Sympathetic Modulation of Acute Cutaneous Flare Induced by Intradermal Injection of Capsaicin in Anesthetized Rats

2003 ◽  
Vol 89 (2) ◽  
pp. 853-861 ◽  
Author(s):  
Qing Lin ◽  
Xiaoju Zou ◽  
Li Fang ◽  
William D. Willis
Keyword(s):  
Neurogenic Inflammation ◽  
Intradermal Injection ◽  
Primary Afferent ◽  
Laser Doppler Flow ◽  
Plantar Surface ◽  
Adrenoceptor Agonist ◽  
Injection Model ◽  
Sympathetic Modulation ◽  
Sympathetic Efferents ◽  
Afferent Terminals

Much of the acute cutaneous neurogenic inflammation after intradermal injection of capsaicin (CAP) in rats is mediated by dorsal root reflexes (DRRs), which cause the release of inflammatory agents from primary afferent terminals. Sympathetic efferents modulate neurogenic inflammation by interaction with primary afferent terminals. In this study, we examined if DRR-mediated flare after CAP injection is subject to sympathetic modulation. Changes in cutaneous blood flow on the plantar surface of the foot were measured using a laser Doppler flow meter. After CAP injection, cutaneous flare spread more than 20 mm away from the site of CAP injection. However, this CAP-induced flare was significantly reduced after surgical sympathectomy. Decentralization of postganglionic neurons did not affect the flare induced by CAP injection. If the foot of sympathectomized rats was pretreated with an α1-adrenoceptor agonist (phenylephrine) by intra-arterial injection, the spread of flare induced by CAP injection could be restored. However, if the spinal cord was pretreated with a GABAA receptor antagonist, bicuculline, to prevent DRRs, phenylephrine no longer restored the CAP-evoked flare. An α2-adrenoceptor agonist (UK14,304) did not affect the CAP-evoked flare in sympathectomized rats. In sympathetically intact rats, blockade of peripheral α1-adrenoceptors with terazosin profoundly reduced the flare induced by CAP injection, whereas blockade of peripheral α2-adrenoceptors by yohimbine did not obviously affect the flare. Therefore the pathogenesis of acute neurogenic inflammation in the intradermal CAP injection model depends in part on intact sympathetic efferents and α1-adrenoceptors. Peripheral α1-adrenoceptors thus modulate the ability of capsaicin sensitive afferents to evoke the release of inflammatory agents from primary afferents by DRRs.

Sympathetic Influence on Capsaicin-Evoked Enhancement of Dorsal Root Reflexes in Rats

2004 ◽  
Vol 92 (4) ◽  
pp. 2017-2026 ◽  
Author(s):  
Jing Wang ◽  
Yong Ren ◽  
Xiaoju Zou ◽  
Li Fang ◽  
William D. Willis ◽  
...  
Keyword(s):  
Dorsal Root ◽  
Neurogenic Inflammation ◽  
Intradermal Injection ◽  
Primary Afferent ◽  
Adrenoceptor Antagonist ◽  
Afferent Fibers ◽  
Adrenoceptor Agonist ◽  
Sympathetic Modulation ◽  
Sympathetic Influence ◽  
Series Of Experiments

A series of experiments by our group suggest that the initiation and development of neurogenic inflammation in rats are mainly mediated by dorsal root reflexes (DRRs), which are conducted centrifugally from the spinal dorsal horn in primary afferent nocieptors. In this study, DRRs were recorded in anesthetized rats from single afferent fibers in the proximal ends of cut dorsal root filaments at the L4–L6 level and tested for responses to intradermal injection of capsaicin. Sympathectomy combined with pharmacological manipulations were employed to determine if the capsaicin-evoked enhancement of DRRs was subject to sympathetic modulation. DRRs could be recorded from both myelinated (Aβ and Aδ) and unmyelinated (C) afferent fibers. After capsaicin was injected intradermally into the plantar foot, a significant enhancement of DRRs was seen in C- and Aδ-fibers but not in Aβ-fibers. This enhancement of DRRs evoked by capsaicin injection was almost completely prevented by sympathectomy. However, if peripheral α1-adrenoceptors were activated by intra-arterial injection of phenylephrine, the enhancement of DRRs evoked by capsaicin could be restored, whereas no such restoration was seen following pretreatment with an α2-adrenoceptor agonist, UK14,304. Under sympathetically intact conditions, the enhanced DRRs following capsaicin injection could be blocked by administration of terazosin, an α1-adrenoceptor antagonist, but not by administration of yohimbine, an α2-adrenoceptor antagonist. These results provide further evidence that the DRR-mediated neurogenic inflammation depends in part on intact sympathetic efferents acting on peripheral α1-adrenoceptors, which augment the sensitization of primary afferent nociceptors induced by capsaicin injection, helping trigger DRRs that produce vasodilation.

Sympathetic Modulation of Activity in Aδ- and C-Primary Nociceptive Afferents After Intradermal Injection of Capsaicin in Rats

2005 ◽  
Vol 93 (1) ◽  
pp. 365-377 ◽  
Author(s):  
Yong Ren ◽  
Xiaoju Zou ◽  
Li Fang ◽  
Qing Lin
Keyword(s):  
Adrenergic Receptors ◽  
Intradermal Injection ◽  
Mechanical Stimuli ◽  
Primary Afferent ◽  
C Fibers ◽  
Afferent Fibers ◽  
Sympathetic Modulation ◽  
Primary Afferent Fibers ◽  
Sympathetic Efferents ◽  
Intact Rats

Neuropathic and inflammatory pain can be modulated by the sympathetic nervous system. In some pain models, sympathetic postganglionic efferents are involved in the modulation of nociceptive transmission in the periphery. The purpose of this study is to examine the sensitization of Aδ- and C-primary afferent nociceptors induced by intradermal injection of capsaicin (CAP) to see whether the presence of sympathetic efferents is essential for the sensitization. Single primary afferent discharges were recorded from the tibial nerve after the fiber types were identified by conduction velocity in anesthetized rats. An enhanced response of some Aδ- and most C-primary afferent fibers to mechanical stimuli was seen in sham-sympathectomized rats after CAP (1%, 15 μl) injection, but the enhanced responses of both Aδ- and C-fibers were reduced after sympathetic postganglionic efferents were removed. Peripheral pretreatment with norepinephrine by intraarterial injection could restore and prolong the CAP-induced enhancement of responses under sympathectomized conditions. In sympathetically intact rats, pretreatment with an α1-adrenergic receptor antagonist (terazosin) blocked completely the enhanced responses of C-fibers after CAP injection in sympathetically intact rats without significantly affecting the enhanced responses of Aδ-fibers. In contrast, a blockade of α2-adrenergic receptors by yohimbine only slightly reduced the CAP-evoked enhancement of responses. We conclude that the presence of sympathetic efferents is essential for the CAP-induced sensitization of Aδ- and C-primary afferent fibers to mechanical stimuli and that α1-adrenergic receptors play a major role in the sympathetic modulation of C-nociceptor sensitivity in the periphery.

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

2006 ◽  
Vol 96 (5) ◽  
pp. 2207-2216 ◽  
Author(s):  
Yong Ren ◽  
Xiaoju Zou ◽  
Li Fang ◽  
Qing Lin
Keyword(s):  
Receptor Agonist ◽  
P2x Receptors ◽  
Intradermal Injection ◽  
Disulfonic Acid ◽  
Mechanical Stimuli ◽  
Primary Afferent ◽  
C Fibers ◽  
Afferent Fibers ◽  
Sympathetic Modulation ◽  
Primary Afferent Fibers

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 Aδ- and C-primary afferent fibers in the tibial nerve in anesthetized rats. Peripheral pretreatment with α,β-methylene adenosine 5′-triphosphate (α,β-meATP), a P2X-selective receptor agonist, could potentiate the CAP-induced enhancement of responses of Aδ- and C-primary afferent nociceptive fibers to mechanical stimuli in sympathetically intact rats. After sympathetic denervation, the enhanced responses of both Aδ- and C-fibers after CAP injection were dramatically reduced. However, this reduction could be restored when P2X receptors were activated by α,β-meATP. A blockade of P2X receptors by pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid could significantly reduce the CAP-induced sensitization of Aδ- and C-fibers. Pretreatment with uridine 5′-triphosphate, a P2Y-selective receptor agonist, did not significantly affect or restore the CAP-induced sensitization of Aδ- 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 α1-adrenergic receptors.

Role of the Na+-K+-2Cl− Cotransporter in the Development of Capsaicin-Induced Neurogenic Inflammation

2006 ◽  
Vol 95 (6) ◽  
pp. 3553-3561 ◽  
Author(s):  
Sandra Valencia-de Ita ◽  
Nada B. Lawand ◽  
Qing Lin ◽  
Gilberto Castañeda-Hernandez ◽  
William D. Willis
Keyword(s):  
Blood Flow ◽  
Mechanical Allodynia ◽  
Neurogenic Inflammation ◽  
Intradermal Injection ◽  
Plasma Extravasation ◽  
Sprague Dawley ◽  
Doppler Flowmetry ◽  
Plantar Surface ◽  
Sprague Dawley Rats ◽  
Electrophysiological Studies

Recent behavioral and electrophysiological studies have attributed an important role to dorsal root reflexes (DRRs) in the initiation and development of neurogenic inflammation produced by intradermal capsaicin (CAP). The DRRs can occur in peptidergic fibers, resulting in peripheral release of neuromediators that produce vasodilation, plasma extravasation and subsequently hyperalgesia and allodynia. In this study, we have evaluated the effect of spinal administration of bumetanide (a blocker of the Na+K+2Cl− cotransporter, NKCC) on DRR activity, changes in cutaneous blood flow (vasodilation), hindpaw edema, mechanical allodynia, and hyperalgesia induced by intradermal injection of 1% CAP in Sprague-Dawley rats. Vasodilation was monitored using laser Doppler flowmetry, neurogenic edema was evaluated by measurements of hindpaw volume, and secondary mechanical allodynia and hyperalesia were tested using von Frey filaments (10 and 200 mN) applied to the plantar surface of the paw. Changes in the blood flow were blocked significantly by intrathecal bumetanide at 10 and 100 μM in both pre- and posttreatment studies. Spinal bumetanide at 10 and 100 μM blocked neurogenic edema when it was administered before CAP injection, but only bumetanide at 100 μM administered after CAP injection reduced the paw edema significantly. Furthermore, the administration of bumetanide onto the spinal cord reduced the increment in DRR activity produced by CAP. Finally, both secondary mechanical allodynia and hyperalesia were reduced by bumetanide at 1, 10, and 100 μM. Taken together these results suggest that NKCC is involved in the increases in DRR activity, neurogenic inflammation and hyperalgesia and allodynia induced by intradermal CAP.

scholarly journals BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals

2014 ◽  
Vol 39 (9) ◽  
pp. 1439-1454 ◽  
Author(s):  
Wenling Chen ◽  
Wendy Walwyn ◽  
Helena S. Ennes ◽  
Hyeyoung Kim ◽  
James A. McRoberts ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nmda Receptors ◽  
Primary Afferent ◽  
Afferent Terminals
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