The Effects of pH on Beta-Endorphin and Morphine Inhibition of Calcium Transients in Dorsal Root Ganglion Neurons

Vetter, Irina; Kapitzke, Daniel; Hermanussen, Siobhan; Monteith, Gregory R.; Cabot, Peter J.

doi:10.1016/j.jpain.2006.01.456

Cited by 28 publications

(18 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The later stages have shown to have an increased role for peripheral opioid antinociception (Labuz et al, 2006, 2007). In the periphery, immune cells have been demonstrated to contain and release the opioid peptide β-endorphin in inflamed tissues which then acts upon opioid receptors present on primary afferent neurons to block pain transmission and thus provide analgesia (Mousa et al, 2000; Vetter et al, 2006). Labuz et al (2006) demonstrated that treatment of inflamed tissue with anti-β-endorphin antibody attenuated endogenous antinociceptive effects in this tissue.…”

Section: Role Of Endogenous Opioid Systems In Inflammationmentioning

confidence: 99%

“…The rate of metabolic degradation of opioid peptides is increased in inflamed tissues (Vetter et al, 2006; Schreiter et al, 2012). Release of inflammatory factors such as hydrogen ions from damaged cells, cytokines and chemokines from resident cells and peptidases from immune and neuronal cells create a hostile environment that acts to quickly break down opioids (Vetter et al, 2006; Schreiter et al, 2012).…”

Section: The Effect Of Inflammatory Conditions On Opioid Efficacymentioning

confidence: 99%

“…Release of inflammatory factors such as hydrogen ions from damaged cells, cytokines and chemokines from resident cells and peptidases from immune and neuronal cells create a hostile environment that acts to quickly break down opioids (Vetter et al, 2006; Schreiter et al, 2012). In order for opioid peptides to reach their receptors on nociceptive primary afferent neurons, interaction between neurons and immune cells may be required.…”

Section: The Effect Of Inflammatory Conditions On Opioid Efficacymentioning

confidence: 99%

See 2 more Smart Citations

Targeting peripheral opioid receptors to promote analgesic and anti-inflammatory actions

2013

View full text Add to dashboard Cite

Mechanisms of endogenous pain control are significant. Increasing studies have clearly produced evidence for the clinical usefulness of opioids in peripheral analgesia. The immune system uses mechanisms of cell migration not only to fight pathogens but also to control pain and inflammation within injured tissue. It has been demonstrated that peripheral inflammatory pain can be effectively controlled by an interaction of immune cell-derived opioid peptides with opioid receptors on peripheral sensory nerve terminals. Experimental and clinical studies have clearly shown that activation of peripheral opioid receptors with exogenous opioid agonists and endogenous opioid peptides are able to produce significant analgesic and anti-inflammatory effects, without central opioid mediated side effects (e.g., respiratory depression, sedation, tolerance, dependence). This article will focus on the role of opioids in peripheral inflammatory conditions and the clinical implications of targeting peripheral opioid receptors.

show abstract

Section: Role Of Endogenous Opioid Systems In Inflammationmentioning

confidence: 99%

Section: The Effect Of Inflammatory Conditions On Opioid Efficacymentioning

confidence: 99%

Section: The Effect Of Inflammatory Conditions On Opioid Efficacymentioning

confidence: 99%

See 1 more Smart Citation

Targeting peripheral opioid receptors to promote analgesic and anti-inflammatory actions

2013

View full text Add to dashboard Cite

show abstract

“…Inflammation is also accompanied by a sprouting of opioid receptorbearing peripheral sensory nerve terminals and by a disrupted perineural barrier facilitating the access of opioid agonists to their receptors (Antonijevic et al, 1995;Rittner et al, 2009b). In addition, low extracellular pH increases opioid agonist efficacy, presumably by altering the interaction of opioid receptors with G proteins and adenylyl cyclase (Rasenick and Childers, 1989;Selley et al, 1993;Vetter et al, 2006). Under conditions of elevated cAMP/protein kinase A activity (as seen in inflammation), morphine can inhibit TRPV1 translocation to the plasma membrane, which may lead to reduced neuronal excitability (Vetter et al, 2008).…”

mentioning

confidence: 99%

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

2011

View full text Add to dashboard Cite

“…Furthermore, the release of protons in inflamed tissue, resulting in lower pH values in the inflamed site is associated with the increased efficacy of opioid agonist due to decreased inactivation of G-proteins in neuronal membranes in vitro as demonstrated previously (169). This is in line with the latter finding, showing that acidic environment contributes towards the increased in opioid efficacy at the injured site (170).…”

Section: Opioid-induced Peripheral Analgesiasupporting

confidence: 88%

The immunomodulation of dynorphin 1-17 and its biotransformation fragments on inflammatory signalling pathways

Rahiman¹,

Sarah²

View full text Add to dashboard Cite

Inflammation is a complex physiological process that involves host defense mechanisms in response to the intrusion of harmful external stimuli. Uncoordinated inflammatory responses, however, are the underlying pathophysiological cause of many chronic diseases. Inflammation is characterised by the burgeoning migration of leukocytes to the point of injury and subsequent release of pro-nociceptive mediators, generating inflammatory pain. Dynorphin 1-17 (DYN 1-17) is endogenously produced and released from leukocytes upon stimulation by local inflammatory factors in the inflamed area. This opioid peptide primarily binds to kappa-opioid receptor (KOR) to produce analgesia. Under inflammatory milieu, DYN 1-17 undergoes spontaneous degradation, yielding a variety of opioid and non-opioid fragments that may have significant implications in inflammation. The underlying cellular effects of these fragments remain unclear. This thesis seeks to explore potential mechanistic insights into selected major DYN 1-17 fragments, identified from a previous biotransformation study of DYN 1-17 in rodent inflamed tissue. This thesis examines the DYN 1-17 fragments modulation of intracellular signals associated with inflammation and thereby, gain an insight into novel therapeutic targets through exploring these endogenous mechanisms.Utilising THP-1 macrophages as an in vitro model of inflammation, this thesis begins with a semiquantitative assessment of nuclear factor-kappa B/p65 (NF-κB/p65) translocation, a major transcription factor that regulates genes responsible for immune and inflammatory responses. The findings presented in Chapter Three of this thesis demonstrated that DYN 1-17 and selected major fragments (DYN 1-6, 1-7, 1-9, 1-10, 1-11, 3-14, 6-12, 2-17 and 7-17) significantly attenuated NF-κB/p65 nuclear translocation induced by lipopolysaccharide (LPS), with the greatest reduction observed with DYN 1-7 at 10 nM. A selective KOR antagonist, ML-190, was used to examine KOR involvement in this inhibitory action. ML-190 significantly reversed the inhibition of NF-κB/p65 translocation produced by DYN 1-17, DYN 1-6, DYN 1-7 and DYN 1-9, but not DYN 1-10 and DYN 1-11.Cytokine production is linked as a downstream process to NF-κB activation; hence it is necessary to evaluate the ability of DYN 1-17 and selected biotransformation fragments in the modulation of IL-1β and TNF-α release in differentiated THP-1 cells, as presented in Chapter Four, to gain an insight into the effects on major pro-inflammatory cytokines. DYN 1-17 and the fragments, demonstrated differential modulatory effects on LPS-induced release of IL-1β and TNF-α. DYN 1-7 and DYN 1-6, inhibited and elevated the secretion of both cytokines, respectively, in a concentration-dependent manner (10 -11 to 10 -7 M). DYN 1-17, however, only inhibited IL-1β release from differentiated iii THP-1 cells and had no effect on TNF-α secretion. Intriguingly, DYN 3-14 at 10 -17 to 10 -11 M demonstrated significant inhibition on IL-1β release and paradoxically increased TNF-α lev...

show abstract

The Effects of pH on Beta-Endorphin and Morphine Inhibition of Calcium Transients in Dorsal Root Ganglion Neurons

Cited by 28 publications

References 66 publications

Targeting peripheral opioid receptors to promote analgesic and anti-inflammatory actions

Targeting peripheral opioid receptors to promote analgesic and anti-inflammatory actions

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

The immunomodulation of dynorphin 1-17 and its biotransformation fragments on inflammatory signalling pathways

Contact Info

Product

Resources

About