Control of inflammatory pain by chemokine-mediated recruitment of opioid-containing polymorphonuclear cells
Male; Pain Measurement; Analysis of Variance; Animals; Rats; Non-U.S. Gov't; Research Support; Comparative Study; Dose-Response Relationship; Drug; Receptors; Naloxone/pharmacology; Freund's Adjuvant; Wistar; Flow Cytometry/methods; Antibodies/pharmacology; Cell Count/methods; Cell Movement/physiology; Chemokines; Chemokines/immunology/physiology; Corticotropin-Releasing Hormone/therapeutic use; CXC/immunology/metabolism; Drug Administration Routes; Enzyme-Linked Immunosorbent Assay/methods; Gene Expression Regulation/physiology; Immunohistochemistry/methods; Intercellular Signaling Peptides and Proteins/immunology/metabolism; Interleukin-8B/metabolism; Narcotics/metabolism; Neurogenic Inflammation/chemically induced/complications/therapy; Neutrophils/metabolism; Pain Threshold/drug effects; Pain/etiology/therapy
Opioid-containing leukocytes can counteract inflammatory hyperalgesia. Under stress or after local injection of corticotropin releasing factor (CRF), opioid peptides are released from leukocytes, bind to opioid receptors on peripheral sensory neurons and mediate antinociception. Since polymorphonuclear cells (PMN) are the predominant opioid-containing leukocyte subpopulation in early inflammation, we hypothesized that PMN and their recruitment by chemokines are important for peripheral opioid-mediated antinociception at this stage. Rats were intraplantarly injected with complete Freund's adjuvant (CFA). Using flow cytometry, immunohistochemistry, and ELISA, leukocyte subpopulations, chemokine receptor (CXCR2) expression on opioid-containing leukocytes and the CXCR2 ligands keratinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant-2 (CINC-2) were quantified. Paw pressure threshold (PPT) was determined before and after intraplantar and subcutaneous injection of CRF with or without naloxone. PMN depletion was achieved by intravenous injection of an antiserum. Chemokines were blocked by intraplantar injection of anti-MIP-2 and/or anti-KC antiserum. We found that at 2 h post CFA (i) intraplantar but not subcutaneous injection of CRF produced dose-dependent and naloxone-reversible antinociception (P0.05, ANOVA). In summary, in early inflammation peripheral opioid-mediated antinociception is critically dependent on PMN and their recruitment by CXCR2 chemokines.
2004
Brack A; Rittner HL; Machelska H; Leder K; Mousa SA; Schafer M; Stein C
Pain
2004
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/j.pain.2004.08.029" target="_blank" rel="noreferrer">10.1016/j.pain.2004.08.029</a>
Peripheral opioid receptors mediating antinociception in inflammation. Activation by endogenous opioids and role of the pituitary-adrenal axis
Male; Analysis of Variance; Animals; Rats; Biomarkers of Pain; Dose-Response Relationship; Drug; Receptors; Naloxone/pharmacology; Foot; Biomarkers Reference List; Adrenalectomy; Cold; Endorphins/physiology; Hypophysectomy; Inbred Strains; Inflammation/physiopathology; Naltrexone/pharmacology; Nociceptors/physiopathology; Opioid/physiology; Pituitary-Adrenal System/physiology; Stress/physiopathology; Swimming
This study investigated the involvement of endogenous opioid peptides in mediating cold water swim (CWS) stress-induced antinociception (SIA) in rats with unilateral hind paw inflammation induced by Freund's complete adjuvant (FCA). Following 0.5, 1 and 2 min of CWS, there was a duration-dependent elevation of paw pressure threshold (PPT) in both inflamed and non-inflamed paws which was maximal immediately after CWS and returned to control values within 15 min. The antinociception elicited in the inflamed paw was significantly greater than that elicited in the non-inflamed paw. The antinociception induced by a 1 min CWS was dose dependently antagonized by tertiary naloxone (0.125-1 mg/kg s.c.) and completely reversed by tertiary naltrexone (0.5 mg/kg). Quaternary naltrexone (5-40 mg/kg s.c.) was similarly effective in reversing the elevation of inflamed PPT induced by a 1 min CWS stress. In contrast, similar doses of quaternary naltrexone had no effect against centrally mediated morphine antinociception in non-inoculated rats. Adrenalectomy was without effect on the pattern of SIA seen in FCA-treated rats. Surgical hypophysectomy completely abolished the differential antinociception induced by 0.5 and 1 min durations of CWS but had little effect on that following 2 min of CWS stress. Inhibition of hypophysial corticotrophic cell secretion with dexamethasone (300 micrograms/kg) injected s.c. 120 min prior to CWS completely abolished the differential SIA at all durations of CWS tested. beta-Endorphin 12.5 micrograms/kg administered i.v. in non-stressed rats also caused a greater elevation of PPT in inflamed than in non-inflamed paws. This effect was not reversed by concomitant i.v. administration of (-) tertiary naloxone 5 mg/kg or quaternary naltrexone 20 mg/kg.
1990
Parsons CG; Czlonkowski A; Stein C; Herz A
Pain
1990
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/0304-3959(90)91112-v" target="_blank" rel="noreferrer">10.1016/0304-3959(90)91112-v</a>
Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue
Humans; Male; Analysis of Variance; Animals; Regression Analysis; Rats; Biomarkers of Pain; Injections; Dose-Response Relationship; Drug; Naloxone/pharmacology; Enkephalin; Inflammation/immunology/physiopathology; Wistar; Antibodies/pharmacology; beta-Endorphin/immunology/physiology; Corticotropin-Releasing Hormone/administration & dosage/pharmacology/therapeutic use; Cyclosporine/pharmacology; Dynorphins/immunology/physiology; Endorphins/immunology/physiology/secretion; Interleukin-1/administration & dosage/pharmacology/therapeutic use; Leucine/analogs & derivatives/pharmacology; Methionine/immunology/physiology; Pain/immunology/physiopathology/prevention & control; Recombinant Proteins/pharmacology/therapeutic use; Somatostatin/analogs & derivatives/pharmacology
Local analgesic effects of exogenous opioid agonists are particularly prominent in painful inflammatory conditions and are mediated by opioid receptors on peripheral sensory nerves. The endogenous ligands of these receptors, opioid peptides, have been demonstrated in resident immune cells within inflamed tissue of animals and humans. Here we examine in vivo and in vitro whether interleukin 1 beta (IL-1) or corticotropin-releasing factor (CRF) is capable of releasing these endogenous opioids and inhibiting pain. When injected into inflamed rat paws (but not intravenously), IL-1 and CRF produce antinociception, which is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively, and by the immunosuppressant cyclosporine A. In vivo administration of antibodies against opioid peptides indicates that the effects of IL-1 and CRF are mediated by beta-endorphin and, in addition, by dynorphin A and [Met]enkephalin, respectively. Correspondingly, IL-1 effects are inhibited by mu-, delta-, and kappa-opioid antagonists, whereas CRF effects are attenuated by all except a kappa-antagonist. Finally, IL-1 and CRF produce acute release of immunoreactive beta-endorphin in cell suspensions freshly prepared from inflamed lymph nodes. This effect is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively. These 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. beta-Endorphin, mu- and delta-opioid receptors play a major role, but IL-1 and CRF appear to differentially release additional opioid peptides.
1994
Schafer M; Carter L; Stein C
Proceedings Of The National Academy Of Sciences Of The United States Of America
1994
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1073/pnas.91.10.4219" target="_blank" rel="noreferrer">10.1073/pnas.91.10.4219</a>
What do plasma beta-endorphin levels reveal about endogenous opioid analgesic function?
Female; Humans; Male; Adult; Middle Aged; Double-Blind Method; Cross-Over Studies; beta-Endorphin/blood; Biomarkers of Pain; Acute Pain/blood/physiopathology; Analgesia/methods; Chronic Pain/blood/physiopathology; Low Back Pain/blood/physiopathology; Naloxone/pharmacology; Narcotic Antagonists/pharmacology; Pain Measurement/drug effects; Pain Threshold/drug effects/physiology; Physical Stimulation
Bruehl S; Burns JW; Chung OY; Chont M
European Journal Of Pain
2012
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1002/j.1532-2149.2011.00021.x" target="_blank" rel="noreferrer">10.1002/j.1532-2149.2011.00021.x</a>