Lumbar intrathecal naloxone blocks analgesia produced by microstimulation of the ventromedial medulla in the rat

Zorman, Greg; Belcher, G.; Adams, John E.; Fields, Howard L.

doi:10.1016/0006-8993(82)90035-x

Cited by 120 publications

(34 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the idea that opioids cannot activate opioid receptors unless peptidases are inhibited conflicts with studies showing that intrathecal injections of opioid antagonists block the analgesia produced by stimulation of the periaqueductal gray or the rostro-ventral medulla (Jensen and Yaksh, 1984;Morgan et al, 1991;Zorman et al, 1982), or by noxious stimuli (Tambeli et al, 2003). Indeed, it seems futile to release of opioids if they are going to be degraded by peptidases before they can activate their receptors.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

et al. 2008

View full text Add to dashboard Cite

The internalization of μ-opioid receptors (MORs) provides an ideal way to locate areas of opioid peptide release. We used this method to study opioid release in the spinal cord evoked by noxious stimuli in anesthetized rats. Previous studies have shown that opioids released in the spinal cord produce MOR internalization only when they are protected from peptidase degradation. Accordingly, rats were implanted with chronic intrathecal catheters that were used to inject a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) onto the lumbar spinal cord. Five minutes later, a noxious stimulus was delivered to the paw. Lumbar spinal segments were double-stained with antibodies against MORs and neurokinin 1 receptors (NK1Rs) using immunofluorescence. Mechanical stimulation of the hindpaw consisted of repeated 10 sec clamps with a hemostat for 10 min. In the ipsilateral dorsal horn, the stimulus produced abundant NK1R internalization in segments L3-L6, and a more modest but significant MOR internalization in segments L5 and L6. In the contralateral dorsal horn, NK1R was substantially lower and MOR internalization was negligible. The same mechanical stimulus applied to a forepaw did not produce NK1R or MOR internalization in the lumbar spinal cord. Thermal stimulation consisted of immersing a hindpaw in water at 52 °C for 2 min. It produced substantial NK1R internalization ipsilaterally in segment L6, but no MOR internalization. These results show that mechanical stimulation induces segmental opioid release, i.e., in the dorsal horn receiving the noxious signals and not in other spinal segments.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Opioid receptors in the spinal cord play a key role in pain modulation (Budai and Fields, 1998;Jensen and Yaksh, 1984;Morgan et al, 1991;Zorman et al, 1982). However, little is known about the neuronal circuitry in the spinal cord that drives the release of endogenous opioid peptides (henceforth "opioids").…”

Section: Introductionmentioning

confidence: 99%

Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The analgesic effect of serotonin is reported to be mediated from periaqueductal grey (PAG), NRM, and serotonergic receptors present in the spinal dorsal horn [75]. The spinal release of opioid may be driven by a serotonergic descending pathway [76–78] and is at least in part elicited by activation of 5-HT 3 receptors [79]. The electrolytic lesion of the NRM, a procedure known to decrease the release of 5-HT in the spinal cord [80], attenuates EA-induced analgesia [81].…”

Section: Endogenous Opioids and Descending Inhibitory Systemmentioning

confidence: 99%

Mechanisms of Electroacupuncture-Induced Analgesia on Neuropathic Pain in Animal Model

Kim

Min

2013

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Neuropathic pain remains as one of the most difficult clinical pain syndromes to treat. Electroacupuncture (EA), involving endogenous opioids and neurotransmitters in the central nervous system (CNS), is reported to be clinically efficacious in various fields of pain. Although multiple experimental articles were conducted to assess the effect of EA-induced analgesia, no review has been published to assess the efficacy and clarify the mechanism of EA on neuropathic pain. To this aim, this study was firstly designed to evaluate the EA-induced analgesic effect on neuropathic pain and secondly to guide and help future efforts to advance the neuropathic pain treatment. For this purpose, articles referring to the analgesic effect of acupuncture on neuropathic pain and particularly the work performed in our own laboratory were analyzed. Based on the articles reviewed, the role of spinal opioidergic, adrenergic, serotonergic, cholinergic, and GABAergic receptors in the mechanism of EA-induced analgesia was studied. The results of this research demonstrate that μ and δ opioid receptors, α 2-adrenoreceptors, 5-HT1A and 5-HT3 serotonergic receptors, M1 muscarinic receptors, and GABAA and GABAB GABAergic receptors are involved in the mechanisms of EA-induced analgesia on neuropathic pain.

show abstract

“…volume was 5–10 μl of drug followed by a 10 μl saline flush (Zorman et al, 1982, Jensen and Yaksh, 1984, Aimone et al, 1987, Kondo et al, 2005). These volumes predominantly distribute the drug throughout the spinal cord but not the brain (Yaksh and Rudy, 1976, Chen et al, 2007).…”

Section: 0 Materials and Methodsmentioning

confidence: 99%

Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons

Taylor

Kuphal

et al. 2014

Neuroscience

View full text Add to dashboard Cite

Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in microdialysate of the dorsal horn. NPY also decreased non-noxious stimulus (paw brush)-evoked NK1R internalization (as well as mechanical hyperalgesia and mechanical and cold allodynia) after intraplantar injection of carrageenan. Similarly, in rat spinal cord slices with dorsal root attached, [Leu31, Pro34]-NPY inhibited dorsal root stimulus-evoked NK1R internalization. In rat dorsal root ganglion neurons, Y1 receptors colocalized extensively with calcitonin gene-related peptide (CGRP). In dorsal horn neurons, Y1 receptors were extensively expressed and this may have masked detection of terminal co-localization with CGRP or SP. To determine whether the pain inhibitory actions of Y1 receptors are enhanced by inflammation, we administered [Leu31, Pro34]-NPY after intraplantar injection of complete Freund's adjuvant (CFA) in rat. We found that [Leu31, Pro34]-NPY reduced paw clamp-induced NK1R internalization in CFA rats but not uninjured controls. To determine the contribution of increased Y1 receptor-G protein coupling, we measured [35S]GTPγS binding simulated by [Leu31, Pro34]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception.

show abstract

Lumbar intrathecal naloxone blocks analgesia produced by microstimulation of the ventromedial medulla in the rat

Cited by 120 publications

References 30 publications

Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

Mechanisms of Electroacupuncture-Induced Analgesia on Neuropathic Pain in Animal Model

Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons

Contact Info

Product

Resources

About