Reduction of ??-Endorphin-Containing Immune Cells in Inflamed Paw Tissue Corresponds with a Reduction in Immune-Derived Antinociception: Reversible by Donor Activated Lymphocytes

Abstract

The immune system not only contributes to inflammation, but also provides localized analgesia. A depleted immune system results in a reduction of immune-derived analgesia and a potentiation of inflammatory pain. Donor activated lymphocytes reverse these effects, highlighting the importance of a functional immune system in inflammatory pain.

Peripheral Antinociceptive Effects of Exogenous and Immune Cell-Derived Endomorphins in Prolonged Inflammatory Pain

“…This indicates that leukocytes are the source of opioids producing both forms of antinociception and is in line with previous studies (Schäfer et al, 1994;Hermanussen et al, 2004;Machelska et al, 2004). Importantly, both stress-and CRF-induced antinociception was dose dependently attenuated by pretreatment with Abs against EM-1 and EM-2.…”

Endogenous Opioid-Mediated Analgesia Is Dependent on Adaptive T Cell Response in Mice

“…The production of opioids has been described in most of the hematopoietic cells (4,14,18,19), but our results, in line with others (5,11,12), suggest that effector memory T lymphocytes are more efficient to relieve inflammatory pain. These results suggesting that the potency of immune cells to produce opioids is probably not similar have been testified by quantifying the relative ability of the main cellular components of the adaptive immune response to synthesize all three opioid precursors.…”

“…Within the first 96 h of inflammation, leukocyte-mediated analgesia is only observed following injection of triggering factors including IL-1b (5), corticotrophin-releasing factor (1, 5), noradrenaline (6), chemotactic factors (7,8), and thrombin receptor ligands (9), or exposure to stress such as cold water swim (2,10). Among immune cells infiltrating the inflammatory site, memory T lymphocytes have been described to be more efficient to relieve pain (5,11,12). These findings showing that stimulation of opioid-producing immune cells within inflamed tissues may downmodulate pain perception led us to investigate endogenous regulation of inflammatory pain in the context of adaptive T cell immune response.…”

Quantitation of Doxorubicin Uptake, Efflux, and Modulation of Multidrug Resistance (MDR) in MDR Human Cancer Cells

“…The final concentration of dimethyl sulfoxide in the treated cells was less than 0.1%. Cyclosporine A and PSC833 were also dissolved in the vehicle of 7:3 sterile water to 95% ethanol for animal injections (Hermanussen et al, 2004).…”