Long-Lasting Regulation of Galanin, Opioid, and Other Peptides in Dorsal Root Ganglia and Spinal Cord during Experimental Polyarthritis

Calzà, Laura; Pozza, Monica; Arletti, Rossana; Manzini, E; Hökfelt, Tomas

doi:10.1006/exnr.2000.7442

Cited by 48 publications

(25 citation statements)

References 61 publications

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“…As noted above, opioid receptor density remained elevated for almost 3 months in a CFA model of rheumatoid polyarthritis, long after pain scores had recovered to baseline (Calza et al, 2000). …”

Section: Opioid Receptor-masked Sensitizationmentioning

confidence: 92%

“…This can be long lasting: autoradiography studies demonstrate that opioid receptor density remains elevated for almost 3 months in a complete Freund's adjuvant (CFA) model of rheumatoid polyarthritis (Calza et al, 2000). We recently reported that injury-induced MOR signaling does not necessarily dissipate over time, and can be maintained long enough to oppose chronic pain .…”

Section: Opioid Receptors and Endogenous Analgesiamentioning

confidence: 99%

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Endogenous Analgesia, Dependence, and Latent Pain Sensitization

Taylor

Corder

2014

Current Topics in Behavioral Neurosciences

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Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid analgesia, thus restricting LS within a state of remission; or b) extinguishing LS altogether.

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Section: Opioid Receptor-masked Sensitizationmentioning

confidence: 92%

Section: Opioid Receptors and Endogenous Analgesiamentioning

confidence: 99%

Endogenous Analgesia, Dependence, and Latent Pain Sensitization

Taylor

Corder

2014

Current Topics in Behavioral Neurosciences

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“…Furthermore, in chronic inflammation, upregulation of galanin messenger ribonucleic acid expression and galanin immunoreactivity in dorsal root ganglia (DRG) were observed in rats with adjuvant arthritis (Calza et al 2000). Accordingly, galanin-overexpressing transgenic mice showed a significant decrease in plasma extravasation upon activation of neurogenic inflammation after application of mustard oil, which activates sensory nerves (Holmberg et al 2005).…”

Section: Abbreviationsmentioning

confidence: 98%

Targeted Disruption of the Galanin Gene Attenuates Inflammatory Responses in Murine Skin

et al. 2007

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The release of neuropeptides from primary sensory nerve fibers has been implicated in the modulation of local immune responses in surface tissues, such as the skin and the gastrointestinal mucosa, thereby inducing neurogenic inflammation, which is characterized by plasma extravasation and vasodilatation. In addition, cytokines, either alone or in conjunction with neuropeptides, initiate recruitment of immunocompetent cells such as neutrophils during the initial phases of inflammation. Growing evidence suggests that the neuropeptide galanin plays an important role in skin immune defense and pathophysiology. In this paper, we report that adult mice carrying a loss-of-function mutation in the galanin gene (galanin knockout, Gal KO) demonstrate an absence of the normal neurogenic inflammatory response, upon treatment of the skin either with the vanilloid receptor 1 agonist capsaicin or noxious heat. Furthermore, a lack of an acute inflammatory edema induced by coinjection of substance P and calcitonin gene-related peptide was observed. In addition, Gal KO animals also exhibit a deficit in neutrophil accumulation in the skin after exposure to noxious heat, carrageenin, or tumor necrosis factor alpha. These data indicate that Gal KO mice demonstrate abnormal neurogenic inflammatory responses in murine skin compared to strain-matched wild-type mice.

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“…Indeed, alpha-CGRP null mice do not develop hyperalgesia responses to inflammatory insults (Salmon et al, 2001, Zhang et al, 2001). The neuropeptide calcitonin gene related peptide (CGRP) is increased in sensory neurons after peripheral inflammation (Donaldson et al, 1992, Smith et al, 1992, Donnerer et al, 1993, Nahin and Byers, 1994, Seybold et al, 1995, Neumann et al, 1996, Malcangio et al, 1997, Mulder et al, 1997b, Durham and Russo, 1999, Calza et al, 2000, Bulling et al, 2001 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript.…”

mentioning

confidence: 99%

Activin acts with nerve growth factor to regulate calcitonin gene-related peptide mRNA in sensory neurons

Hall

2007

Neuroscience

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Calcitonin Gene-Related Peptide (CGRP) increases in sensory neurons after inflammation and plays an important role in abnormal pain responses, but how this neuropeptide is regulated is not well understood. Both activin A and Nerve Growth Factor (NGF) increase in skin after inflammation and induce CGRP in neurons in vivo and in vitro. This study was designed to understand how neurons integrate these two signals to regulate the neuropeptide important for inflammatory pain. In adult dorsal root ganglion neurons, NGF but not activin alone produced a dose-dependent increase in CGRP mRNA. When added together with NGF, activin synergistically increased CGRP mRNA, indicating that sensory neurons combine these signals. Studies were then designed to learn if that combination occurred at a common receptor or shared intracellular signals. Studies with Activin IB receptor or trkA inhibitors suggested that each ligand required its cognate receptor to stimulate the neuropeptide. Further, activin did not augment NGF-initiated intracellular MAPK signals but instead stimulated Smad phosphorylation, suggesting these ligands initiated parallel signals in the cytoplasm. Activin synergy required several NGF intracellular signals to be present. Because activin did not further stimulate, but did require NGF intracellular signals, it appears that activin and NGF converge not in receptor or cytoplasmic signals, but in transcriptional mechanisms to regulate CGRP in sensory neurons after inflammation. Keywords inflammation; neuropeptides; ERK; SmadHyperalgesia is a key sign of inflammation and is initiated by signals from inflamed tissues that act on sensory neurons to modify molecules involved in pain behaviors. The central mechanism of hyperalgesia involves the hyperexcitablility of dorsal horn neurons, which can be attenuated by blocking glutamate receptors Inturrisi, 2001, Yashpal et al., 2001), neurokinin receptors (Malmberg and Yaksh, 1992, Thompson et al., 1994) and CGRP receptors (Sun et al., 2004) in the spinal cord. Indeed, alpha-CGRP null mice do not develop hyperalgesia responses to inflammatory insults (Salmon et al., 2001, Zhang et al., 2001). The neuropeptide calcitonin gene related peptide (CGRP) is increased in sensory neurons after peripheral inflammation (Donaldson et al., 1992, Smith et al., 1992, Donnerer et al., 1993, Nahin and Byers, 1994, Seybold et al., 1995, Neumann et al., 1996, Malcangio et al., 1997, Mulder et al., 1997b, Durham and Russo, 1999, Calza et al., 2000, Bulling et al., 2001 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Salmon et al., 2001, Zha...

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Long-Lasting Regulation of Galanin, Opioid, and Other Peptides in Dorsal Root Ganglia and Spinal Cord during Experimental Polyarthritis

Cited by 48 publications

References 61 publications

Endogenous Analgesia, Dependence, and Latent Pain Sensitization

Endogenous Analgesia, Dependence, and Latent Pain Sensitization

Targeted Disruption of the Galanin Gene Attenuates Inflammatory Responses in Murine Skin

Activin acts with nerve growth factor to regulate calcitonin gene-related peptide mRNA in sensory neurons

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