Endogenous opioids mediate stress-induced analgesia

2018 ◽  
Author(s):  
Claudia Sommer
Keyword(s):  
Opioid Receptors ◽  
Immune Cells ◽  
Endogenous Opioids ◽  
Sensory Nerves ◽  
Opioid Analgesia ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
First Time ◽  
Endogenous Analgesia

This chapter reviews the landmark paper published in 1990 by Stein et al. and entitled ‘Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation’. Opioids, besides acting centrally as analgesics, may act peripherally upon opioid receptors located on axons and on immune cells. In the publication by Stein et al., it was shown for the first time that endogenous opioid peptides released from immune cells mediate stress-induced analgesia, potentially through opioid receptors on peripheral nerve endings. This finding has led to numerous follow-up studies on endogenous analgesia, including work showing that cannabinoid analgesia is mediated via the peripheral release of opioids, and to the concept of topical opioid analgesia, which may be a good way of using the potent analgesia that opioids can convey, without their CNS-associated side effects.

Modulation of Peripheral Endogenous Opioid Analgesia by Central Afferent Blockade

2003 ◽  
Vol 98 (1) ◽  
pp. 195-202 ◽  
Author(s):  
Thomas K. Schmitt ◽  
Shaaban A. Mousa ◽  
Alexander Brack ◽  
Diego K. Schmidt ◽  
Heike L. Rittner ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Cells ◽  
Cold Water ◽  
Intrathecal Morphine ◽  
Opioid Analgesia ◽  
Endogenous Opioid ◽  
Freund’S Complete Adjuvant ◽  
Freund's Complete Adjuvant ◽  
Pressure Threshold ◽  
Endogenous Analgesia

Background Peripheral tissue injury causes a migration of opioid peptide-containing immune cells to the inflamed site. The subsequent release and action of these peptides on opioid receptors localized on peripheral sensory nerve terminals causes endogenous analgesia. The spinal application of opioid drugs blocks the transmission of nociceptive information from peripheral injury. This study investigates the influence of exogenous spinal opioid analgesia on peripheral endogenous opioid analgesia. Methods Six and forty-eight hours after initiation of continuous intrathecal morphine infusion and administration of Freund's complete adjuvant into the hind paw of rats, antinociceptive and antiinflammatory effects were measured by paw pressure threshold, paw volume, and paw temperature, respectively. Inflammation and quantity of opioid-containing cells were evaluated by immunocytochemistry and flow cytometry. Cold water swim stress-induced endogenous analgesia was examined 24 h after discontinuation of intrathecal morphine administration. Results Intrathecal morphine (10 micro g/h) resulted in a significant and stable increase of paw pressure threshold ( P< 0.05) without changing inflammation, as evaluated by paw volume, paw temperature, and flow cytometry ( P> 0.05). At 48 but not at 6 h after Freund's complete adjuvant, the number of beta-endorphin-containing cells and cold water swim-induced antinociception were significantly reduced in intrathecal morphine-treated rats compared with those treated with intrathecal vehicle ( P< 0.05). Conclusions These findings suggest an interplay of central and peripheral mechanisms of pain control. An effective central inhibition of pain apparently signals a reduced need for recruitment of opioid-containing immune cells to injured sites.

Met5-enkephalin protects isolated adult rabbit cardiomyocytes via δ-opioid receptors

1999 ◽  
Vol 277 (6) ◽  
pp. H2442-H2450 ◽  
Author(s):  
Yasushi Takasaki ◽  
Roger A. Wolff ◽  
Grace L. Chien ◽  
Donna M. van Winkle
Keyword(s):  
Cell Death ◽  
Opioid Receptors ◽  
Ischemic Preconditioning ◽  
Opioid Peptides ◽  
Trypan Blue ◽  
Adult Rabbit ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Simulated Ischemia ◽  
Hypoxic Incubation

In rats and rabbits, endogenous opioid peptides participate in ischemic preconditioning. However, it is not known which endogenous opioid(s) can trigger cardioprotection. We examined preconditioning-induced and opioid-induced limitation of cell death in isolated, calcium-tolerant, adult rabbit cardiomyocytes. Cells were subjected to simulated ischemia by pelleting and normothermic hypoxic incubation. Preconditioning was elicited with 15 min of simulated ischemia followed by 15 min of resuspension and reoxygenation. All cells underwent 180 min of simulated ischemia. Cell death was assessed by trypan blue permeability. Morphine protected cells, as did preconditioning; naloxone blocked the preconditioning-induced protection. Exogenous Met5-enkephalin (ME) induced protection, but exogenous β-endorphin did not. ME-induced protection was blocked by the δ-selective antagonist naltrindole. Additionally, two other proenkephalin products, Leu5-enkephalin and Met5-enkephalin-Arg-Phe, provided protection equipotent to ME. These data suggest that one or more proenkephalin products interact with δ-opioid receptors to endogenously trigger opioid-mediated protection.

Novel peripheral mechanisms of opioid analgesia

1997 ◽  
Vol 20 (3) ◽  
pp. 465-466
Author(s):  
Christoph Stein ◽  
Michael Schäfer
Keyword(s):  
Cell Proliferation ◽  
Side Effects ◽  
Opioid Peptides ◽  
Immune Cell ◽  
Opioid Analgesia ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Injury Site ◽  
Underlying Mechanisms ◽  
Peripheral Opioid Receptors

dickenson briefly mentions that peripheral opioid receptors somehow become active following inflammation and that the appearance of endogenous opioid peptides at the injury site may be related to immune cell proliferation. Recent findings elucidate the underlying mechanisms in more detail and provide an incentive for the development of a novel generation of analgesics devoid of typical central opioid side effects.

Endogenous opioids and ventilatory responses to hypercapnia in normal humans

1985 ◽  
Vol 58 (5) ◽  
pp. 1415-1420 ◽  
Author(s):  
S. E. Weinberger ◽  
R. A. Steinbrook ◽  
D. B. Carr ◽  
E. R. von Gal ◽  
J. E. Fisher ◽  
...  
Keyword(s):  
Opioid Peptides ◽  
Endogenous Opioids ◽  
Opiate Antagonist ◽  
Endogenous Opioid Peptides ◽  
Short Term ◽  
Endogenous Opioid ◽  
Beta Endorphin ◽  
Ventilatory Responses ◽  
Normal Humans

Though administration of opioid peptides depresses ventilation and ventilatory responsiveness, the role of endogenous opioid peptides in modulating ventilatory responsiveness is not clear. We studied the interaction of endogenous opioids and ventilatory responses in 12 adult male volunteers by relating hypercapnic responsiveness to plasma levels of immunoactive beta-endorphin and by administering the opiate antagonist naloxone. Ventilatory responsiveness to hypercapnia was not altered by pretreatment with naloxone, and this by itself suggests that endogenous opioids have no role in modulating this response. However, there was an inverse relationship between basal levels of immunoactive beta-endorphin in plasma and ventilatory responsiveness to CO2. Furthermore, plasma beta-endorphin levels rose after short-term hypercapnia but only when subjects had been pretreated with naloxone. We conclude that measurement of plasma endorphin levels suggests relationships between endogenous opioid peptides and ventilatory responses to CO2 that are not apparent in studies limited to assessing the effect of naloxone.

scholarly journals Sigma-1 receptors control immune-driven peripheral opioid analgesia during inflammation in mice

2017 ◽  
Vol 114 (31) ◽  
pp. 8396-8401 ◽  
Author(s):  
Miguel A. Tejada ◽  
Angeles Montilla-García ◽  
Shane J. Cronin ◽  
Domagoj Cikes ◽  
Cristina Sánchez-Fernández ◽  
...  
Keyword(s):  
Immune Cells ◽  
Thermal Hyperalgesia ◽  
Opioid Analgesia ◽  
Endogenous Opioid ◽  
Drug Induced ◽  
Immune Infiltrate ◽  
Pathophysiological Role ◽  
Sigma 1 ◽  
Peripheral Opioid Analgesia

Sigma-1 antagonism potentiates the antinociceptive effects of opioid drugs, so sigma-1 receptors constitute a biological brake to opioid drug-induced analgesia. The pathophysiological role of this process is unknown. We aimed to investigate whether sigma-1 antagonism reduces inflammatory pain through the disinhibition of the endogenous opioidergic system in mice. The selective sigma-1 antagonists BD-1063 and S1RA abolished mechanical and thermal hyperalgesia in mice with carrageenan-induced acute (3 h) inflammation. Sigma-1–mediated antihyperalgesia was reversed by the opioid antagonists naloxone and naloxone methiodide (a peripherally restricted naloxone analog) and by local administration at the inflamed site of monoclonal antibody 3-E7, which recognizes the pan-opioid sequence Tyr–Gly–Gly–Phe at the N terminus of most endogenous opioid peptides (EOPs). Neutrophils expressed pro-opiomelanocortin, the precursor of β-endorphin (a known EOP), and constituted the majority of the acute immune infiltrate. β-endorphin levels increased in the inflamed paw, and this increase and the antihyperalgesic effects of sigma-1 antagonism were abolished by reducing the neutrophil load with in vivo administration of an anti-Ly6G antibody. The opioid-dependent sigma-1 antihyperalgesic effects were preserved 5 d after carrageenan administration, where macrophages/monocytes were found to express pro-opiomelanocortin and to now constitute the majority of the immune infiltrate. These results suggest that immune cells harboring EOPs are needed for the antihyperalgesic effects of sigma-1 antagonism during inflammation. In conclusion, sigma-1 receptors curtail immune-driven peripheral opioid analgesia, and sigma-1 antagonism produces local opioid analgesia by enhancing the action of EOPs of immune origin, maximizing the analgesic potential of immune cells that naturally accumulate in painful inflamed areas.

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