Neuroscience 169:431–435

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Joseph EK, Parada CA, Levine JD (2003) Hyperalgesic priming in the rat demonstrates marked sexual dimorphism. Pain 105:143–150

    Article  CAS  PubMed  Google Scholar 

  • Joseph EK, Bogen O, Alessandri-Haber N, Levine JD (2007) PLC-beta 3 signals upstream of PKC epsilon in acute and chronic inflammatory hyperalgesia. Pain 132:67–73

    Article  CAS  PubMed  Google Scholar 

  • Joseph EK, Reichling DB, Levine JD (2010) Shared mechanisms for opioid tolerance and a transition to chronic pain. J Neurosci 30:4660–4666

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kerr BJ, Bradbury EJ, Bennett DL, Trivedi PM, Dassan P, French J, Shelton DB, McMahon SB, Thompson SW (1999) Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA-evoked responses in the rat spinal cord. J Neurosci 19:5138–5148

    CAS  PubMed  Google Scholar 

  • Khasar SG, Burkham J, Dina OA, Brown AS, Bogen O, Alessandri-Haber N, Green PG, Reichling DB, Levine JD (2008) Stress induces a switch of intracellular signaling in sensory neurons in a model of generalized pain. J Neurosci 28:5721–5730

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Klein T, Stahn S, Magerl W, Treede RD (2008) The role of heterosynaptic facilitation in long-term potentiation (LTP) of human pain sensation. Pain 139:507–519

    Article  PubMed  Google Scholar 

  • Kolb E, Canjuga M, Bauer GF, Laubli T (2011) Course of back pain across 5 years: a retrospective cohort study in the general population of Switzerland. Spine (Phila Pa 1976) 36:E268–E273

    Article  Google Scholar 

  • Laferriere A, Pitcher MH, Haldane A, Huang Y, Cornea V, Kumar N, Sacktor TC, Cervero F, Coderre TJ (2011) PKMzeta is essential for spinal plasticity underlying the maintenance of persistent pain. Mol Pain 7:99

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lee AM, Kanter BR, Wang D, Lim JP, Zou ME, Qiu C, McMahon T, Dadgar J, Fischbach-Weiss SC, Messing RO (2013) Prkcz null mice show normal learning and memory. Nature 493:416–419

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lipton RB (2009) Tracing transformation: chronic migraine classification, progression, and epidemiology. Neurology 72:S3–S7

    Article  PubMed  Google Scholar 

  • Lu Y, Christian K, Lu B (2008) BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem 89:312–323

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ma W, Ribeiro-da-Silva A, De Koninck Y, Radhakrishnan V, Cuello AC, Henry JL (1997) Substance P and enkephalin immunoreactivities in axonal boutons presynaptic to physiologically identified dorsal horn neurons. An ultrastructural multiple-labelling study in the cat. Neuroscience 77:793–811

    Article  CAS  PubMed  Google Scholar 

  • Macrae WA (2001) Chronic pain after surgery. Br J Anaesth 87:88–98

    Article  CAS  PubMed  Google Scholar 

  • Mannion RJ, Costigan M, Decosterd I, Amaya F, Ma QP, Holstege JC, Ji RR, Acheson A, Lindsay RM, Wilkinson GA, Woolf CJ (1999) Neurotrophins: peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity. Proc Natl Acad Sci U S A 96:9385–9390

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mao J, Price DD, Mayer DJ (1995) Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Pain 62:259–274

    Article  CAS  PubMed  Google Scholar 

  • Matayoshi S, Jiang N, Katafuchi T, Koga K, Furue H, Yasaka T, Nakatsuka T, Zhou XF, Kawasaki Y, Tanaka N, Yoshimura M (2005) Actions of brain-derived neurotrophic factor on spinal nociceptive transmission during inflammation in the rat. J Physiol 569:685–695

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Melemedjian OK, Asiedu MN, Tillu DV, Peebles KA, Yan J, Ertz N, Dussor GO, Price TJ (2010) IL-6- and NGF-induced rapid control of protein synthesis and nociceptive plasticity via convergent signaling to the eIF4F complex. J Neurosci 30:15113–15123

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Melemedjian OK, Asiedu MN, Tillu DV, Sanoja R, Yan J, Lark A, Khoutorsky A, Johnson J, Peebles KA, Lepow T, Sonenberg N, Dussor G, Price TJ (2011) Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain. Mol Pain 7:70

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Melemedjian OK, Tillu DV, Asiedu MN, Mandell EK, Moy JK, Blute VM, Taylor CJ, Ghosh S, Price TJ (2013a) BDNF regulates atypical PKC at spinal synapses to initiate and maintain a centralized chronic pain state. Mol Pain 9:12

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Melemedjian OK, Khoutorsky A, Sorge RE, Yan J, Asiedu MN, Valdez A, Ghosh S, Dussor G, Mogil JS, Sonenberg N, Price TJ (2013b) mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK. Pain 154(7):1080–1091

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Melemedjian OK, Mejia GL, Lepow TS, Zoph OK, Price TJ (2014) Bidirectional regulation of P body formation mediated by eIF4F complex formation in sensory neurons. Neurosci Lett 563:169–174

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mendez R, Hake LE, Andresson T, Littlepage LE, Ruderman JV, Richter JD (2000) Phosphorylation of CPE binding factor by Eg2 regulates translation of c-mos mRNA. Nature 404:302–307

    Article  CAS  PubMed  Google Scholar 

  • Migues PV, Hardt O, Wu DC, Gamache K, Sacktor TC, Wang YT, Nader K (2010) PKMzeta maintains memories by regulating GluR2-dependent AMPA receptor trafficking. Nat Neurosci 13:630–634

    Article  CAS  PubMed  Google Scholar 

  • Misra UK, Pizzo SV (2009) Epac1-induced cellular proliferation in prostate cancer cells is mediated by B-Raf/ERK and mTOR signaling cascades. J Cell Biochem 108:998–1011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nicoll RA, Roche KW (2013) Long-term potentiation: peeling the onion. Neuropharmacology 74:18–22

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nolet PS, Cote P, Cassidy JD, Carroll LJ (2010) The association between a lifetime history of a neck injury in a motor vehicle collision and future neck pain: a population-based cohort study. Eur Spine J 19:972–981

    Article  PubMed Central  PubMed  Google Scholar 

  • Parada CA, Yeh JJ, Reichling DB, Levine JD (2003) Transient attenuation of protein kinase Cepsilon can terminate a chronic hyperalgesic state in the rat. Neuroscience 120:219–226

    Article  CAS  PubMed  Google Scholar 

  • Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC (2006) Storage of spatial information by the maintenance mechanism of LTP. Science 313:1141–1144

    Article  CAS  PubMed  Google Scholar 

  • Pezet S, Malcangio M, Lever IJ, Perkinton MS, Thompson SW, Williams RJ, McMahon SB (2002) Noxious stimulation induces Trk receptor and downstream ERK phosphorylation in spinal dorsal horn. Mol Cell Neurosci 21:684–695

    Article  CAS  PubMed  Google Scholar 

  • Pinto PR, McIntyre T, Ferrero R, Almeida A, Araujo-Soares V (2013) Risk factors for moderate and severe persistent pain in patients undergoing total knee and hip arthroplasty: a prospective predictive study. PLoS One 8:e73917

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Price TJ, Dussor G (2013) AMPK: an emerging target for modification of injury-induced pain plasticity. Neurosci Lett 557(Pt A):9–18

    Article  CAS  PubMed  Google Scholar 

  • Price TJ, Ghosh S (2013) ZIPping to pain relief: the role (or not) of PKMzeta in chronic pain. Mol Pain 9:6

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Price TJ, Melemedjian OK (2012) Fragile X mental retardation protein (FMRP) and the spinal sensory system. Results Probl Cell Differ 54:41–59

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Price TJ, Rashid MH, Millecamps M, Sanoja R, Entrena JM, Cervero F (2007) Decreased nociceptive sensitization in mice lacking the fragile X mental retardation protein: role of mGluR1/5 and mTOR. J Neurosci 27:13958–13967

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Reichling DB, Levine JD (2009) Critical role of nociceptor plasticity in chronic pain. Trends Neurosci 32:611–618

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Reichling DB, Green PG, Levine JD (2013) The fundamental unit of pain is the cell. Pain 154(Suppl 1):S2–S9

    Article  PubMed  Google Scholar 

  • Ribeiro-da-Silva A, De Koninck Y, Cuello AC, Henry JL (1992) Enkephalin-immunoreactive nociceptive neurons in the cat spinal cord. Neuroreport 3:25–28

    Article  CAS  PubMed  Google Scholar 

  • Richter JD (2007) CPEB: a life in translation. Trends Biochem Sci 32:279–285

    Article  CAS  PubMed  Google Scholar 

  • Rivat C, Laulin JP, Corcuff JB, Celerier E, Pain L, Simonnet G (2002) Fentanyl enhancement of carrageenan-induced long-lasting hyperalgesia in rats: prevention by the N-methyl-D-aspartate receptor antagonist ketamine. Anesthesiology 96:381–391

    Article  CAS  PubMed  Google Scholar 

  • Rivat C, Laboureyras E, Laulin J-P, Le Roy C, Richebé P, Simonnet G (2007) Non-nociceptive environmental stress induces hyperalgesia, not analgesia, in pain and opioid-experienced rats. Neuropsychopharmacology 32:2217–2228

    Article  CAS  PubMed  Google Scholar 

  • Rivat C, Bollag L, Richebe P (2013) Mechanisms of regional anaesthesia protection against hyperalgesia and pain chronicization. Curr Opin Anaesthesiol 26(5):621–625

    Google Scholar 

  • Russe OQ, Moser CV, Kynast KL, King TS, Stephan H, Geisslinger G, Niederberger E (2013) Activation of the AMP-activated protein kinase reduces inflammatory nociception. J Pain 14:1330–1340

    Article  CAS  PubMed  Google Scholar 

  • Sacktor TC (2011) How does PKMzeta maintain long-term memory? Nat Rev Neurosci 12:9–15

    Article  CAS  PubMed  Google Scholar 

  • Sandkuhler J (2007) Understanding LTP in pain pathways. Mol Pain 3:9

    Article  PubMed Central  PubMed  Google Scholar 

  • Schroeder JE, McCleskey EW (1993) Inhibition of Ca2+ currents by a mu-opioid in a defined subset of rat sensory neurons. J Neurosci 13:867–873

    CAS  PubMed  Google Scholar 

  • Schroeder JE, Fischbach PS, Zheng D, McCleskey EW (1991) Activation of mu opioid receptors inhibits transient high- and low-threshold Ca2+ currents, but spares a sustained current. Neuron 6:13–20

    Article  CAS  PubMed  Google Scholar 

  • Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M, Cantley LC (2005) The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310:1642–1646

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shen CH, Yuan P, Perez-Lorenzo R, Zhang Y, Lee SX, Ou Y, Asara JM, Cantley LC, Zheng B (2013) Phosphorylation of BRAF by AMPK impairs BRAF-KSR1 association and cell proliferation. Mol Cell 52:161–172

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Si K, Lindquist S, Kandel ER (2003a) A neuronal isoform of the aplysia CPEB has prion-like properties. Cell 115:879–891

    Article  CAS  PubMed  Google Scholar 

  • Si K, Giustetto M, Etkin A, Hsu R, Janisiewicz AM, Miniaci MC, Kim JH, Zhu H, Kandel ER (2003b) A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia. Cell 115:893–904

    Article  CAS  PubMed  Google Scholar 

  • Sonenberg N, Hinnebusch AG (2009) Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136:731–745

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tamcan O, Mannion AF, Eisenring C, Horisberger B, Elfering A, Muller U (2010) The course of chronic and recurrent low back pain in the general population. Pain 150:451–457

    Article  PubMed  Google Scholar 

  • Tao YX (2012) AMPA receptor trafficking in inflammation-induced dorsal horn central sensitization. Neurosci Bull 28:111–120

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tillu DV, Melemedjian OK, Asiedu MN, Qu N, De Felice M, Dussor G, Price TJ (2012) Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain. Mol Pain 8:5

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Udagawa T, Swanger SA, Takeuchi K, Kim JH, Nalavadi V, Shin J, Lorenz LJ, Zukin RS, Bassell GJ, Richter JD (2012) Bidirectional control of mRNA translation and synaptic plasticity by the cytoplasmic polyadenylation complex. Mol Cell 47:253–266

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ueda T, Sasaki M, Elia AJ, Chio II, Hamada K, Fukunaga R, Mak TW (2010) Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development. Proc Natl Acad Sci U S A 107:13984–13990

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vanderah TW, Suenaga NM, Ossipov MH, Malan TP Jr, Lai J, Porreca F (2001) Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance. J Neurosci 21:279–286

    CAS  PubMed  Google Scholar 

  • Volk LJ, Bachman JL, Johnson R, Yu Y, Huganir RL (2013) PKM-zeta is not required for hippocampal synaptic plasticity, learning and memory. Nature 493:420–423

    Article  CAS  PubMed  Google Scholar 

  • Von Korff M, Saunders K (1996) The course of back pain in primary care. Spine (Phila Pa 1976) 21:2833–2837, discussion 2838–2839

    Article  Google Scholar 

  • Wang X, Flynn A, Waskiewicz AJ, Webb BL, Vries RG, Baines IA, Cooper JA, Proud CG (1998) The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways. J Biol Chem 273:9373–9377

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Heijnen CJ, van Velthoven CT, Willemen HL, Ishikawa Y, Zhang X, Sood AK, Vroon A, Eijkelkamp N, Kavelaars A (2013) Balancing GRK2 and EPAC1 levels prevents and relieves chronic pain. J Clin Invest 123(12):5023–5034

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wu C, Guo Y, Su Y, Zhang X, Luan H, Zhang X, Zhu H, He H, Wang X, Sun G, Sun X, Guo P, Zhu P (2014) Cordycepin activates AMP-activated protein kinase (AMPK) via interaction with the gamma1 subunit. J Cell Mol Med 18(2):293–304

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao J, Seereeram A, Nassar MA, Levato A, Pezet S, Hathaway G, Morenilla-Palao C, Stirling C, Fitzgerald M, McMahon SB, Rios M, Wood JN (2006) Nociceptor-derived brain-derived neurotrophic factor regulates acute and inflammatory but not neuropathic pain. Mol Cell Neurosci 31:539–548

    Article  CAS  PubMed  Google Scholar 

  • Zhou LJ, Zhong Y, Ren WJ, Li YY, Zhang T, Liu XG (2008) BDNF induces late-phase LTP of C-fiber evoked field potentials in rat spinal dorsal horn. Exp Neurol 212:507–514

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH grants NS065926 and GM102575 to T.J.P.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Theodore J. Price .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Kandasamy, R., Price, T.J. (2015). The Pharmacology of Nociceptor Priming. In: Schaible, HG. (eds) Pain Control. Handbook of Experimental Pharmacology, vol 227. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46450-2_2

Download citation

Publish with us

Policies and ethics