Increased numbers of opioid expressing inflammatory cells do not affect intra-articular morphine analgesia

Abstract

The dose-response relationship of i.a. morphine analgesia is not shifted by enhanced inflammation and END expression within synovial tissue. Thus, the presence of END within inflamed synovial tissue does not seem to interfere with i.a. morphine analgesia.

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

“…The most studied and most successful application is the intra-articular injection of morphine into inflamed knee joints, which has been shown to produce analgesia with efficacy similar to that of local anesthetics or steroids without systemic or local side effects (Stein et al, 1991Khoury et al, 1992;Likar et al, 1997Likar et al, , 1999Likar et al, , 2004. Veterinary trials of intra-articular morphine have demonstrated significant analgesic effects in dogs (Day et al, 1995;Sammarco et al, 1996) and horses (Santos et al, 2009).…”

“…Opioid peptides were detected in human subcutaneous and synovial cells, mast cells, granulocytes, lymphocytes, and macrophages. The prevailing peptides are END and Met-enkephalin, but dynorphin and endomorphins were also found Likar et al, 2004Likar et al, , 2007Heurich et al, 2007;Mousa et al, 2007b;Rittner et al, 2007a;Straub et al, 2008). In patients undergoing knee surgery, blockade of intra-articular opioid receptors by the local administration of naloxone resulted in significantly increased postoperative pain .…”

“…In addition, CRF receptors are coexpressed with END in synovial inflammatory cells, and the intra-articular application of CRF can transiently reduce postoperative pain (Likar et al, 2007). Apparently, endogenous immune cell-derived opioids do not interfere with exogenous agonists, because intraarticular morphine is an equally potent analgesic in patients with and without opioid-producing inflammatory synovial cells Likar et al, 2004). In line with our animal studies, this indicates that immune cell-derived opioids do not produce cross-tolerance to exogenous opioid agonists, but may, in fact, prevent the development of tolerance at peripheral opioid receptors (Zöllner et al, 2008).…”

“…It has not been thoroughly examined whether combinations of opioids (e.g., endogenous opioid peptides and exogenous opioids) interact in a synergistic fashion in peripheral injured tissue, although initial studies have provided some evidence Likar et al, 2004;Schramm and Honda, 2010). The effect of coapplied END or Met-enkephalin with exogenous opioids could be investigated in animals or patients with painful diseases showing minor leukocyte infiltration, e.g., in osteoarthritis.…”

Blockade of intra-articular adrenergic receptors increases analgesic demands for pain relief after knee surgery

“…Previous clinical studies have shown that endogenous opioid peptides are expressed in inflamed synovial tissue and that pain following knee surgery can be effectively controlled through the activation of intra-articular (i.a.) opioid receptors on peripheral terminals of sensory neurons [3][4][5]. Animal and in vitro experiments have shown that adrenergic agonists can release opioid peptides from inflammatory cells and give rise to local analgesic effects resulting from decreased electrical excitability of sensory neurons and/or reduced release of proinflammatory neuropeptides [2,6].…”