Experimental Brain Research

, Volume 196, Issue 1, pp 45–52

Regulation of firing frequency in nociceptive neurons by pro-inflammatory mediators


DOI: 10.1007/s00221-009-1744-2

Cite this article as:
Momin, A. & McNaughton, P.A. Exp Brain Res (2009) 196: 45. doi:10.1007/s00221-009-1744-2


Nociceptive neurons generate trains of action potentials in response to painful stimuli, and the frequency of firing signals the intensity of the pain. Pro-inflammatory mediators such as prostaglandin E2 (PGE2) enhance the sensation of pain by increasing the frequency of action potential firing in response to a given level of painful stimulus. The mechanism by which the firing frequency is enhanced is discussed in the present review. One hypothesis proposes that the threshold for action potential initiation is lowered because the activation curve of a nociceptor-specific voltage-activated Na current, NaV1.8, is shifted to more negative values by PGE2. Recent measurements in our lab show, however, that the action potential threshold in fact changes little when AP firing is accelerated by PGE2. The enhanced firing is, however, abolished by a blocker of an inward current activated by hyperpolarisation, called Ih. The voltage sensitivity of Ih shifts in the positive direction in small nociceptive neurons when they are exposed to pro-inflammatory mediators, such as PGE2, which activate adenylate cyclase and therefore increase levels of cAMP. By this mechanism the inward current between the resting membrane potential and the threshold for firing of action potentials is enhanced, and the rate of depolarisation in the interval between action potentials is therefore increased. We conclude that the major mechanism responsible for increasing action potential firing following tissue damage or metabolic stress is the hyperpolarisation-activated inward current, Ih, and that other mechanisms play at most a minor role.


Pain Sensory transduction Action potential Prostaglandin 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of CambridgeCambridgeUK

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