Spinal mechanisms of NPY analgesia

Smith, Peter A.; Moran, Timothy D.; Abdulla, Fuad; Tumber, Kiranjeet K.; Taylor, Bradley K.

doi:10.1016/j.peptides.2006.09.029

Cited by 73 publications

(78 citation statements)

References 75 publications

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“…1D). Such results have led to the hypothesis that inflammatory or sensory nerve injury increases NPY signaling at the dorsal horn, thereby inhibiting pronociceptive neurotransmission (20). Continuous exposure to Dox (in the drinking water), begun 14 d after SNI, essentially silenced NPY expression in dorsal horn (P < 0.01) (Fig.…”

Section: Resultsmentioning

confidence: 92%

“…The intensity and duration of this central sensitization is determined by the net activity of local excitatory and inhibitory neurotransmitter systems, together with ongoing/evoked primary afferent activity and descending supraspinal control (20,25). Spinal endogenous inhibitory systems serve as opposing compensatory influences, and the current study is indicative of the powerful capacity of the NPY receptor system to restrain allodynia and hyperalgesia for extended time periods.…”

Section: Discussionmentioning

confidence: 88%

“…Y1-ir is found in cells and terminals of lamina II i , whereas Y2-ir is found in terminals of I-II o (13)(14)(15). Numerous studies using an intrathecal delivery approach have demonstrated that exogenous delivery of NPY reduces hypersensitivity to tactile and thermal stimulation in models of chronic pain, including the spared nerve injury (SNI) model of neuropathic pain; Y1 and Y2 receptor antagonists reverse these antiallodynic actions (16)(17)(18)(19)(20). However, the use of receptor-selective antagonists to evaluate the intrinsic actions of NPY is uncommon, perhaps because behavioral thresholds demonstrate a floor effect in major animal models.…”

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confidence: 99%

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Tonic inhibition of chronic pain by neuropeptide Y

Solway

Bose

Corder

et al. 2011

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

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115

125

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Dramatically up-regulated in the dorsal horn of the mammalian spinal cord following inflammation or nerve injury, neuropeptide Y (NPY) is poised to regulate the transmission of sensory signals. We found that doxycycline-induced conditional in vivo (Npy tet/tet ) knockdown of NPY produced rapid, reversible, and repeatable increases in the intensity and duration of tactile and thermal hypersensitivity. Remarkably, when allowed to resolve for several weeks, behavioral hypersensitivity could be dramatically reinstated with NPY knockdown or intrathecal administration of Y1 or Y2 receptor antagonists. In addition, Y2 antagonism increased dorsal horn expression of Fos and phosphorylated form of extracellular signal-related kinase. Taken together, these data establish spinal NPY receptor systems as an endogenous braking mechanism that exerts a tonic, long-lasting, broad-spectrum inhibitory control of spinal nociceptive transmission, thus impeding the transition from acute to chronic pain. NPY and its receptors appear to be part of a mechanism whereby mammals naturally recover from the hyperalgesia associated with inflammation or nerve injury.N europeptide Y (NPY) is a 36-aa peptide that acts at Gprotein-coupled Y receptors to initiate cellular signaling. NPY systems modulate a variety of physiological processes, including somatosensation (1). Expressed in neurons and terminals of the spinal cord dorsal horn (2), and up-regulated by peripheral inflammation or nerve injury, NPY is poised to inhibit the spinal transmission of sensory signals. For example, nerve injury elicits a profound de novo synthesis of NPY in large-diameter neurons of dorsal root ganglion (DRG) and their terminal regions in the dorsal horn (3-7), perhaps serving as an adaptive compensatory response to increased excitatory signaling (8). Increases in NPY last at least 24 wk, indicating that it is temporally available to confer long-lasting inhibition of pronociceptive neurotransmission (9), but this hypothesis has not been tested.Of the five NPY receptors cloned in the mouse, only Y1 and Y2 are expressed in the adult DRG (they colocalize with peptides that are predominantly found in unmyelinated to thinly myelinated neurons) and dorsal horn (10-12). Y1-ir is found in cells and terminals of lamina II i , whereas Y2-ir is found in terminals of I-II o (13-15). Numerous studies using an intrathecal delivery approach have demonstrated that exogenous delivery of NPY reduces hypersensitivity to tactile and thermal stimulation in models of chronic pain, including the spared nerve injury (SNI) model of neuropathic pain; Y1 and Y2 receptor antagonists reverse these antiallodynic actions (16)(17)(18)(19)(20). However, the use of receptor-selective antagonists to evaluate the intrinsic actions of NPY is uncommon, perhaps because behavioral thresholds demonstrate a floor effect in major animal models. For example, although the Y1 receptor antagonist BIBO3304 slightly but significantly increased heat hyperalgesia when administered during the peak of complete Freund'...

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Section: Resultsmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

See 1 more Smart Citation

Tonic inhibition of chronic pain by neuropeptide Y

Solway

Bose

Corder

et al. 2011

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

Self Cite

115

125

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“…32) These anatomical findings indicate the importance of the NPY system in the development of pathological neuropathic pain. 33) Neuropathic pain is a form of chronic pain caused by nerve injury, disease states, or toxic insults. We evaluated the use of I. paraguariensis extract in a rat model of SNI to determine whether I. paraguariensis extract affected the expression of NPY.…”

Section: Discussionmentioning

confidence: 99%

Analgesic Effect of <i>Ilex paraguariensis</i> Extract on Postoperative and Neuropathic Pain in Rats

Lim

Kim

Han

et al. 2015

Biological & Pharmaceutical Bulletin

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Ilex paraguariensis, known as "Yerba Mate," is an herb used in a beverage that is widely consumed in southern Latin American countries. Furthermore, it has been traditionally used to treat depression, and as an analgesic to manage both nerve pain and headache. The pain-related experimental evidence regarding the analgesic effects of Mate is unclear. Therefore, this study was designed to investigate whether Mate extract exhibits analgesic effects in both the plantar incision and spared nerve injury (SNI) models in rats. We tested the mechanical withdrawal threshold (MWT) using von Frey filaments. We also tested pain-related behavior using ultrasonic vocalization (USV). Neuropeptide Y (NPY) and pain-related cytokines were also determined in the dorsal root ganglia in a rat model of SNI. Our results showed that oral administration of Mate extract significantly increased MWT values, and reduced the number of 22-27 kHz USVs 24 h after the plantar incision operation. Moreover, after 15 d of continuous treatment with Mate extract, the SNI-induced hypersensitivity, cytokine levels, and NPY expression were significantly reduced compared to the corresponding findings in the control group. These results suggest that the intake of Mate extract has potential as a treatment for both postoperative pain and neuropathic pain.

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“…Spinal afferent neurons, which contain low amounts of NPY, terminate in the spinal cord where interneurons and descending noradrenergic neurons express appreciable amounts of NPY [6,113,114]. An abundant occurrence of Y1 and Y2 receptors in the spinal cord enables NPY to play an important role in the processing of incoming nociceptive information.…”

Section: Effect Of Npy To Inhibit Nociceptive Transmissionmentioning

confidence: 99%

Neuropeptides and the Microbiota-Gut-Brain Axis

Holzer

Farzi

2014

Advances in Experimental Medicine and Biology

366

290

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Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gutbrain axis. Current efforts in elucidating the implication of neuropeptides in the microbiota-gutbrain axis address 4 information carriers from the gut to the brain (vagal and spinal afferent neurons; immune mediators such as cytokines; gut hormones; gut microbiota-derived signalling molecules) and 4 information carriers from the central nervous system to the gut (sympathetic efferent neurons; parasympathetic efferent neurons; neuroendocrine factors involving the adrenal medulla; neuroendocrine factors involving the adrenal cortex). Apart from operating as neurotransmitters, many biologically active peptides also function as gut hormones. Given that neuropeptides and gut hormones target the same cell membrane receptors (typically G proteincoupled receptors), the two messenger roles often converge in the same or similar biological implications. This is exemplified by NPY and peptide YY (PYY), two members of the PP-fold peptide family. While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides are likely to emerge as neural and endocrine messengers in orchestrating the microbiotagut-brain axis in health and disease.

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Spinal mechanisms of NPY analgesia

Cited by 73 publications

References 75 publications

Tonic inhibition of chronic pain by neuropeptide Y

Tonic inhibition of chronic pain by neuropeptide Y

Analgesic Effect of <i>Ilex paraguariensis</i> Extract on Postoperative and Neuropathic Pain in Rats

Neuropeptides and the Microbiota-Gut-Brain Axis

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