scholarly journals Peripherally Acting Opioids and Clinical Implications for Pain Control

2011 ◽  
Vol 3;14 (3;5) ◽  
pp. 249-258
Author(s):  
Nalini Sehgal
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Opioid Receptors ◽  
Opioid Peptides ◽  
Nerve Fibers ◽  
Dorsal Root Ganglion Neurons ◽  
Opioid Agonists ◽  
Anti Inflammatory ◽  
Peripheral Opioid Receptors ◽  
Ganglion Neurons

Opioid receptors are widely expressed in the central and peripheral nervous system and in the non-neuronal tissues. Data from animal and human clinical studies support the involvement of peripheral opioid receptors in analgesia, especially in the presence of inflammation. Inflammation has been shown to increase the synthesis of opioid receptors in the dorsal root ganglion neurons and enhance transport and accumulation of opioid receptors in the peripheral terminals of sensory neurons. Under the influence of chemokines and adhesion molecules, opioid peptide-containing immune cells extravasate and accumulate in the injured tissues. Stress, chemokines, cytokines, and other releasing factors in inflamed tissues stimulate these granulocytes to release opioid peptides. Once secreted, opioid peptides bind to and activate peripheral opioid receptors on sensory nerve fibers and produce analgesia by decreasing the excitability of sensory nerves and/or inhibiting release of pro-inflammatory neuropeptides. Research has revealed that local application of exogenous opioid agonists produces a potent analgesic effect by activating peripheral opioid receptors in inflamed tissues. The analgesic activity occurs without activation of opioid receptors in the central nervous system (CNS), and therefore centrally mediated side effects, such as respiratory depression, mental clouding, altered consciousness, or addiction, are not associated with peripheral opioid activity. This discovery has stimulated research on developing peripherally restricted opioid agonists that lack CNS effects. In addition, it has been recognized that opioid receptors modulate inflammation, and that opioids have antiinflammatory effects. The anti-inflammatory actions of opioids are not well known or understood. Conflicting reports on mu-opioids suggest both anti-inflammatory and pro-inflammatory effects. This article will present the basis for peripheral opioid analgesia and describe current research directed at developing novel treatments for pain with improved side effect profiles. Key words: Opioids, opioid receptors, opioid agonists, peripheral nervous system, peripheral opioid receptors

scholarly journals 3D in vitro peripheral nervous system organoid using mouse primary dorsal root ganglion neurons and Schwann cells

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S124
Author(s):  
Woon-Hae Kim ◽  
Hyun-Gyu Kang ◽  
Taehoon H. Kim ◽  
Yoon Jeong Mo ◽  
Yu Seon Kim ◽  
...  
Keyword(s):  
Nervous System ◽  
Dorsal Root Ganglion ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

scholarly journals Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

2013 ◽  
Vol 305 (1) ◽  
pp. H76-H85 ◽  
Author(s):  
Liang-Wu Fu ◽  
John C. Longhurst
Keyword(s):  
Myocardial Ischemia ◽  
Opioid Receptors ◽  
Opioid Peptides ◽  
Nerve Fibers ◽  
Afferent Nerve ◽  
Nerve Activity ◽  
Afferent Nerves ◽  
Peripheral Opioid Receptors ◽  
Cardiac Afferents

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP ( n = 7) or bradykinin ( n = 7). These data suggest that peripheral opioid peptides suppress the responses of cardiac sympathetic afferent nerves to myocardial ischemia and ischemic mediators like ATP and bradykinin.

EVIDENCE FOR A CENTRAL OPIOID CONTROL OF RUMINATION

1984 ◽  
Vol 64 (5) ◽  
pp. 13-15 ◽  
Author(s):  
Y. RUCKEBUSCH ◽  
TH. BARDON
Keyword(s):  
Key Words ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Opioid Peptides ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Receptor Agonists ◽  
Opioid Agonists ◽  
Reflex Control ◽  
Opioid Receptor Agonists

Intravenous adrenaline induced reticular extracontractions and rumination within 26 sec in hay-fed, and 184 sec in cube-fed sheep. Regardless of diet, pretreatment with cerebroventricular infusion of kappa-opioid-receptor agonists enhanced this reflex. Control of rumination may involve multiple opioid-receptors, since inhibition of the reflex occurred after mu- and delta-opioid-agonists. Key words: Sheep, rumination, opioid-peptides

Intracellular calcium recordings from isolated cells of the mammalian central nervous system

1987 ◽  
Vol 65 (5) ◽  
pp. 926-933 ◽  
Author(s):  
M. E. Morris ◽  
J. F. MacDonald ◽  
J. J. Friedlich ◽  
I. Szekelyhidi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Intracellular Calcium ◽  
Mouse Embryo ◽  
Dorsal Root Ganglion Neurons ◽  
Brain Cells ◽  
Isolated Cells ◽  
Mammalian Central Nervous System ◽  
Intracellular Ca ◽  
Ganglion Neurons

Measurements made with two different techniques of intracellular calcium levels from small isolated cells of the mammalian central nervous system are described and compared. Recordings in cultured mouse embryo spinal cord and dorsal root ganglion neurons, made with double-barrelled borosilicate Ca2+-selective microelectrodes yielded a mean Ca2+ level of 2.3 (SE ± 0.54) μM for the lowest values recorded in 24 out of 46 cells. Intracellular Ca2+ dependence on membrane potential was apparent with levels of calcium ≥4 μM (r = 0.371, n = 29). Both cyclic fluctuations induced by tetraethylammonium and an apparent increase in Ca2+ evoked by the depolarizing excitatory amino acid, L-aspartate, were observed. In contrast, estimates of intracellular Ca2+ obtained by spectrofluorimetry of suspensions of mouse embryo brain cells, loaded with the intracellular Ca-binding fluorescent probe, quin2 provided a [Formula: see text]-fold lower value, 152 (SE ± 7) nM. This more closely resembles levels reported for large neurons where large-tip microelectrodes with greater sensitivity were used, and in spite of the heterogeneity of the cells this value is presumed to be a more accurate estimate of intraneuronal Ca2+ concentration. In these fluorescence studies KCl readily evoked increases in intracellular Ca2+ which could be blocked by verapamil and Cd2+ and were not induced in the absence of Ca2+. Increases were also produced by N-methyl-D-aspartate, but not by the kainate-like Lathyrus neurotoxin, L-3-oxalylamino-2-aminopropionic acid. These results provide preliminary evidence for both voltage-sensitive and receptor-activated Ca channels in embryonic brain cells. Although the recording of intraneuronal Ca2+ with conventional ion-selective microelectrodes in small cells has problems with respect to accuracy, stability, and time constant, recent advances in the design of Ca2+ sensors and electrodes are promising. These, as well as developments in techniques of single cell fluorescence analysis, now offer methods with improved and powerful capacity for accurate and simultaneous measurements of intracellular Ca2+ and membrane electrophysiological parameters.

scholarly journals Sampling and Evaluating the Peripheral Nervous System

2019 ◽  
Vol 48 (1) ◽  
pp. 10-18 ◽  
Author(s):  
Mark T. Butt
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Sciatic Nerve ◽  
Peripheral Nervous System ◽  
Morphological Changes ◽  
Sampling Strategy ◽  
Mechanisms Of Toxicity ◽  
Test Article ◽  
Ganglion Neurons ◽  
The Brain

Many preclinical investigations limit the evaluation of the peripheral nervous system (PNS) to paraffin-embedded sections/hematoxylin and eosin–stained sections of the sciatic nerve. This limitation ignores several key mechanisms of toxicity and anatomic differences that may interfere with an accurate assessment of test article effects on the neurons/neurites peripheral to the brain and spinal cord. Ganglion neurons may be exposed to higher concentrations of the test article as compared to neurons in the brain or spinal cord due to differences in capillary permeability. Many peripheral neuropathies are length-dependent, meaning distal nerves may show morphological changes before they are evident in the mid-sciatic nerve. Paraffin-embedded nerves are not optimal to assess myelin changes, notably those leading to demyelination. Differentiating between axonal or myelin degeneration may not be possible from the examination of paraffin-embedded sections. A sampling strategy more consistent with known mechanisms of toxicity, atraumatic harvest of tissues, optimized fixation, and the use of resin and paraffin-embedded sections will greatly enhance the pathologist’s ability to observe and characterize effects in the PNS.

scholarly journals Distribution of functional opioid receptors in human dorsal root ganglion neurons

Pain ◽  
2020 ◽  
Vol 161 (7) ◽  
pp. 1636-1649 ◽  
Author(s):  
Jamie K. Moy ◽  
Jane E. Hartung ◽  
Melissa G. Duque ◽  
Rob Friedman ◽  
Vidhya Nagarajan ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Opioid Receptors ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

The Anti-Inflammatory and Antinociceptive Properties of the Chloroform Fraction FromPhyllanthus niruriPlant Is Mediated via the Peripheral Nervous System

2010 ◽  
Vol 7 (4) ◽  
pp. 341-350 ◽  
Author(s):  
Ifeoma Chinwude Obidike ◽  
Oluwakanyinsola Adeola Salawu ◽  
Mary Ndukuba ◽  
Charles Ogbonnaya Okoli ◽  
Uche Alex Osunkwo
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Chloroform Fraction ◽  
Anti Inflammatory
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