The Pharmacology of Nociceptor Priming

  • Ram Kandasamy
  • Theodore J. PriceEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 227)


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.


Atypical PKC AMPA NMDA mTORC1 PKC Epac Hyperalgesic priming Prostaglandins NGF Interleukin 6 



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


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© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of PharmacologyThe University of ArizonaTucsonUSA
  2. 2.Bio5 InstituteThe University of ArizonaTucsonUSA
  3. 3.Graduate Interdisciplinary Program in NeuroscienceThe University of ArizonaTucsonUSA
  4. 4.School of Brain and Behavioral Sciences, The University of Texas at DallasRichardsonUSA

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