Opioid receptors and opioid peptide-producing leukocytes in inflammatory pain – Basic and therapeutic aspects

  title={Opioid receptors and opioid peptide-producing leukocytes in inflammatory pain – Basic and therapeutic aspects},
  author={Melanie Busch-Dienstfertig and Christoph Stein},
  journal={Brain, Behavior, and Immunity},
Mechanisms of Expression and Release of Endogenous Opioids in Peripheral Tissues
There are reasons to believe that the clinical use of peripherally acting opioids can help one to substantially avoid the negative side effects caused by the action of conventional analgesics (opioids and anticonvulsants).
Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy
Future aims include the development of peripherally restricted opioid agonists, selective targeting of opioid-containing immune cells to sites of painful injury, and the augmentation of peripheral ligand and receptor synthesis.
Targeting peripheral opioid receptors to promote analgesic and anti-inflammatory actions
The role of opioids in peripheral inflammatory conditions and the clinical implications of targeting peripheral opioid receptors are focused on.
Dual Peripheral Actions of Immune Cells in Neuropathic Pain
  • H. Machelska
  • Biology, Medicine
    Archivum Immunologiae et Therapiae Experimentalis
  • 2010
This review analyzes both detrimental and advantageous actions of leukocytes at peripheral nerves in neuropathic pain and indicates that targeting opioid-containing immune cells might represent a new disease-modifying approach based on the use of beneficial effects of neuro-inflammation in painful neuropathies.
Targeting inflammation and wound healing by opioids.
Cutaneous Opioid Receptors and Stress Responses: Molecular Interactions and Opportunities for Therapeutic Intervention
Findings on the cutaneous opioid system concerning the treatment of skin pain, itching, wound healing, homeostasis, and ageing will be discussed and open opportunities for medical and cosmetic applications will be suggested.
Bidirectional Regulation of Opioid and Chemokine Function
  • T. Rogers
  • Biology, Medicine
    Frontiers in Immunology
  • 2020
The opioid family of GPCRs consists of the classical opioid receptors, designated μ-, κ-, and δ-opioid receptors, and the orphanin-FQ receptor, and these proteins are expressed on both neuronal and


Peripheral mechanisms of pain and analgesia
Immune cell-derived opioids protect against neuropathic pain in mice.
It is demonstrated that leukocytes containing opioids are essential regulators of pain in a mouse model of neuropathy, and selective targeting of opioid-containing immune cells promotes endogenous pain control and offers novel opportunities for management of painful neuropathies.
Peripheral mechanisms of opioid analgesia.
Modulation of Peripheral Endogenous Opioid Analgesia by Central Afferent Blockade
These findings suggest an interplay of central and peripheral mechanisms of pain control and an effective central inhibition of pain apparently signals a reduced need for recruitment of opioid-containing immune cells to injured sites.
Neurokinin-1 Receptor Antagonists Inhibit the Recruitment of Opioid-containing Leukocytes and Impair Peripheral Antinociception
Endogenous inhibition of inflammatory pain is dependent on NK1 receptor–mediated recruitment of opioid-containing leukocytes and stress-induced antinociception.
Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue.
In vivo and in vitro findings suggest that IL-1 and CRF activate their receptors on immune cells to release opioids that subsequently occupy multiple opioid receptors on sensory nerves and result in antinociception.
Rapid Modulation of μ-Opioid Receptor Signaling in Primary Sensory Neurons
The results indicate that μ-opioid receptor signaling in primary sensory TG neurons is enhanced by activation of phospholipase C-coupled receptors via a cyclooxygenase-dependent AA metabolite that is downstream of PKC.
Opioid Peptide–expressing Leukocytes: Identification, Recruitment, and Simultaneously Increasing Inhibition of Inflammatory Pain
The degree of endogenous pain inhibition is proportional to the number of opioid peptide–producing cells, and distinct leukocyte lineages contribute to this function at different stages of inflammation.