Time-dependent changes in bolton-hunter-labeled125I-substance P binding in rat spinal cord following unilateral adjuvant-induced peripheral inflammation

Stucky, Cheryl L.; Galeazza, M.T.; Seybold, Virginia S.

doi:10.1016/0306-4522(93)90071-m

Cited by 49 publications

(10 citation statements)

References 65 publications

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“…Unless there is incredibly rapid turnover of the receptor, this result suggests that an SP-NK-1 receptor interaction does not come into play in the basal firing of spinal cord neurons. This is true despite the fact that SP levels and the affinity of the NK-1 receptor increase during the development of inflammation (Stucky et al, 1993). We conclude that the upregulation of the NK-1 receptor is only functionally manifested when a stimulus is superimposed on a background of inflammation-induced alterations in the dorsal horn.…”

Section: Nk-1 Receptor Internalization In the Setting Of Inflammationmentioning

confidence: 69%

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

et al. 1997

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Although the neurokinin-1 (NK-1)/substance P (SP) receptor is expressed by neurons throughout the spinal dorsal horn, noxious chemical stimulation in the normal rat only induces internalization of the receptor in cell bodies and dendrites of lamina I. Here we compared the effects of mechanical and thermal stimulation in normal rats and in rats with persistent hindpaw inflammation. Electron microscopic analysis confirmed the upregulation of receptor that occurs with inflammation and demonstrated that in the absence of superimposed stimulation, the increased receptor was, as in normal rats, concentrated on the plasma membrane. In general, noxious mechanical was more effective than noxious thermal stimulation in inducing NK-1 receptor internalization, and this was increased in the setting of inflammation. Although a 5 sec noxious mechanical stimulus only induced internalization in 22% of lamina I neurons in normal rats, after inflammation, it evoked near-maximal (98%) internalization in lamina I, produced significant changes in laminae III-VI, and expanded the rostrocaudal distribution of neurons with internalized receptor. Even non-noxious (brush) stimulation of the inflamed hindpaw induced internalization in large numbers of superficial and deep neurons. For thermal stimulation, the percentage of cells with internalized receptor increased linearly at Ͼ45°C, but in normal rats, these were restricted to lamina I. After inflammation, however, the 52°C stimulus also induced internalization in 25% of laminae III-IV cells. These studies provide a new perspective on the reorganization of dorsal horn circuits in the setting of persistent injury and demonstrate a critical contribution of SP.

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Section: Nk-1 Receptor Internalization In the Setting Of Inflammationmentioning

confidence: 69%

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

et al. 1997

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“…Tachykinin receptor 1 (NK1 receptor) and its primary ligand, substance P, also play a role in pain and sensation [45,56,57]. In addition to substance P release at the spinal cord during injury, substance P is also released from the sensory nerve endings into the peripheral tissues, consequently contributing to cutaneous neurogenic inflammation [51].…”

Section: Discussionmentioning

confidence: 99%

Cold hypersensitivity increases with age in mice with sickle cell disease

Zappia

Garrison

Hillery

et al. 2014

Pain

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Sickle cell disease (SCD) is associated with acute vaso-occlusive crises that trigger painful episodes and frequently involves ongoing, chronic pain. Additionally, both humans and mice with SCD experience heighted cold sensitivity. However, studies have not addressed the mechanism(s) underlying the cold sensitization, nor its progression with age. Here we measured thermotaxis behavior in young and aged mice with severe SCD. Sickle mice had a marked increase in cold sensitivity measured by a cold preference test. Further, cold hypersensitivity worsened with advanced age. We assessed whether enhanced peripheral input contributes to the chronic cold pain behavior by recording from C fibers, many of which are cold-sensitive, in skin-nerve preparations. We observed that C fibers from sickle mice displayed a shift to warmer (more sensitive) cold-detection thresholds. To address mechanisms underlying the cold sensitization in primary afferent neurons, we quantified mRNA expression levels for ion channels thought to be involved in cold detection. These included the Transient Receptor Potential Melastatin 8 (Trpm8) and TRP Ankyrin 1 (Trpa1) channels, as well as the two-pore domain potassium channels, TREK-1 (Kcnk2), TREK-2 (Kcnk4), and TRAAK (Kcnk10). Surprisingly, transcript expression levels of all of these channels were comparable between sickle and control mice. We further examined transcript expression of 83 additional pain-related genes and found increased mRNA levels for endothelin 1 and tachykinin receptor 1. These factors may contribute to hypersensitivity in sickle mice at both the afferent and behavioral levels. Sensory neurons from sickle cell disease mice are sensitized to cold, mirroring behavioral observations, and have increased expression of endothelin 1 and tachykinin receptor 1.

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“…NGF, by increasing the level of these peptides in the sensory neurone, may increase the capacity of afferents innervating inflamed tissue to produce central sensitization. The changes in peptide expression seen in the DRG during inflammation (Noguchi et al, 1988;Donaldson et al, 1992;Donnerer et al, 1992;Smith et al, 1992;Woolf et al, 1994) are reflected in an increase in levels in the dorsal horn (Oku et al, 1987;Schaible et al, 1990) and by an increase in peptide receptor/binding sites in this area (Kar et al, 1993;Schafer et al, 1993;Stucky et al, 1993) (Hong et al, 1993) and adrenalectomy results in an increase in substance P and CGRP content in rat DRG (Smith et al, 1991 (Kieselbach et al, 1993). An inhibitory effect of glucocorticoids on IL-l 1 production is fairly well characterized (Snyder & Unanue, 1982;Lee et al, 1988;Dawson et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

Safieh‐Garabedian

Poole

Allchorne

et al. 1995

British J Pharmacology

556

324

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Peripheral inflammation is associated with the local production of neuroactive inflammatory cytokines and growth factors. These may contribute to inflammatory pain and hyperalgesia by directly or indirectly altering the function or chemical phenotype of responsive primary sensory neurones. To investigate this, inflammation was produced by the intraplantar injection of complete Freund's adjuvant (CFA) in adult rats. This resulted in a significant elevation in interleukin‐ip (IL‐1β) and nerve growth factor (NGF) levels in the inflamed tissue and of the peptides, substance P and calcitonin gene‐related peptide (CGRP) in the L4 dorsal root ganglion 48 h post CFA injection. The effects of a steroidal (dexamethasone) and a non‐steroidal (indomethacin) anti‐inflammatory drug on the levels of NGF and IL‐1β in inflamed tissue were investigated and compared with alterations in behavioural hyperalgesia and neuropeptide expression in sensory neurones. Systemic dexamethasone (120 μg kg−1 per day starting the day before the CFA injection) had no effect on the inflammatory hyperalgesia. When the dose was administered 3 times daily, a reduction in mechanical and to a lesser extent thermal sensitivity occurred. Indomethacin at 2 mg kg−1 daily (i.p.) had no effect on the hyperalgesia and a dose of 4 mg kg−1 daily was required to reduce significantly mechanical and thermal hypersensitivity. The increase in NGF produced by the CFA inflammation was prevented by both dexamethasone and indomethacin, but only at the higher dose levels. Dexamethasone at the lower and higher dose regimes diminished the upregulation of IL‐1β whereas indomethacin had an effect only at the higher dose. The increase in SP and CGRP levels produced by the CFA inflammation was prevented by dexamethasone and indomethacin at the lower and higher dose regimes. Intraplantar injections of IL‐1β (0.01, 0.1 and 1 ng) produced a brief (6 h) thermal hyperalgesia and an elevation in cutaneous NGF levels which was prevented by pretreatment with human recombinant IL‐1 receptor antagonist (IL‐1 ra) (0.625 μg, i.v.). The thermal hyperalgesia but not the NGF elevation produced by intraplantar IL‐1β (1 ng) was prevented by administration of a polyclonal neutralizing anti‐NGF serum. IL‐1 ra significantly reduced the mechanical hyperalgesia produced by CFA for 6 h after administration as well as the CFA‐induced elevation in NGF levels. Anti‐NGF pretreatment substantially reduced CFA‐induced mechanical and thermal hyperalgesia without reducing the elevation in IL‐1β. Intraplantar NGF (0.O2, 0.2 and 2 μg) injections produced a short lasting thermal and mechanical hyperalgesia but did not change IL‐1β levels in the hindpaw skin. Our results demonstrate that IL‐1β contributes to the upregulation of NGF during inflammation and that NGF has a major role in the production of inflammatory pain hypersensitivity.

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Time-dependent changes in bolton-hunter-labeled125I-substance P binding in rat spinal cord following unilateral adjuvant-induced peripheral inflammation

Cited by 49 publications

References 65 publications

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

Cold hypersensitivity increases with age in mice with sickle cell disease

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

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