Peripheral hyperalgesia in experimental neuropathy: exacerbation by neuropeptide Y

Tracey, David J.; Romm, Michael A.; Yao, Nancy N.L.

doi:10.1016/0006-8993(94)01265-j

Cited by 69 publications

(39 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with pronociception, after long-term intrathecal administration of NPY, or a Y1 but not a Y2 agonist, nerve injury-induced hyperalgesia was exacerbated (White, 1997), and there is a Y1 receptor-dependent enhancement of calcium influx in vagal sensory neurons (Wiley et al, 1993). Moreover, subcutaneous injection of NPY, Y1R, or Y2R agonists increased mechanical hyperalgesia, although the application of Y1R agonists relieved thermal hyperalgesia (Tracey et al, 1995). Also, NPY, when acting on peripheral Y2Rs, was shown to be an important player in the sympathetically dependent neurogenic inflammation induced by intradermal capsaicin in rats (Lin et al, 2004).…”

Section: Npyergic Mechanisms and Painsupporting

confidence: 67%

Neuropeptide Y2 receptor protein is present in peptidergic and nonpeptidergic primary sensory neurons of the mouse

Brumovsky

Stanić

Shuster³

et al. 2005

J of Comparative Neurology

View full text Add to dashboard Cite

The localization of the neuropeptide tyrosine (NPY) Y2 receptor (Y2R) protein was studied in mouse dorsal root ganglia (DRGs) and spinal cord, by using a recently developed rabbit anti-Y2R antibody and a sensitive immunohistochemical method. Y2R-like immunoreactivity (-LI) was observed in about 10% of the small/medium-sized lumbar DRG neurons. Among these, about 44% were calcitonin gene-related peptide-immunoreactive, and about 38% bound isolectin B4. In the dorsal horn of the spinal cord, an intense Y2R-LI was seen in the most superficial layers, mostly restricted to laminae I-II. This immunoreactivity was completely abolished by dorsal rhizotomy. Y2R-L1 was also detected on the skin, more abundantly in hairy than glabrous skin. Specificity experiments showed complete disappearance of the Y2R-LI described above after incubation with antibody preadsorbed with the immunogenic peptide. Furthermore, Y2R-LI was also absent in a Y2R knockout mouse. These results demonstrate that the NPY Y2R is associated mainly with both peptidergic and nonpeptidergic small, presumably nociceptive, neurons projecting to the superficial layers of the dorsal horn. The results also support a role for this receptor and NPY in pain mechanisms.

show abstract

Section: Npyergic Mechanisms and Painsupporting

confidence: 67%

Neuropeptide Y2 receptor protein is present in peptidergic and nonpeptidergic primary sensory neurons of the mouse

Brumovsky

Stanić

Shuster³

et al. 2005

J of Comparative Neurology

View full text Add to dashboard Cite

show abstract

“…Clinical and experimental studies revealed that sympathetic modulation plays a critical role under conditions of neuropathy or neurogenic inflammation in peripheral nerves or tissues (Green et al 1993;Kim and Chung 1991;Lin et al 2003Moon et al 1999;Ren et al 2005a;Xie et al 1995) by a mechanism of sympathetic-sensory interactions in DRG neurons (Chung et al 1996;Devor et al 1994), the site of nerve injury (Devor and Seltzer 1999), and the skin (Sato and Perl 1991). The release of adrenergic and/or nonadrenergic transmitters is suggested to be the mechanism underlying the interactions because these substances have been well documented to play roles in nociception (Dowd et al 1998;Drummond 1995Drummond , 1998Lee et al 1999;Tracey et al 1995). Critically, these substances were shown to be colocalized in the synaptic vesicles of the postganglionic sympathetic nerve terminals and coreleased into the extracellular space to participate in several pathophysiological processes, including pathological pain signaling (Abbracchio and Burnstock 1998;Burnstock 1990Burnstock , 1996Park et al 2000;Sneddon et al 1996).…”

Section: Discussionmentioning

confidence: 99%

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

Ren¹,

Zou²,

Li³

et al. 2006

Journal of Neurophysiology

View full text Add to dashboard Cite

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.

show abstract

“…The functional significance of an increase in ''prejunctional'' receptors or sympathetic neurons after Axo is unclear. NPY has been shown to contribute to peripheral hyperalgesia by acting on prejunctional Y2Rs on postganglionic sympathetic terminals (38), which could be present at high levels on sympathetic fibers regenerating after Axo.…”

Section: Discussionmentioning

confidence: 99%

Expression and regulation of the neuropeptide Y Y2 receptor in sensory and autonomic ganglia

Zhang

Shi

Holmberg

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

112

View full text Add to dashboard Cite

The Y2 subtype of neuropeptide tyrosine (NPY) receptors (Y2R) and some neuropeptides have been studied with in situ hybridization in sensory and autonomic neurons of rat and monkey. Between 10% and 20% of the lumbar dorsal root ganglion (DRG) neuron profiles (NPs) contain Y2R mRNA in the rat and monkey. In rat DRGs Y2R mRNA is expressed in calcitonin gene-related peptide (CGRP)-positive, medium-sized, and large neurons, that is in a complementary fashion to the Y1R that is located in small CGRP neurons. In monkey DRGs Y2R mRNA is expressed mainly in small neurons. Peripheral axotomy up-regulates the Y2R in small and large DRG neurons in both species. Y2R and NPY mRNAs are colocalized in many large neurons in axotomized rat DRGs. Y2R mRNA is expressed in 50% of the NPs in the nodose ganglion with a modest increase after axotomy. Y2R mRNA is detected in a few NPs in normal rat superior cervical ganglia, with a marked increase after transection of the carotid nerves. No Y2R mRNA-positive, but many (Ϸ30%) weakly Y1R mRNA-positive NPs were found in the sphenopalatine ganglion. Finally, Y2R mRNA levels increase in rat spinal motoneurons after axotomy. Thus, under normal circumstances NPY may act on Y1 and Y2Rs expressed, respectively, in small and large CGRP-positive DRG neurons in the rat. Y2R may be an important receptor in the viscero-sensory neurons. Y2Rs may be particularly important after axotomy serving as presynaptic and͞or autoreceptors on rat DRG, superior cervical ganglion, and nodose ganglion neurons and as presynaptic receptors in monkey DRG neurons.Neuropeptide tyrosine (NPY), isolated from bovine brain by Tatemoto et al. (1), has a wide distribution in the nervous system and seems to be involved in multiple peripheral and central functions (2, 3). Based on pharmacological and binding studies using peptide fragments, evidence for the existence of multiple NPY receptor subtypes has been presented (4, 5). Two major subtypes were early recognized, the Y1 and the Y2 receptors (Y1Rs, Y2Rs) that were considered to represent primarily postjunctional and prejunctional receptors, respectively (6, 7). Y1R (8-10) and Y2R (11-13) have been cloned, and there may exist five further NPY receptor subtypes (5).There is evidence that NPY may play a role at the spinal level. Thus, NPY-positive local neurons are present in the dorsal horn (14), but in dorsal root ganglion (DRG) neurons NPY is under normal circumstances undetectable, or present at very low levels (15). A dramatic up-regulation of this peptide occurs in DRG neurons after peripheral nerve injury, primarily in large neurons (16 (18). Using in situ hybridization, Y1R mRNA was found in a population of mainly small DRG neurons also containing calcitonin gene-related peptide (CGRP) and substance P (SP) (21), but this receptor does not appear to be transported centrifugally, thus representing a purely somatic receptor (22). Moreover, after peripheral Axo, Y1R mRNA levels decreased in small but increased in large DRG neurons (21). In the autonomic nervous sys...

show abstract

Peripheral hyperalgesia in experimental neuropathy: exacerbation by neuropeptide Y

Cited by 69 publications

References 50 publications

Neuropeptide Y2 receptor protein is present in peptidergic and nonpeptidergic primary sensory neurons of the mouse

Neuropeptide Y2 receptor protein is present in peptidergic and nonpeptidergic primary sensory neurons of the mouse

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

Expression and regulation of the neuropeptide Y Y2 receptor in sensory and autonomic ganglia

Contact Info

Product

Resources

About