Involvement of Peripheral Purinoceptors in Sympathetic Modulation of Capsaicin-Induced Sensitization of Primary Afferent Fibers

Abstract

Ren, Yong, Xiaoju Zou, Li Fang, and Qing Lin. Involvement of peripheral purinoceptors in sympathetic modulation of capsaicin-induced sensitization of primary afferent fibers. J Neurophysiol 96: 2207-2216, 2006. First published August 2, 2006 doi:10.1152/jn.00502.2006. Purinoceptors are distributed in primary afferent terminals, where transmission of nociceptive information is modulated by these receptors. In the present study, we evaluated whether the activation or blockade of purinoceptors of subtypes P2X and P2Y in the periphery affected the sensitization of primary afferents induced by intradermal injection of capsaicin (CAP) and examined their role in sympathetic modulation of sensitization of primary nociceptive afferents. Afferent activity was recorded from single A␦-and C-primary afferent fibers in the tibial nerve in anesthetized rats. Peripheral pretreatment with ␣,␤-methylene adenosine 5Ј-triphosphate (␣,␤-meATP), a P2X-selective receptor agonist, could potentiate the CAP-induced enhancement of responses of A␦-and C-primary afferent nociceptive fibers to mechanical stimuli in sympathetically intact rats. After sympathetic denervation, the enhanced responses of both A␦-and C-fibers after CAP injection were dramatically reduced. However, this reduction could be restored when P2X receptors were activated by ␣,␤-meATP. A blockade of P2X receptors by pyridoxalphosphate-6-azophenyl-2Ј,4Ј-disulfonic acid could significantly reduce the CAP-induced sensitization of A␦-and C-fibers. Pretreatment with uridine 5Ј-triphosphate, a P2Y-selective receptor agonist, did not significantly affect or restore the CAP-induced sensitization of A␦-and C-fibers under sympathetically intact or sympathectomized conditions. Our study supports the view that ATP plays a role in modulation of primary afferent nociceptor sensitivity mainly by P2X receptors. Combined with our previous study, our data also provide further evidence that the sensitization of primary afferent nociceptors is subject to sympathetic modulation by activation of P2X as well as ␣ 1 -adrenergic receptors.

Octreotide inhibits capsaicin-induced activation of C and Aδ afferent fibres in rat hairy skin in vivo

“…Stimulation of the capsaicin-sensitive sensory nerve terminal evokes arteriolar vasodilatation and venular plasma protein extravasation in the innervated areas, 34,35 resulting in what is called neurogenic inflammation. 29,31,36 TRPV1 receptors are located on the small-diameter neurons of DRG with unmyelinated (C) and small myelinated (Ad) primary afferent nociceptive axons and confer sensitivity to capsaicin, noxious heat and acid. [17][18][19][37][38][39] Therefore, neurogenic inflammation is presumed to be initiated by activation of TRPV1 receptors, which subsequently indirectly triggers a mechanism that sensitizes the primary afferent to noxious stimuli.…”

The effects of sympathetic outflow on upregulation of vanilloid receptors TRPV1 in primary afferent neurons evoked by intradermal capsaicin

“…Since our previous studies have demonstrated that CAP-evoked inflammation and pain are sympathetically dependent (Lin et al, 2003,2004; Ren et al, 2005,2006), we wanted to evaluate further how inflammation was modulated sympathetically by released ATP, and the role of PKC in this process. Tests were done under sympathectomized conditions to examine the possibility that release of ATP from sympathetic efferent terminals participates in CAP-evoked inflammation by activating peripheral P2X or P2Y receptors.…”

“…solution (5 μg in 5 μl) was placed on the surface of each DRG for 10 min before CAP injection. Doses chosen for P2X and P2Y receptor agonists and PKC activator and inhibitor have been demonstrated to be selective for the target receptors and PKC, respectively, in other studies (Lin et al, 1996; Ren et al,2006; Xu et al, 2009; Zou et al, 2004). All drugs were freshly prepared on the day when the experiment was performed.…”

“…Many studies reveal that neurogenic inflammation and the resulting pain induced by intradermal injection of capsaicin (CAP) are sympathetically dependent (Coderre et al, 1989; Lin et al, 2003,2004; Ren et al, 2005,2006). Activation of transient receptor potential vanilloid-1 (TRPV 1 ) receptors in primary afferent nociceptive neurons and their axons evoked by CAP injection produces an efferent function that initiates neurogenic inflammation (Kessler et al, 1999; Szolcsanyi, 1996,2004) by the release of neuropeptides from the nociceptors (Garcia-Nicas et al, 2001; Li et al, 2008; Lin et al, 2007).…”

“…Activation of transient receptor potential vanilloid-1 (TRPV 1 ) receptors in primary afferent nociceptive neurons and their axons evoked by CAP injection produces an efferent function that initiates neurogenic inflammation (Kessler et al, 1999; Szolcsanyi, 1996,2004) by the release of neuropeptides from the nociceptors (Garcia-Nicas et al, 2001; Li et al, 2008; Lin et al, 2007). We proposed in our previous studies that neurogenic inflammation is likely to be sympathetically-mediated by influencing the sensitivity of primary afferent nociceptive neurons and/or their terminals (Ren et al, 2005,2006). However, no direct evidence has so far been provided to show if this process is done by modulation of TRPV 1 receptors.…”