Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin

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Item Type:	Article
Title:	Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin
Creators Name:	Hamilton, S.G., McMahon, S.B. and Lewin, G.R.
Abstract:	1. ATP can elicit pain in humans and, together with other P2X channel agonists, can produce nocifensive responses in rodents. We used the rat in vitro skin-nerve preparation to quantify primary afferent responses to ATP and its stable analogue {alpha},{beta}-methylene ATP in normal and carrageenan-inflamed skin. 2. Both ATP and {alpha},{beta}-methylene ATP were found to specifically activate the peripheral terminals of A{delta} and C-fibre nociceptors in the skin. Thirty-nine per cent of the nociceptors tested responded to the maximal dose of {alpha},{beta}-methylene ATP (5 mM). In contrast, non-nociceptive, low-threshold mechano-sensitive fibres were never activated by the same agonist concentrations. 3. Amongst the nociceptor population, C-mechanoheat fibres (C-MH or polymodal nociceptors) were markedly more responsive to P2X agonists than mechanonociceptors (C-M nociceptors) with A{delta}- or C-fibre axons. Both C-mechanoheat and C-mechanonociceptors were activated by {alpha},{beta}-methylene ATP doses as low as 50 {my}M. 4. In skin inflamed with carrageenan 3-4 h before recording both the number of responsive C-fibre nociceptors and their response magnitude increased. The increased neural response under inflammatory conditions was largely observed in C-mechanoheat or polymodal nociceptors. After low doses of P2X agonists C-MH fibres but not C-M fibres developed elevated ongoing activity and this effect was only seen after carrageenan inflammation. The time course of {alpha},{beta}-methylene ATP-evoked discharges in nociceptors was found to correlate well with the time course of behavioural nocifensive responses in rats to the same agonist described in a previous study (Hamilton et al. 1999). 5. We conclude that the rapid increase in the number of {alpha},{beta}-methylene ATP responsive nociceptors and the increased magnitude of the neural response following carrageenan inflammation explains why very low concentrations of such agonists can cause pain in inflammatory states.
Keywords:	Adenosine Triphosphate, Carrageenan, Dermatitis, Drug Dose-Response Relationship, Nociceptors, Pain, Wistar Rats, Purinergic P2 Receptors, Skin, Animals, Rats
Source:	Journal of Physiology
ISSN:	0022-3751
Publisher:	Cambridge University Press
Volume:	534
Number:	2
Page Range:	437-445
Date:	1 January 2001
Official Publication:	https://doi.org/10.1111/j.1469-7793.2001.00437.x
PubMed:	View item in PubMed

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