Chronic nerve growth factor administration increases the peripheral exocytotic a

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Neurosci Lett. 2006 Jun 13

Chronic nerve growth factor administration increases the peripheral

exocytotic activity of capsaicin-sensitive cutaneous neurons.

Bowles WR, Sabino M, Harding-Rose C, Hargreaves KM.

Division of Endodontics, University of Minnesota School of Dentistry,

8-166 Moos Tower, 515 Delaware St SE, Minneapolis, MN 55455, United

States.

Nerve growth factor (NGF) plays an important role in inflammation and

pain and has been suggested to regulate the responsiveness and

sensitivity of nociceptive fibers. However, no study has evaluated

whether chronic NGF alters the exocytotic capacity of peripheral

terminals of peptidergic fibers.

To test this hypothesis, rats were injected subcutaneously every

other day with either murine recombinant NGF (mNGF; 1.0mg/kg) or

vehicle for 7 days; or mNGF (0.1mg/kg), mNGF (1mg/kg) or vehicle

every other day for 13 days. Treatment of rats with NGF over a 13-day

period produced a significant increase in capsaicin-evoked iCGRP

release from isolated biopsies of hindpaw skin, as assessed by in

vitro superfusion and RIA.

This effect was dose-dependent and exhibited a temporal requirement,

because the enhancement was only observed after 13 days of treatment

and was not evident after 7 days of treatment. This NGF enhancement

of capsaicin-evoked iCGRP release was not due solely to increases in

peripheral iCGRP content since only the 1mg/kg dose of NGF elevated

cutaneous pools of iCGRP, whereas both doses significantly increased

capsaicin-evoked peptide release.

Moreover, NGF also enhanced capsaicin-evoked thermal hyperalgesia

under similar dose- and time-related conditions. Collectively, the

chronic administration of NGF not only increases capsaicin-evoked

hyperalgesia, but also significantly primes peripheral fibers to

enhanced peptidergic exocytosis following activation of the capsaicin

receptor.

Collectively, these data are consistent with the hypothesis that

persistently elevated NGF levels may contribute to enhanced

neurogenic regulation of inflammatory and wound healing processes in

injured tissue.