title: Involvement of the peripheral sensory and sympathetic nervous system in the vascular endothelial expression of ICAM-1 and the recruitment of opioid-containing immune cells to inhibit inflammatory pain.
abstract: Endogenous opioids are known to be released within certain brain areas following stressful stimuli. Recently, it was shown that also leukocytes are a potential source of endogenously released opioid peptides following stress. They activate sensory neuron opioid receptors and result in the inhibition of local inflammatory pain. An important prerequisite for the recruitment of such leukocytes is the expression of intracellular adhesion molecule-1 (ICAM-1) in blood vessels of inflamed tissue. Here, we investigated the contribution of peripheral sensory and/or sympathetic nerves to the enhanced expression of ICAM-1 simultaneously with the increased recruitment of opioid peptide-containing leukocytes to promote the inhibition of inflammatory pain. Selective degeneration of either peripheral sensory or sympathetic nerve fibers by their respective neurotoxins, capsaicin or 6-hydroxydopamime, significantly reduced the subcutaneous immigration of β-endorphin- (END-) and met-enkephalin- (ENK-)-containing polymorphonuclear leukocytes (PMN) (in the early phase) and mononuclear cells (in the late phase) during painful Freund's complete adjuvant (FCA) rat hind paw inflammation. In contrast, this treatment did not alter the percentage of opioid peptide-containing leukocytes in the circulation. Calcitonin gene-related peptide- (CGRP-) and tyrosine hydroxylase- (TH-) immunoreactive (IR) nerve fibers were in close contact to ICAM-1 IR blood vessels within inflamed subcutaneous tissue. The selective degeneration of sensory or sympathetic nerve fibers attenuated the enhanced expression of vascular endothelial ICAM-1 after intraplantar (i.pl.) FCA and abolished endogenous opioid peptide-mediated peripheral analgesia. Our results suggest that, during localized inflammatory pain, peripheral sensory and sympathetic nerve fibers augment the expression of vascular endothelial ICAM-1 simultaneously with the increased recruitment of opioid peptide-containing leukocytes which consequently promotes the endogenous opioid peptide-mediated inhibition of inflammatory pain. They support existing evidence about a close link between the nervous and the immune system.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Campus Virchow Klinikum and Campus Charite Mitte, Berlin, Germany. shaaban.mousa@charite.de
authors.forename: Shaaban A
authors.initials: SA
authors.lastname: Mousa
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shaqura
authors.forename: Ute
authors.initials: U
authors.lastname: Brendl
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Khrasani
authors.forename: Susanna
authors.initials: S
authors.lastname: Fürst
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfer
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis; D002211:Capsaicin / Q000494:pharmacology; D004723:Endorphins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005434:Flow Cytometry; D005620:Freund's Adjuvant; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D017933:Peripheral Nervous System / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*; D013565:Sympatholytics / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D004723:Endorphins; D013565:Sympatholytics; D018799:Intercellular Adhesion Molecule-1; D016627:Oxidopamine; D005620:Freund's Adjuvant; D014446:Tyrosine 3-Monooxygenase; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin