Peripheral analgesic and antiinflammatory effects of opioids

Abstract

Traditionally, opioids were considered the prototype of centrally acting analgesics. In the past decade a substantial literature has emerged demonstrating that opioids can produce potent and clinically measurable analgesia by activation of opioid receptors on peripheral terminals of primary sensory neurons. In addition, endogenous ligands of these peripheral receptors were discovered in immune cells. Major recent findings in peripheral opioid analgesia include the relative lack of tolerance under inflammatory conditions, tetrapeptides as novel peripherally restricted compounds, the potent antiinflammatory activity of mu- and kappa-agonists and the identification of selectins as important molecules governing the homing of opioid cells to injured tissue. In addition to the extensively documented efficacy of locally applied morphine in post-surgical pain, clinical studies have now moved into the field of chronic arthritic pain.

Tolerance to the Antinociceptive and Antiexudative Effects of Morphine in a Murine Model of Peripheral Inflammation

“…However, even at these dose levels, we could clearly discriminate the effects of s.c. morphine in the different experimental conditions. Doses of morphine that induced antinociception also produced inhibition of plasma extravasation with a biphasic response that has been reported previously by our group and others (Stein et al, 2001a;Romero et al, 2005). The dual response could be related to high-and low-affinity states of the MOR or to different functional subtypes or splice variants of the receptors (Pasternak, 2001).…”

Nebulized Morphine as a Treatment for Dyspnea in a Child With Cystic Fibrosis

“…10 Although there is a ceiling effect on the degree of analgesia attainable with the peripheral administration of opioids, benefits of this route include the anti-inflammatory effects of and agonists and a lack of tolerance under conditions of inflammation. 11 One study suggested the receptor to be the predominant opioid receptor found in the lung. 12 An additional mechanism for the therapeutic effects of inhaled morphine might be the inhibition of pulmonary-irritant receptors.…”

Loss of Peripheral Morphine Analgesia Contributes to the Reduced Effectiveness of Systemic Morphine in Neuropathic Pain

“…In addition to the supraspinal and spinal localization, opioid receptors have been found in peripheral nerves, and peripherally injected opiates produce potent analgesia in acute pain models (Coggeshall et al, 1997;Dionne et al, 2001;Stein et al, 2001). Peripheral morphine is reported to have potent antinociceptive effect under inflammatory conditions (Stein et al, 1988).…”