Topography and time course of changes in spinal neuropeptide Y immunoreactivity after spared nerve injury

Intondi, A.; Zadina, James E.; Zhang, X.; Taylor, Bradley K.

doi:10.1016/j.neuroscience.2009.10.052

Cited by 19 publications

(23 citation statements)

References 33 publications

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“…It might be due to the different animal models used for the respective studies (complete Freund's adjuvant-induced inflammation versus surgical incision). Changes in NPY expression also occurs in neuropathic pain though this is mainly localized in the deeper laminae (Rexed's laminae III-IV), which is in accordance with changes in the large diameter dorsal root ganglion neurons instead of the smaller sized cell soma observed after inflammatory pain [14]. Paw incision-induced nociception was comprehensively attenuated up to day 2 by intrathecal administration of morphine, considered to be the gold standard reference drug for the treatment of pain in patients [34].…”

Section: Discussionsupporting

confidence: 74%

“…However, expression of NPY in the spinal cord during the post-incision period was not studied. This could be important as definitive changes in NPY immunoreactivity was observed in specific sectors of the dorsal horn of the spinal cord after induction of neuropathic pain [14]. Consequently, the main objective of the present work was to characterize the temporospatial changes in the expression of NPY in the spinal cord of rats and to correlate this with post-incisional nociception.…”

Section: Introductionmentioning

confidence: 96%

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Involvement of Neuropeptide Y in Post-Incisional Nociception in Rats

et al. 2018

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Background: Neuropeptide Y (NPY) is abundantly distributed in the mammalian nervous system. Its role in nociception arising from inflammatory and neuropathic pain conditions has been elucidated. However, its involvement in post-incisional nociception, particularly at the spinal cord level, is relatively unknown. Purpose: Management of postoperative pain is suboptimal. Evaluation of changes at the spinal level could facilitate better understanding of neural mechanisms underlying this type of pain. Methods: Rats were subjected to hind paw incision and spatiotemporal pattern of NPY expression in the dorsal horn was investigated by immunohistochemistry. Next, rats were implanted with intrathecal catheters using previously standardized procedure. NPY was injected into the intrathecal space by an indwelling catheter and behavioral assessment of nociception was performed. Results: Higher expression of NPY was observed in the superficial laminae of the dorsal horn. After incision, specific changes were observed like an abrupt decrease at 3 h after incision, which could be correlated with the intense nociception at this time. In contrast to morphine administration, which attenuated all 3 behavioral parameters of nociception, NPY decreased guarding behavior and thermal hyperalgesia during the acute phase. Conclusions: NPY is extensively expressed in the superficial laminae of the spinal cord and exhibit marked changes after incision. Nociception is also decreased after its administration. Hence, it is likely involved in post-incisional nociception. This information could have clinical relevance.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 96%

Involvement of Neuropeptide Y in Post-Incisional Nociception in Rats

et al. 2018

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“…When initiated before tissue or nerve injury, knockdown increased the intensity of thermal hypersensitivity and the duration of tactile hypersensitivity. Whether this reflects intrinsic NPY-mediated attenuation of the development of hypersensitivity is unclear, in part because NPY expression studies have not reported changes before 3 or 14 d after inflammation (7) or nerve injury (3,8,9,28), respectively. When initiated after injury, knockdown produced a rapid, reversible, and repeatable increase in hypersensitivity (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…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)(4)(5)(6)(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.…”

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confidence: 99%

Tonic inhibition of chronic pain by neuropeptide Y

Solway

Bose

Corder

et al. 2011

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

118

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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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“…These stimuli are unique in that they fail to evoke a nocifensive response prior to injury [6]. Tactile or mechanical hyperalgesia is frequently measured as an exaggeration of the animal's nocifensive response to noxious stimuli, such as the pricking of the skin with sharp needle points [7]. Because the stimuli used are sufficient to exceed the pain threshold (PT) before the injury, pinprick stimuli are specific to the detection of mechanical hyperalgesia and analgesia and are not suited to the detection of allodynia or to the detection of the baseline PT.…”

Section: Introductionmentioning

confidence: 99%