Peripheral analgesia: mechanism of the analgesic action of aspirin‐like drugs and opiate‐antagonists.

Abstract

1 Prostaglandins released by tissue injury sensitize nociceptors and produce hyperalgesia. 2 Aspirin‐like drugs inhibit prostaglandins I2 and E2, synthesis, which explains their anti‐algic effect. 3 The anti‐ algic effect of aspirin‐like drugs in carrageenin‐induced rat paw inflammation may involve a central component. 4 Prostaglandin E2‐ induced hyperalgesia, once established, is not relieved by systemically administered drugs. 5 Prostaglandin‐induced hyperalgesia is possibly a cyclic adenosine, 3′,5′‐monophosphate C2+ dependent process. 6 Morphine, enkephalins, opiate antagonists and cyclic guanosine 3′,5′‐ monophosphate have a peripheral analgesic effect in the prostaglandin hyperalgesia test. 7 Morphine may produce peripheral analgesia by inhibiting adenylatecyclase activity at the nociceptors.

Local Loperamide Inhibits Thermal Hyperalgesia But Not Mechanical Allodynia Induced by Intratibial Inoculation of Melanoma Cells in Mice

“…Furthermore, the expression of these receptors on peripheral nociceptive fibers explains the analgesia that opioids induce when acting at the periphery (Coggeshall et al 1997;Truong et al 2003). The analgesic efficacy of opioids at peripheral level has been mainly proven in experimental settings related to inflammation (Ferreira 1980;Stein et al 2003), although peripheral opioid antihyperalgesic effects have also been described in a model of murine osteosarcoma-induced hyperalgesia induced by intraosteal administration of NCTC 2472 cells (Menéndez et al 2003b(Menéndez et al , 2005(Menéndez et al , 2007Baamonde et al 2005). Data obtained by studying this model of osteosarcoma in mice seem to indicate that some nociceptive symptoms evoked by bone cancer may be inhibited by the stimulation of peripheral opioid receptors.…”

Anti-Hyperalgesic Effects of Meloxicam Hydrogel via Phonophoresis in Acute Inflammation in Rats; Comparing Systemic and Topical Application

“…Meloxicam is a selective COX-2 inhibitor (Xin et al, 2007), which mediates its anti-hyperalgesic effect (Abramson and Weissmann, 1989;Francischi et al, 2002). Nociceptors are sensitized whenever the major COX-like prostaglandins are isolated from the inflammatory sites (Cesare and McNaughton, 1997;Chen et al, 1999), which cause hyperalgesia (Ferreira, 1980). Meloxicam hydrogel produced similar or better effects than anti-inflammatory drugs using other administration routes (Dirig et al, 1998;Jett et al, 1999;Feltenstein et al, 2004).…”

Role of peripheral μ‐opioid receptors in arthritis: Are they potential targets for therapy?

“…The existence of opioid receptors outside the central nervous system and opioid-induced analgesia generated by these peripheral receptors was first reported more than 30 years ago by Ferreira and colleagues (5). Recently, an increasing number of reports have supported this possibility (2)(3)(4)6).…”