scholarly journals Peripherally-Acting Opioids

2008 ◽  
Vol 2s;11 (3;2s) ◽  
pp. S121-S132
Author(s):  
Howard Smith
Keyword(s):  
Spinal Cord ◽  
Adverse Effects ◽  
Opioid Receptors ◽  
Opioid Analgesic ◽  
Opioid Analgesics ◽  
Endogenous Opioids ◽  
Term Therapy ◽  
Endogenous Opioid ◽  
Key Words Pain ◽  
The Brain

Opioids are broad-spectrum analgesics with potent pain-relieving qualities but also with potential adverse effects related to both short-term and long-term therapy. Researchers have attempted to alter existing opioid analgesics, utilize different routes/ formulations, or combine opioid analgesics with other compounds in efforts to improve analgesia while minimizing adverse effects. Exogenous opioids, administered in efforts to achieve analgesia, work by mimicking the actions of endogenous opioids. Endogenous opioids and their receptors are located in the brain (supraspinal areas), spinal cord, and periphery. Although opioids and opioid receptors in the brain and spinal cord have received much attention over many years, peripheral endogenous opioid analgesic systems have only been extensively studied during the past decade. It has been known since 1990 that following injection into the rodent hindpaw, d-Ala2 , N-Me-Phe4 , Gly5 -ol-enkephalin (DAMGO) [a muopioid receptor agonist] probably exerts its antinociceptive effects locally, since the doses administered are too low to have an effect in the central nervous system (CNS). This notion has been supported by the observation that the quaternary compound morphine methyliodide, which does not as readily cross the bloodbrain barrier and enter the CNS, produced antinociception following intradermal administration into the hindpaw, but not when the same dose was administered systemically (subcutaneously at a distant site). With a growing appreciation of peripheral endogenous opioids, peripheral endogenous opioid receptors, and peripheral endogenous opioid analgesic systems, investigators began growing hopeful that it may be possible to achieve adequate analgesics while avoiding unwanted central untoward adverse effects (e.g. respiratory depression, somnolence, addiction). Peripherally-acting opioids, which capitalize on peripheral endogenous opioid analgesic systems, may be one potential future strategy which may be utilized in efforts to achieve potent analgesia with minimal side effects. Key words: Pain, opioids, immune cells, peripherally-acting opioids (PAO), leukocytes, inflammatory pain, peripheral analgesia

CHOICE AND ROUTE OF OPIOIDS FOR ANALGESIA DURING LABOUR

2005 ◽  
Vol 16 (4) ◽  
pp. 281-288
Author(s):  
DONALD H PENNING
Keyword(s):  
Spinal Cord ◽  
Opioid Receptors ◽  
Epidural Space ◽  
Pain Control ◽  
Substantia Gelatinosa ◽  
Endogenous Opioid ◽  
Opioid Ligands ◽  
Pain Transmission ◽  
The Brain

Reports in the 1970's by Snyder and others of opioid receptors in the brain and the substantia gelatinosa of the spinal cord triggered a search for endogenous opioid ligands (β-endorphin and the encephalin peptides) which might modify pain transmission. It was not long after that morphine was administered into the human epidural space for pain control, including obstetric patients.

scholarly journals Combination Opioid Analgesics

2008 ◽  
Vol 2;11 (3;2) ◽  
pp. 201-214
Author(s):  
Howard Smith
Keyword(s):  
Adverse Effects ◽  
Opioid Analgesic ◽  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Active Metabolites ◽  
Analgesic Tolerance ◽  
Key Words Pain ◽  
Long Duration ◽  
Wide Range ◽  
Opioid Induced Hyperalgesia

Although there is no “ideal analgesic,” scientists and clinicians alike continue to search for compounds with qualities which may approach the “ideal analgesic.” Characteristics of an “ideal” analgesic may include: the agent is a full agonist providing optimal/maximal analgesia for a wide range/variety of pain states (e.g., broad spectrum analgesic activity), it does not exhibit tolerance, it produces no unwanted effects and minimal adverse effects, it has no addictive potential, it does not facilitate pain/hyperalgesia, it has a long duration, it has high oral bioavailability, it is not vulnerable to important drug interactions, it is not significantly bound to plasma proteins, it has no active metabolites, it has linear kinetics, and it is eliminated partly by hydrolysis to an inactive metabolite (without involvement of oxidative and conjugative enzymes). Investigators have concentrated on ways to alter existing analgesics or to combine existing analgesic compounds with compounds which may improve efficacy over time or minimize adverse effects. The addition of an analgesic with a second agent (which may or may not also be an analgesic) to achieve a “combination analgesic” is a concept which has been exploited for many years. Although there may be many reasons to add 2 agents together in efforts to achieve analgesia, for purposes of this article — reasons for combining an opioid with a second agent to produce a combination opioid analgesic may be classified into 6 major categories: 1.) combinations to prolong analgesic duration; 2.) combinations to enhance or optimize analgesic efficacy (e.g., analgesic synergy); 3.) combinations to diminish or minimize adverse effects; 4.) combinations to diminish opioid effects which are not beneficial (or contrariwise to or enhance beneficial opioid effects); 5.) combinations to reduce opioid tolerance/opioid-induced hyperalgesia; and 6.) combinations to combat dependency issues/addiction potential/craving sensations. Combination opioid analgesics are one avenue which may give rise to “pain pills” with improved analgesic profiles over existing analgesic medications. Key words: Pain, combination opioid analgesic, tolerance, opioid-induced hyperalgesia

Effects of naloxone on the sensation of dyspnea during acute respiratory stress in normal adults

1993 ◽  
Vol 74 (2) ◽  
pp. 590-595 ◽  
Author(s):  
Y. Akiyama ◽  
M. Nishimura ◽  
S. Kobayashi ◽  
A. Yoshioka ◽  
M. Yamamoto ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Endogenous Opioids ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Specific Effects ◽  
Mouth Pressure ◽  
End Tidal ◽  
Visual Analogue Scaling ◽  
The Brain ◽  
Normal Adults

To clarify whether endogenous opioids modulate the dyspnea intensity and, if so, by what mechanism they act on it, we examined 12 healthy male volunteers aged 19–27 yr for ventilatory and peak mouth pressure (Pm) responses to hypoxic progressive hypercapnia with inspiratory flow-resistive loading after the intravenous infusion of 3 mg of naloxone or saline. The intensity of dyspnea was simultaneously assessed by visual analogue scaling every 15 s. Naloxone administration increased both ventilatory and Pm responses to hypoxic progressive hypercapnia (P < 0.05 for both). The increase in dyspnea intensity for a given increase in end-tidal PCO2 was significantly greater after naloxone infusion than after saline (P < 0.05). However, there were no differences in the increase in dyspnea intensity for a given increase in minute ventilation or Pm. These results suggest that the endogenous opioid system suppresses the respiratory output under a strong, acute respiratory stress in normal adults and that this system may relieve the dyspnea sensation secondary to the suppression of the brain stem respiratory center without specific effects on the processing of respiratory sensations in the higher brain.

scholarly journals Relationship Between Endogenous Opioid Function and Opioid Analgesic Adverse Effects

2014 ◽  
Vol 39 (3) ◽  
pp. 219-224 ◽  
Author(s):  
Rajnish K. Gupta ◽  
Stephen Bruehl ◽  
John W. Burns ◽  
Asokumar Buvanendran ◽  
Melissa Chont ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Opioid Analgesic ◽  
Endogenous Opioid

scholarly journals Harnessing endogenous opioids for pain relief: Fantasy vs reality

2020 ◽  
Vol 16 (1) ◽  
pp. 67-72
Author(s):  
Alan R. Gintzler, PhD ◽  
Nai-Jiang Liu, MD, PhD
Keyword(s):  
Pain Relief ◽  
Opioid Analgesic ◽  
Endogenous Opioids ◽  
Opioid Analgesia ◽  
Opioid Overdose ◽  
Endogenous Opioid ◽  
Current Crisis ◽  
Novel Approach ◽  
Clinical Pain ◽  
Opioid Antinociception

Objective: To review evidence demonstrating efficacy and feasibility of harnessing the activity of endogenous opioid analgesic systems for pain management.Methods: The authors sought to summarize a wealth of data that establish proof of concept that the analgesic activity of endogenous opioids can be exploited to clinically benefit from the enormous pain-relieving abilities of these peptides without contributing to the current crisis of death by synthetic opioid overdose.Results: There is a plethora of studies demonstrating that not only can endogenous opioids mediate placebo-induced antinociception but they are also active in modulating clinical pain. Earlier studies convincingly demonstrate the effectiveness of psychological strategies to coopt endogenous opioid analgesic systems to produce pain relief. The challenge is to define pharmacological targets for activating endogenous opioid analgesia reliably in a clinical setting. Based on insights gleaned from mechanisms underlying the ebb and flow of analgesic responsiveness to the spinal application of endomorphin 2, multiple signaling proteins were identified that activate endogenous spinal opioid analgesia. Notably, this was achieved in the absence of any exogenous synthetic opioid.Conclusions: Utilization of drugs that harness endogenous opioid antinociception in accordance with varying physiological states represents a novel approach for effective pain management while mitigating the present epidemic of death by synthetic opioid overdose.

scholarly journals Peripherally Acting Opioids in Orofacial Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Qing Liu ◽  
Hongwen He ◽  
Lijia Mai ◽  
Shengyan Yang ◽  
Wenguo Fan ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Orofacial Pain ◽  
Immune Cell ◽  
Region Growing ◽  
Endogenous Opioids ◽  
Cellular Mechanisms ◽  
Endogenous Opioid ◽  
Peripheral Tissues ◽  
Analgesic Effects ◽  
Peripheral Opioid Receptors

The activation of opioid receptors by exogenous or endogenous opioids can produce significant analgesic effects in peripheral tissues. Numerous researchers have demonstrated the expression of peripheral opioid receptors (PORs) and endogenous opioid peptides (EOPs) in the orofacial region. Growing evidence has shown the involvement of PORs and immune cell-derived EOPs in the modulation of orofacial pain. In this review, we discuss the role of PORs and EOPs in orofacial pain and the possible cellular mechanisms involved. Furthermore, the potential development of therapeutic strategies for orofacial pain is also summarized.

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.

Role of mu 1- and delta-opioid receptors in modulation of fetal EEG and respiratory activity

1993 ◽  
Vol 265 (2) ◽  
pp. R433-R438 ◽  
Author(s):  
P. Y. Cheng ◽  
D. Wu ◽  
Y. Soong ◽  
S. McCabe ◽  
J. A. Decena ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Respiratory Activity ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Receptor Subtypes ◽  
Endogenous Opioid ◽  
Eeg Activity ◽  
Delta Opioid Receptors ◽  
Opioid Receptor Subtypes

Recent evidence suggests that administration of low doses of morphine causes respiratory stimulation, along with a more active electroencephalogram (EEG) in the fetal lamb. The present study used selective opioid agonists and antagonists to determine the role mu 1- and delta-opioid receptor subtypes play in the response as well as determine if endogenous opioid peptides exert a tonic influence at the mu 1- and delta-opioid receptors to maintain normal EEG and respiratory activity under control, physiological conditions. Both morphine (2.5 mg/h iv) and [D-Pen2,D-Pen5]enkephalin (DPDPE) (46 nmol/h icv) resulted in a significant activation of fetal EEG, which was blocked by naloxonazine (NALZ, mu 1-opioid antagonist) and naltrindole (NTI, delta-opioid antagonist), respectively. Administration of NALZ alone, but not NTI, resulted in a slowing of the EEG. Morphine and [D-Ala2]deltorphin I (0.36 nmol/h icv) significantly increased breath number and were blocked by NALZ and NTI respectively. Both NALZ and NTI alone resulted in a reduction in breath number. These results suggest that the activation of the delta- or mu 1-opioid receptors will stimulate fetal respiratory and EEG activity. Furthermore, the endogenous opioids play a tonic role at both the delta- and mu 1-opioid receptors in the regulation of respiratory timing and EEG activity.

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