P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy

Hsieh, Yu-Lin; Hao, Cui; Lue, June‐Horng; Hsieh, Sung‐Tsang

doi:10.1016/j.expneurol.2012.02.013

Cited by 45 publications

(98 citation statements)

References 37 publications

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“…A317491, a selective antagonist of P2X3R, was used subcutaneously to treat colitis in the rats [27]. On the 3rd day after TNBS injection, rats were given saline (500 μl) or A317491…”

Section: Involvement Of P2x3 Receptors In Tnbs-induced Colitis Ratsmentioning

confidence: 99%

“…In colitis, more internal ATP was produced and expression of P2X3R at the end of colorectal nerves was also increased, thus leading to hypersensitivity of rectocolon [23][24][25]. When using the antagonists of P2X3R, 2′(3′)-O-(2,4,6-trinitrophenyl) ATP (TNP-ATP) or A317491, the expression and function of P2X3R in DRG were inhibited, resulting in the reduction of hypersensitivity in chronic inflammatory pain [26,27]. Also, after knockout of P2X3R in a mouse model of inflammatory bowel disease (IBD), visceral motor responses were decreased, improving inflammatory symptoms [24].…”

Section: Introductionmentioning

confidence: 99%

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Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

Jiang

Sun

et al. 2016

Purinergic Signalling

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Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041. In 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, weight loss, higher DAI scores, increased visceromotor responses, and inflammatory responses were reversed by application of DPN or ERB-041. The higher expressions of P2X3R in dorsal root ganglia (DRG) of CFA-treated rats and those in rectocolon and DRG of TNBS-treated rats were all decreased by injection of DPN or ERB-041. DPN application also inhibited P2X3R-evoked inward currents in DRG neurons from TNBS rats. Mechanical hyperalgesia and increased P2X3 expression in ovariectomized (OVX) CFA-treated rats were reversed by estrogen replacements. Furthermore, the expressions of extracellular signal-regulated kinase (ERK) in DRG and spinal cord dorsal horn (SCDH) and c-fos in SCDH were significantly decreased after estrogen replacement compared with those of OVX rats. The ERK antagonist U0126 significantly reversed mechanical hyperalgesia in the OVX rats. These results suggest that estrogen may play an important therapeutic role in inflammation through downregulation of P2X3R in peripheral tissues and the nervous system, probably via ERβ, suggesting a novel therapeutic strategy for clinical treatment of inflammation.

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“…A317491, a selective antagonist of P2X3R, was used subcutaneously to treat colitis in the rats [27]. On the 3rd day after TNBS injection, rats were given saline (500 μl) or A317491…”

Section: Involvement Of P2x3 Receptors In Tnbs-induced Colitis Ratsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

Jiang

Sun

et al. 2016

Purinergic Signalling

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“…α 1 -AR expression was up-regulated on nerve fibers co-labelled with CGRP + or IB4 + , and was also upregulated in nerve bundles on fibers co-labelled with NF200, a marker of myelinated nociceptive and non-nociceptive neurons. These nerve fibers may carry different types of pain information; CGRP + nociceptors respond to noxious heat and are partly responsible for hypersensitivity to heat after nerve injury 17,30 , whereas non-peptidergic nociceptors respond both to noxious heat and mechanical stimuli and contribute to heat hypersensitivity and mechanical allodynia after nerve injury 16,41,42,45,46 . Similarly, decreases in the firing threshold of myelinated nociceptors may increase the intensity of sharp, pricking pain after nerve injury 8 .…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Increased Expression of Cutaneous α1-Adrenoceptors After Chronic Constriction Injury in Rats

Drummond¹,

Dawson²,

Finch³

et al. 2014

The Journal of Pain

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Alpha 1 -adrenoceptor expression on nociceptors may play an important role in sympathetic-sensory coupling in certain neuropathic pain syndromes. The aim of this study was to determine whether α 1 -adrenoceptor expression was up-regulated on surviving peptidergic, non-peptidergic and myelinated nerve fiber populations in the skin after chronic constriction injury of the sciatic nerve in rats. Seven days after surgery, α 1 -adrenoceptor expression was up-regulated in the epidermis and on dermal nerve fibres in plantar skin ipsilateral to the injury, but not around blood vessels. This α 1 -adrenoceptor up-regulation in the plantar skin was observed on all nerve fiber populations examined. However, α 1 -adrenoceptor expression was unaltered in dorsal hind paw skin after the injury. The increased expression of α 1 -adrenoceptors on cutaneous nociceptors in plantar skin after chronic constriction injury suggests that this may be a site of sensory-sympathetic coupling that increases sensitivity to adrenergic agonists after nerve injury. In addition, activation of up-regulated α 1 -adrenoceptors in the epidermis might cause release of factors that stimulate nociceptive signalling.Perspective: Our findings indicate that peripheral nerve injury provokes up-regulation of α 1 -adrenoceptors on surviving nociceptive afferents and epidermal cells in the skin. This might contribute to sympathetically maintained pain in conditions such as complex regional pain syndrome, painful diabetic neuropathy and post-herpetic neuralgia.

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“…RTX neuropathy was induced by following an established protocol [16,17]. Briefly, RTX (Sigma, St. Louis, MO, USA) was dissolved in the vehicle (10 % Tween 80 and 10 % ethanol in normal saline).…”

Section: Rtx Neuropathy and Apyrase Treatmentmentioning

confidence: 99%

“…We previously established a mouse model of resiniferatoxin (RTX) neuropathy with neuropathic pain resulting from degeneration of small-diameter nerves in the skin [16] and upregulation of P2X3 purinoceptors in DRGs and their corresponding nerve terminals [17]. The injury profiles of P2X3(+) DRG neuronal density in RTX neuropathy was linearly correlated with the degree of neuropathic pain behaviors [17]. This finding prompted us to ask two intriguing questions: in addition to P2X3 purinoceptor upregulation, whether endogenous ATP is released by the injured DRG and denervated skin tissues, and if so, does endogenous ATP modulate the development of neuropathic pain behaviors?…”

Section: Introductionmentioning

confidence: 99%

Enhancement of purinergic signalling by excessive endogenous ATP in resiniferatoxin (RTX) neuropathy

Lin

Hsiao

et al. 2012

Purinergic Signalling

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ATP is a ligand of P2X family purinoceptors, and exogenous ATP administration evokes pain behaviors. To date, there is a lack of systematic studies to address relationships between endogenous ATP and neuropathic pain. In this report, we took advantage of a mouse model of resiniferatoxin (RTX)-induced neuropathic pain to address the role of endogenous ATP in neuropathic pain. After RTX administration, endogenous ATP markedly increased in dorsal root ganglia (DRGs) (p <0.01) and skin tissues (p<0.001). The excessive endogenous ATP was removed by apyrase, an ATP hydrolyzing enzyme, administration via either a lumbar puncture route (p<0.001) or an intraplantar injection (p<0.001), which led to the normalization of neuropathic pain. In addition, intraplantar treatment with apyrase caused mechanical analgesia. Linear analyses showed that the densities of P2X3(+) neurons (r=−0.72, p<0.0001) and P2X3(+) dermal nerves (r=−0.72, p< 0.0001) were inversely correlated with mechanical thresholds. Moreover, the contents of endogenous ATP in skin tissues were linearly correlated with P2X3(+) dermal nerves (r=0.80, p<0.0001) and mechanical thresholds (r=−0.80, p<0.0001). In summary, this study demonstrated that enhanced purinergic signalling due to an increase in endogenous ATP after RTX-induced nerve injury contributed to the development of neuropathic pain. The data in this report provide a new therapeutic strategy for pain control by targeting the endogenous ligand of purinergic signalling.

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P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy

Cited by 45 publications

References 37 publications

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

Increased Expression of Cutaneous α1-Adrenoceptors After Chronic Constriction Injury in Rats

Enhancement of purinergic signalling by excessive endogenous ATP in resiniferatoxin (RTX) neuropathy

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