Role of substance P signaling in enhanced nociceptive sensitization and local cytokine production after incision

Sahbaie, Peyman; Shi, Xiaoshuang; Guo, Tian-Zhi; Qiao, Yanli; Yeomans, David C.; Kingery, Wade S.; Clark, J. David

doi:10.1016/j.pain.2009.06.037

Cited by 108 publications

(99 citation statements)

References 61 publications

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“…Thus, these data confirm that, as expected, the scratch stimulus was sufficiently to deplete SP; and 30 minutes, relatively long period, was not enough time for a functional replenishment of the nerve ending. This period of time supports the importance of SP nociceptive sensitization after an incision, and potentially participates directly in modulating the intensity of inflammatory response in periincisional tissue [37].…”

Section: Discussionsupporting

confidence: 68%

“…The second hypothesis, the less likely, in the case of pro-CGRP, paradoxically to the SP, the scratch stimulus did not cleaved pro-CGRP and, in this case, it would not be possible to detect the replenishment time to pro-CGRP in nerve endings. However, conceptually [38,40], nociceptive stimuli release neuropeptides in a global way and, in the case of SP and CGRP one co-releases another in the same nerve ending. Thus, it would be really unlikely the second hypothesis.…”

Section: Discussionmentioning

confidence: 99%

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Reaction time and replenishment time of SP and CGRP after incision in rat skin

et al. 2014

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Background. The skin neurogenic inflammation is mainly related to Substance P (SP) and Calcitonin Gene-related Peptide (CGRP). There is no data on their availability in the dynamics of skin nerve endings, concerning their release and replenishment after a nociceptive stimulus, so this was investigated. Materials and methods. 25 rats were randomly distributed in 5 groups. The animals of the control group (CG) determined the baseline levels of neuropeptides in the skin. The groups S0 and S30 did not receive any cutaneous stimulus at 30 and 60 minutes, respectively. In the group S1, an “incision stimulus” was made at 30 minutes. In the group S31, a nociceptive stimulus was performed by subdermal scratching at 30 minutes and, at 60 minutes, the “incision stimulus” was carried out in the same location (“nociceptive hyperstimulation”). The skin samples of the other animals were harvested from the back 1 minute after their death. SP, pro-CGRP and CGRP were quantified by Western Blotting. Results. The “incision stimulus” released SP, S1 compared to S0 (p <0.05) detected in the first minute, and the replenishment time was more than 30 minutes. Also, it cleaved pro-CGRP, S1 compared to S31 (p <0.05) in the first minute, and its replenishment time less than 30 minutes. Release of CGRP was not detected. Conclusion. The incision released SP already detected in the first minute; its replenishment time is more than 30 minutes. The incision decreased pro-CGRP, also detected in the first minute; and its replenishment time is less than 30 minutes.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Reaction time and replenishment time of SP and CGRP after incision in rat skin

et al. 2014

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“…The phenomenon can be explained by a neurogenic inflammation following electrical stimulation. Activation of C-fibers stimulates the release of substance P and CGRP (calcitonin gene-related peptide) from small peptidergic neurons (Zieglgänsberger et al, 2005), and subsequent release of other inflammatory mediators including cytokines (Sahbaie et al, 2009). All these molecules can be good candidates to affect BSCB permeability.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Nerve Injury Alters Blood-Spinal Cord Barrier Functional and Molecular Integrity through a Selective Inflammatory Pathway

Echeverry¹,

Shi²,

Rivest³

et al. 2011

Journal of Neuroscience

215

201

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Peripheral nerve lesion triggers alterations in the spinal microenvironment that contribute to the pathogenesis of neuropathic pain. While neurons and glia have been implicated in these functional changes, it remains largely underexplored whether the blood-spinal cord barrier (BSCB) is also involved. The BSCB is an important component in the CNS homeostasis, and compromised BSCB has been associated with different pathologies affecting the spinal cord. Here, we demonstrated that a remote injury on the peripheral nerve in rats triggered a leakage of the BSCB, which was independent of spinal microglial activation. The increase of BSCB permeability to different size tracers, such as Evans Blue and sodium fluorescein, was restricted to the lumbar spinal cord and prominent for at least 4 weeks after injury. The spinal inflammatory reaction triggered by nerve injury was a key player in modulating BSCB permeability. We identified MCP-1 as an endogenous trigger for the BSCB leakage. BSCB permeability can also be impaired by circulating IL-1␤. In contrast, antiinflammatory cytokines TGF-␤1 and IL-10 were able to shut down the openings of the BSCB following nerve injury. Peripheral nerve injury caused a decrease in tight junction and caveolae-associated proteins. Interestingly, ZO-1 and occludin, but not caveolin-1, were rescued by TGF-␤1. Furthermore, our data provide direct evidence that disrupted BSCB following nerve injury contributed to the influx of inflammatory mediators and the recruitment of spinal blood borne monocytes/macrophages, which played a major role in the development of neuropathic pain. These findings highlight the importance of inflammation in BSCB integrity and in spinal cord homeostasis.

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“…could relieve allodynia for 6 h following hind paw incision. 13 Also, Preprotachykinin A (ppt-A − / − ) gene knockout mice showed persistently low level of allodynia after hind paw incision (up to day 2), although thermal hyperalgesia was transiently decreased.…”

Section: Nk1 Receptor and Nociceptionmentioning

confidence: 99%

“…10 Previous reports indicate that peripheral release of SP is related to nociception following neuropathy, 11 fractures 12 and hind paw incision. 13 Involvement of SP at the level of superficial laminae (Rexed's laminae I-II) of the spinal cord is well established in animal models of nociception. 4,14,15 Among the various preclinical pain models, the hind paw incision model is representative of postoperative pain.…”

Section: Introductionmentioning

confidence: 99%

Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat

et al. 2015

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Objectives: Noxious stimuli activate small to medium-sized dorsal root ganglion (DRG) neurons. Intense noxious stimuli result in the release of substance P (SP) from the central terminals of these neurons. It binds to the neurokinin type 1 receptor (NK1r) and sensitises the dorsal horn neurons. SP is also released from the peripheral terminals leading to neurogenic inflammation. However, their individual contribution at spinal and peripheral levels to postincisional nociception has not been delineated as yet. Methods: Sprague-Dawley rats were administered different doses (3-100 μg) of an NK1r antagonist (L760735) by intrathecal (i.t.) route before hind paw incision. On the basis of its antinociceptive effect on guarding behaviour, the 30 μg dose was selected for further study. In different sets of animals, this was administered i.t. (postemptive) and intrawound (i.w.). Finally, in another group, drug (30 μg) was administered through both i.t and i.w. routes. The antinociceptive effect was assessed and compared. Expression of SP was examined in the spinal cord. Intrawound concentration of SP and inflammatory mediators was also evaluated. Results: Postemptive i.t. administration significantly attenuated guarding and allodynia. Guarding was alone decreased after i.w. drug treatment. Combined drug administration further attenuated all nociceptive parameters, more so after postemptive treatment. Expression of SP in the spinal cord decreased post incision but increased in the paw tissue. Inflammatory mediators like the nerve growth factor also increased after incision. Conclusion: In conclusion, SP acting through the NK1r appears to be an important mediator of nociception, more so at the spinal level. These findings could have clinical relevance.

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Role of substance P signaling in enhanced nociceptive sensitization and local cytokine production after incision

Cited by 108 publications

References 61 publications

Reaction time and replenishment time of SP and CGRP after incision in rat skin

Reaction time and replenishment time of SP and CGRP after incision in rat skin

Peripheral Nerve Injury Alters Blood-Spinal Cord Barrier Functional and Molecular Integrity through a Selective Inflammatory Pathway

Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat

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