naloxone and Neurogenic-Inflammation

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 (P<0.05, ANOVA). (ii) Opioid-containing leukocytes in the paw and CRF-induced antinociception were reduced after PMN depletion (P<0.05, t-test). (iii) Opioid-containing leukocytes mostly expressed CXCR2. MIP-2 and KC, but not CINC-2 were detectable in inflamed but not in noninflamed tissue (P<0.05, ANOVA). (iv) Combined but not single blockade of MIP-2 and KC reduced the number of opioid-containing leukocytes and peripheral opioid-mediated antinociception (P<0.05, t-test; P>0.05, ANOVA). In summary, in early inflammation peripheral opioid-mediated antinociception is critically dependent on PMN and their recruitment by CXCR2 chemokines.

Topics: Analysis of Variance; Animals; Antibodies; Cell Count; Cell Movement; Chemokine CXCL2; Chemokines; Chemokines, CXC; Corticotropin-Releasing Hormone; Dose-Response Relationship, Drug; Drug Administration Routes; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Freund's Adjuvant; Gene Expression Regulation; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Male; Naloxone; Narcotics; Neurogenic Inflammation; Neutrophils; Pain; Pain Management; Pain Measurement; Pain Threshold; Rats; Rats, Wistar; Receptors, Interleukin-8B

It is believed that acupunctural stimulation induces an analgesic response mainly through a central mechanism: that is, through an increase in the production of opioid peptides and their release at different levels in the nervous system. We sought to establish whether the modulating effect of acupuncture on experimental neurogenic edema can be attributed to a central mechanism only or whether a peripheral mechanism could also exist. Intraperitoneal administration was compared to local administration in the same paw in rats that were injected with capsaicin and in the same dermatome of the acupunctural stimulation.. Experimentation was conducted on 105 male Sprague-Dawley rats weighing 180-220 g, divided into 7 groups as follows: group 1, control; groups 2-4 (15 animals), stimulated with manual acupuncture; group 3 also treated with intraperitoneal naloxone 1 mg/kg; group 4 also treated locally with naloxone (20 microg); groups 5-7 (15 animals), stimulated with 5 Hz and 5 mA electroacupuncture (EAP); group 6 also treated with intraperitoneal naloxone, 1 mg/kg, group 7 also treated locally with naloxone (20 microg).. The results indicate that the administration of 1 mg/kg of naloxone intraperitoneally can inhibit the modulating effect of acupunctural stimulation. Equally effective in inhibiting the modulating effect of acupunctural stimulation, although not having a systemic effect, is a 20-microg dose of naloxone administered peripherally on the site of edema induction.. It is possible to conclude that both systemic and peripheral mechanisms seem to be implicated in the modulating effect of acupuncture on the neurogenic inflammation mechanism.

Topics: Animals; Capsaicin; Edema; Electroacupuncture; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Naloxone; Narcotic Antagonists; Neurogenic Inflammation; Random Allocation; Rats; Rats, Sprague-Dawley; Single-Blind Method

Neurogenic inflammation is mediated via sensory peptides released from the peripheral terminals of sensory nerves and can be modulated by locally released opioid peptides at the site of injury. Endomorphins are recently discovered endogenous opioid peptides with high selectivity and affinity for the mu-opioid receptor. The aim of this study was to examine the ability of endomorphin-1 (EM-1) to modulate the inflammatory response under different injury conditions.. A vacuum-induced blister model in anaesthetised rats (nembutal 60 mg/kg i.p.) was used to examine the effect of EM-1 on the acute inflammatory response induced by; (1) electrical stimulation (ES) of the distal portion of the exposed/cut sciatic nerve at 20 V, 5 Hz, 2 ms for 1 min or; (2) superfusion of substance P (SP) over the blister base. In addition, the effect of EM-1 on the inflammatory response to SP was examined under acute, recurrent (repeated blister induction) and chronic (chronic sciatic nerve lesion) injury conditions.. Prior and concomitant perfusion of EM-1 (100 microM) significantly inhibited the vascular response to ES by 58% compared to controls. EM-1 also inhibited the inflammatory response to SP (both vasodilatation and plasma extravasation) in a dose-dependent manner. Significant inhibition was achieved at 100 microM and 1 mM concentrations of EM-1. Naloxone (1 mg/kg i.v.) reversed the inhibitory effect of EM-1 on the inflammatory response to SP. EM-1 (100 microM) was equally potent in inhibiting the inflammatory response to SP under acute (34% inhibition) recurrent (39%) and chronic (42%) injury conditions.. The current results demonstrate a greater inhibitory effect of EM-1 on the inflammatory response to electrical nerve stimulation (58% inhibition) compared to SP (34% inhibition) suggesting the involvement of both pre- and post-terminal mechanisms in the inhibitory modulatory actions of EM-1. Evidence is provided for the involvement of opioid receptors in this inhibitory effect. The results also suggest that EM-1 is equipotent in inhibiting the inflammatory response under different injury conditions.

Topics: Administration, Topical; Analgesics, Opioid; Animals; Blister; Blood Flow Velocity; Electric Stimulation; Male; Naloxone; Neurogenic Inflammation; Oligopeptides; Plasma; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Sciatic Nerve; Skin Diseases, Vesiculobullous; Substance P; Vasodilation