Neuropeptide tyrosine and pain

Brumovsky, Pablo Rodolfo; Shi, Tie‐Jun Sten; Landry, Marc; Villar, Marcelo J.; Hökfelt, Tomas

doi:10.1016/j.tips.2006.12.003

Cited by 98 publications

(116 citation statements)

References 91 publications

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“…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)(11)(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)(14)(15).…”

mentioning

confidence: 99%

Tonic inhibition of chronic pain by neuropeptide Y

Solway

Bose

Corder

et al. 2011

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

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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mentioning

confidence: 99%

Tonic inhibition of chronic pain by neuropeptide Y

Solway

Bose

Corder

et al. 2011

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

115

125

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“…Another hypothesis capable of explaining the relationship between constipation and MPS may be related to the "convergenceprojection" theory of the referred visceral sensitivity that assumes input from both somatic and visceral structures onto the same second order spinal neuron [44]. This theory has been well documented clinically and extensively researched in visceral disease studies, where it is termed "cross-organ sensitization" [18,45].…”

Section: Discussionmentioning

confidence: 99%

Constipation in patients with myofascial pain syndrome as important aspect for clinical and nutritional treatment: A case-control study

et al. 2017

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A B S T R A C T ObjectiveTo identify the occurrence of constipation in patients with myofascial pain syndrome and to correlate these disorders with the clinical and nutritional variables. MethodsThis report describes a case-control study performed with 98 adults of both sexs, including 49 patients and 49 individuals without pain. The intensity of the reported pain was evaluated using the Pain Visual Analog Scale, which provided a simple and efficient measurement of pain intensity consisting of a 10cm horizontal line with Revista de NutriçãoRev. Nutri., Campinas, 30(5):567-581, set./out., 2017 https://doi.org/10.1590/1678-98652017000500003 568 JA BARROS-NETO et al.the ends marked "absence of pain" and "worst possible pain". The occurrence of constipation was evaluated using the Rome III criteria. A multivariate linear regression was proposed to investigate risk factors between the frequency of bowel movements per week and independent variables this study. ResultsThe mean ages of the patients and controls were 45.9 (7.6) years and 41.2 (12.2) years, respectively. The intensity of the reported pain showed a mean of 7.3 (1.6) points. The likelihood of exhibiting constipation was 4.5 times higher in the patients than in the controls (p=0.001). The number of stools per week was negatively correlated with the intensity of the reported pain (r=-0.613, p<0.001). The use of benzodiazepines was negatively correlated with the frequency of bowel movements per week, while the use of muscle relaxants appeared to increase the frequency of defecation when combined with the use of benzodiazepines and adjusted for the intake of fiber, water and sexs (p=0.037). ConclusionConstipation was a frequent nosological entity in this patient population and the persistence of a change in intestinal motility showed a significant correlation with the pain intensity and low water intake. The reduction of the number of stools per week seems to be associated with the use of benzodiazepines.Keywords: Chronic pain. Constipation. Myofascial pain syndromes. (r=-0,613, p<0,001 R E S U M O Objetivo Identificar a ocorrência de constipação em pacientes com síndrome dolorosa miofascial e correlacionar essa desordem da motilidade intestinal com variáveis clínicas e nutricionais. Métodos Trata-se de um estudo de caso-controle, realizado com 98 indivíduos adultos de ambos os sexos I N T R O D U C T I O NChronic pain is considered a serious and growing public health problem worldwide. Affected people require medical attention approximately five times more frequently than the rest of the population. These patients have impaired physical, mental and social wellbeing, resulting in disability and work absenteeism [1,2].Myofascial Pain Syndrome (MPS) is characterized by regional chronic muscle pain located in a single muscle or in muscle groups.Revista de Nutrição Rev. Nutri., Campinas, 30(5):567-581, set./out., 2017 CONSTIPATION IN PATIENTS WITH MYOFASCIAL PAIN SYNDROME 569

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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%

“…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. Germ-line knockout of Y1 receptors or conditional knockdown of NPY is associated with thermal, chemical and mechanical hyperalgesia [6,[113][114][115][116]. Peripheral inflammation leads to an upregulation of Y1 receptors in spinal afferent neurons and in the dorsal horn of the spinal cord [117].…”

Section: Effect Of Npy To Inhibit Nociceptive Transmissionmentioning

confidence: 99%

“…While these studies have primarily focused on somatic pain, it remains to be investigated whether the NPY/Y receptor system also plays a role in the impact of the gut microbiota on visceral pain sensitivity [66][67][68][69][70]. Two major mechanisms whereby NPY controls pain transmission in the spinal cord have been envisaged: inhibition of transmitter release from the terminals of primary afferent neurons, mediated primarily by Y2 receptors, and inhibition of postsynaptic neurons in the dorsal horn, mediated primarily by Y1 receptors [113,114].…”

Section: Effect Of Npy To Inhibit Nociceptive Transmissionmentioning

confidence: 99%

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Neuropeptides and the Microbiota-Gut-Brain Axis

Holzer

Farzi

2014

Advances in Experimental Medicine and Biology

367

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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Neuropeptide tyrosine and pain

Cited by 98 publications

References 91 publications

Tonic inhibition of chronic pain by neuropeptide Y

Tonic inhibition of chronic pain by neuropeptide Y

Constipation in patients with myofascial pain syndrome as important aspect for clinical and nutritional treatment: A case-control study

Neuropeptides and the Microbiota-Gut-Brain Axis

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